PHARMACEUTICAL GUIDELINES

tag:blogger.com,1999:blog-8563020669307343167Sun, 01 Mar 2026 20:02:29 +0000Calibration of UV / Visible spectrophotometerCalibration of automatic potentiometric titratorCleaning Validation ProtocolDevelopment of an efficientDifferece between water content and loss on drying (LOD)Difference among calibrationICH GuidelinesPreparation and Standardization of 0.1 M Disodium Edetate (EDTA)Preparation of Buffer SolutionsPreparation of Indicator SolutionsPreparation of Standard SolutionsProcedure for change control in pharmaceuticalsRegulatory GuidelinesResearchSOP OF SOPSampling procedure for purified waterValidation in pharmaceutical manufacturingWHO Guidelinesaldolase-catalyzed process for enantioselective synthesis of statin intermediateskeep watchingscalablevalidation and qualificationPHARMACEUTICAL GUIDELINESUSFDA guidelines, GMP guidelines, WHO guidelines, Schedule M, FDA, European guidelines cleaning validation, process validation, water system validation, ICH guidelines, GMP audut compliance, equipment qualification, Installation Qualification, Operational Qualification, Performance Qualification, Calibration, Validation Protocol, SOPs etc.http://scholarpharma.blogspot.com/noreply@blogger.com (PHARMA GUIDLINES)Blogger30125en-usnoprotectedUSFDA,guidelines,GMP,guidelines,WHO,guidelines,Schedule,M,FDA,European,guidelines,cleaning,validation,process,validation,water,system,validation,ICH,guidelines,GMP,audut,compliance,equipment,qualification,Installation,Qualification,OperationalUSFDA guidelines, GMP guidelines, WHO guidelines, Schedule M, FDA, European guidelines cleaning validation, process validation, water system validation, ICH guidelines, GMP audut compliance, equipment qualification, Installation Qualification, Operational Qualification, Performance Qualification, Calibration, Validation Protocol, SOPsPHARMA GUIDLINESmargipatel02@gmail.commargipatel02@gmail.commargipatel02@gmail.comtag:blogger.com,1999:blog-8563020669307343167.post-1998020315565746075Fri, 21 Feb 2014 10:04:00 +00002014-02-21T02:04:53.518-08:00Chemical kinetics<div dir="ltr" style="text-align: left;" trbidi="on"> <h1 class="firstHeading" id="firstHeading" lang="en" style="text-align: center;"> <span style="background-color: #0b5394;"><span dir="auto"><span style="background-color: #f3f3f3;"><span></span></span><span style="color: #bf9000;"><span style="background-color: white;">Chemical kinetics</span></span></span></span></h1> <table class="metadata plainlinks ambox ambox-style ambox-No_footnotes" role="presentation"> <tbody> <tr> <td class="mbox-image" style="text-align: right;"><br /></td> <td class="mbox-text" style="text-align: right;"><span style="color: #351c75;">                                                                                                    <span style="color: #990000;">   By Miss.Sejal Jethva</span></span></td> </tr> </tbody></table> <table class="metadata plainlinks ambox ambox-content ambox-one_source" role="presentation"> <tbody> <tr> <td class="mbox-image"><br /></td> <td class="mbox-text"><br /></td> </tr> </tbody></table> <div class="thumb tright"> <div class="thumbinner" style="width: 302px;"> <b><a class="image" href="http://en.wikipedia.org/wiki/File:Molecular-collisions.jpg"><img alt="" class="thumbimage" height="100" src="http://upload.wikimedia.org/wikipedia/commons/thumb/4/41/Molecular-collisions.jpg/300px-Molecular-collisions.jpg" width="300" /></a></b> <div class="thumbcaption"> <div class="magnify"> <b><a class="internal" href="http://en.wikipedia.org/wiki/File:Molecular-collisions.jpg" title="Enlarge"><img alt="" height="11" src="http://bits.wikimedia.org/static-1.23wmf13/skins/common/images/magnify-clip.png" width="15" /></a></b></div> <b><a href="http://en.wikipedia.org/wiki/Reaction_rate" title="Reaction rate">Reaction rate</a> tends to increase with <a href="http://en.wikipedia.org/wiki/Concentration" title="Concentration">concentration</a> – a phenomenon explained by <a href="http://en.wikipedia.org/wiki/Collision_theory" title="Collision theory">collision theory</a>.</b></div> </div> </div> <table cellpadding="0" cellspacing="5" class="vertical-navbox nowraplinks hlist" style="background: #f9f9f9; border-spacing: 0.4em 0; border: 1px solid #aaa; clear: right; float: right; font-size: 88%; line-height: 1.4em; margin: 0 0 1.0em 1.0em; padding: 0.2em; text-align: center; width: 22.0em;"> <tbody> <tr> <td class="navbox-title" style="line-height: 1.2em; padding-top: 0.4em;">Part of <a href="http://en.wikipedia.org/wiki/Category:Chemical_engineering" title="Category:Chemical engineering">a series</a> on</td> </tr> <tr> <th class="navbox-title" style="font-size: 145%; line-height: 1.2em; padding-top: 0; padding: 0.2em 0.4em 0.2em;"><a href="http://en.wikipedia.org/wiki/Chemical_engineering" title="Chemical engineering">Chemical Engineering</a></th> </tr> <tr> <td class="" style="font-weight: bold; padding: 0.3em 0.4em 0.3em;"><a href="http://en.wikipedia.org/wiki/History_of_chemical_engineering" title="History of chemical engineering">History of<br /> Chemical Engineering</a></td> </tr> <tr> <th class="navbox-abovebelow" style="padding: 0.1em;">General Concepts</th> </tr> <tr> <td class="" style="padding: 0 0.1em 0.4em;"> <ul> <li><a href="http://en.wikipedia.org/wiki/Chemical_industry" title="Chemical industry">Chemical industry</a></li> <li><a href="http://en.wikipedia.org/wiki/Chemical_engineer" title="Chemical engineer">Chemical engineer</a></li> <li><a href="http://en.wikipedia.org/wiki/Chemical_process" title="Chemical process">Chemical process</a></li> <li><a href="http://en.wikipedia.org/wiki/Unit_operation" title="Unit operation">Unit operations</a></li> <li><strong class="selflink">Chemical kinetics</strong></li> <li><a href="http://en.wikipedia.org/wiki/Transport_phenomena" title="Transport phenomena">Transport phenomena</a></li> </ul> </td> </tr> <tr> <th class="navbox-abovebelow" style="padding: 0.1em;"><a href="http://en.wikipedia.org/wiki/Unit_process" title="Unit process">Unit processes</a></th> </tr> <tr> <td class="" style="padding: 0 0.1em 0.4em;"> <ul> <li><a href="http://en.wikipedia.org/wiki/Chemical_plant" title="Chemical plant">Chemical plant</a></li> <li><a href="http://en.wikipedia.org/wiki/Chemical_reactor" title="Chemical reactor">Chemical reactor</a></li> <li><a href="http://en.wikipedia.org/wiki/Separation_process" title="Separation process">Separation processes</a></li> </ul> </td> </tr> <tr> <th class="navbox-abovebelow" style="padding: 0.1em;">Areas</th> </tr> <tr> <td class="" style="padding: 0 0.1em 0.4em;"> <ul> <li><a href="http://en.wikipedia.org/wiki/Heat_transfer" title="Heat transfer">Heat transfer</a></li> <li><a href="http://en.wikipedia.org/wiki/Mass_transfer" title="Mass transfer">Mass transfer</a></li> <li><a href="http://en.wikipedia.org/wiki/Fluid_dynamics" title="Fluid dynamics">Fluid dynamics</a></li> <li><a href="http://en.wikipedia.org/wiki/Process_design" title="Process design">Process design</a></li> <li><a href="http://en.wikipedia.org/wiki/Chemical_thermodynamics" title="Chemical thermodynamics">Chemical thermodynamics</a></li> <li><a href="http://en.wikipedia.org/wiki/Chemical_reaction_engineering" title="Chemical reaction engineering">Chemical reaction engineering</a></li> <li><a href="http://en.wikipedia.org/wiki/Industrial_control_system" title="Industrial control system">Process control systems</a></li> </ul> </td> </tr> <tr> <th class="navbox-abovebelow" style="padding: 0.1em;">Other</th> </tr> <tr> <td class="" style="padding: 0 0.1em 0.4em;"> <ul> <li><a href="http://en.wikipedia.org/wiki/Outline_of_chemical_engineering" title="Outline of chemical engineering">Outline of chemical engineering</a></li> <li><a href="http://en.wikipedia.org/wiki/Index_of_chemical_engineering_articles" title="Index of chemical engineering articles">Index of chemical engineering articles</a></li> </ul> </td> </tr> <tr> <td class="navbox-abovebelow" style="font-weight: bold; padding: 0.3em 0.4em 0.3em;"><a href="http://en.wikipedia.org/wiki/Category:Chemical_engineering" title="Category:Chemical engineering">Category: Chemical engineering</a></td> </tr> <tr> <td style="font-size: 115%; text-align: right;"> <div class="plainlinks hlist navbar mini"> <ul> <li class="nv-view"><a href="http://en.wikipedia.org/wiki/Template:Chemical_engineering" title="Template:Chemical engineering"><span title="View this template">v</span></a></li> <li class="nv-talk"><a href="http://en.wikipedia.org/wiki/Template_talk:Chemical_engineering" title="Template talk:Chemical engineering"><span title="Discuss this template">t</span></a></li> <li class="nv-edit"><a class="external text" href="http://en.wikipedia.org/w/index.php?title=Template:Chemical_engineering&action=edit"><span title="Edit this template">e</span></a></li> </ul> </div> </td> </tr> </tbody></table> <b>Chemical kinetics</b>, also known as <b>reaction kinetics</b>, is the study of <a href="http://en.wikipedia.org/wiki/Reaction_rate" title="Reaction rate">rates</a> of chemical processes. Chemical kinetics includes investigations of how different experimental conditions can influence the speed of a chemical reaction and yield information about the <a href="http://en.wikipedia.org/wiki/Reaction_mechanism" title="Reaction mechanism">reaction's mechanism</a> and <a href="http://en.wikipedia.org/wiki/Transition_state" title="Transition state">transition states</a>, as well as the construction of mathematical models that can describe the characteristics of a chemical reaction. In 1864, <a href="http://en.wikipedia.org/wiki/Peter_Waage" title="Peter Waage">Peter Waage</a> and <a class="mw-redirect" href="http://en.wikipedia.org/wiki/Cato_Guldberg" title="Cato Guldberg">Cato Guldberg</a> pioneered the development of chemical kinetics by formulating the <a href="http://en.wikipedia.org/wiki/Law_of_mass_action" title="Law of mass action">law of mass action</a>, which states that the speed of a chemical reaction is proportional to the quantity of the reacting substances.<br /> Chemical kinetics deals with the experimental determination of <a href="http://en.wikipedia.org/wiki/Reaction_rate" title="Reaction rate">reaction rates</a> from which <a class="mw-redirect" href="http://en.wikipedia.org/wiki/Rate_law" title="Rate law">rate laws</a> and <a href="http://en.wikipedia.org/wiki/Reaction_rate_constant" title="Reaction rate constant">rate constants</a> are derived. Relatively simple <a class="mw-redirect" href="http://en.wikipedia.org/wiki/Rate_law" title="Rate law">rate laws</a> exist for <a class="mw-redirect" href="http://en.wikipedia.org/wiki/Rate_law#Zero-order_reactions" title="Rate law">zero-order reactions</a> (for which reaction rates are independent of concentration), <a href="http://en.wikipedia.org/wiki/First-order_reaction" title="First-order reaction">first-order reactions</a>, and <a class="mw-redirect" href="http://en.wikipedia.org/wiki/Second-order_reaction" title="Second-order reaction">second-order reactions</a>, and can be derived for others. In consecutive reactions, the <a href="http://en.wikipedia.org/wiki/Rate-determining_step" title="Rate-determining step">rate-determining step</a> often determines the kinetics. In consecutive first-order reactions, a <a href="http://en.wikipedia.org/wiki/Steady_state_%28chemistry%29" title="Steady state (chemistry)">steady state</a> approximation can simplify the <a class="mw-redirect" href="http://en.wikipedia.org/wiki/Rate_law" title="Rate law">rate law</a>. The <a href="http://en.wikipedia.org/wiki/Activation_energy" title="Activation energy">activation energy</a> for a reaction is experimentally determined through the <a href="http://en.wikipedia.org/wiki/Arrhenius_equation" title="Arrhenius equation">Arrhenius equation</a> and the <a href="http://en.wikipedia.org/wiki/Eyring_equation" title="Eyring equation">Eyring equation</a>. The main factors that influence the <a href="http://en.wikipedia.org/wiki/Reaction_rate" title="Reaction rate">reaction rate</a> include: the <a class="mw-redirect" href="http://en.wikipedia.org/wiki/Physical_state" title="Physical state">physical state</a> of the reactants, the <a class="mw-redirect" href="http://en.wikipedia.org/wiki/Concentrations" title="Concentrations">concentrations</a> of the reactants, the <a href="http://en.wikipedia.org/wiki/Temperature" title="Temperature">temperature</a> at which the reaction occurs, and whether or not any <a class="mw-redirect" href="http://en.wikipedia.org/wiki/Catalysts" title="Catalysts">catalysts</a> are present in the reaction.<br /> <div class="toc" id="toc"> <div id="toctitle"> <h2> Contents</h2> </div> <ul> <li class="toclevel-1 tocsection-1"><a href="http://en.wikipedia.org/wiki/Chemical_kinetics#Factors_affecting_reaction_rate"><span class="tocnumber">1</span> <span class="toctext">Factors affecting reaction rate</span></a> <ul> <li class="toclevel-2 tocsection-2"><a href="http://en.wikipedia.org/wiki/Chemical_kinetics#Nature_of_the_reactants"><span class="tocnumber">1.1</span> <span class="toctext">Nature of the reactants</span></a></li> <li class="toclevel-2 tocsection-3"><a href="http://en.wikipedia.org/wiki/Chemical_kinetics#Physical_state"><span class="tocnumber">1.2</span> <span class="toctext">Physical state</span></a></li> <li class="toclevel-2 tocsection-4"><a href="http://en.wikipedia.org/wiki/Chemical_kinetics#Concentration"><span class="tocnumber">1.3</span> <span class="toctext">Concentration</span></a></li> <li class="toclevel-2 tocsection-5"><a href="http://en.wikipedia.org/wiki/Chemical_kinetics#Temperature"><span class="tocnumber">1.4</span> <span class="toctext">Temperature</span></a></li> <li class="toclevel-2 tocsection-6"><a href="http://en.wikipedia.org/wiki/Chemical_kinetics#Catalysts"><span class="tocnumber">1.5</span> <span class="toctext">Catalysts</span></a></li> <li class="toclevel-2 tocsection-7"><a href="http://en.wikipedia.org/wiki/Chemical_kinetics#Pressure"><span class="tocnumber">1.6</span> <span class="toctext">Pressure</span></a></li> </ul> </li> <li class="toclevel-1 tocsection-8"><a href="http://en.wikipedia.org/wiki/Chemical_kinetics#Equilibrium"><span class="tocnumber">2</span> <span class="toctext">Equilibrium</span></a></li> <li class="toclevel-1 tocsection-9"><a href="http://en.wikipedia.org/wiki/Chemical_kinetics#Free_energy"><span class="tocnumber">3</span> <span class="toctext">Free energy</span></a></li> <li class="toclevel-1 tocsection-10"><a href="http://en.wikipedia.org/wiki/Chemical_kinetics#Applications"><span class="tocnumber">4</span> <span class="toctext">Applications</span></a></li> <li class="toclevel-1 tocsection-11"><a href="http://en.wikipedia.org/wiki/Chemical_kinetics#See_also"><span class="tocnumber">5</span> <span class="toctext">See also</span></a></li> <li class="toclevel-1 tocsection-12"><a href="http://en.wikipedia.org/wiki/Chemical_kinetics#References"><span class="tocnumber">6</span> <span class="toctext">References</span></a></li> <li class="toclevel-1 tocsection-13"><a href="http://en.wikipedia.org/wiki/Chemical_kinetics#External_links"><span class="tocnumber">7</span> <span class="toctext">External links</span></a></li> </ul> </div> <h2> <span class="mw-headline" id="Factors_affecting_reaction_rate">Factors affecting reaction rate</span></h2> <h3> <span class="mw-headline" id="Nature_of_the_reactants">Nature of the reactants</span></h3> Depending upon what substances are reacting, the reaction rate varies. Acid/base reactions, the formation of <a class="mw-redirect" href="http://en.wikipedia.org/wiki/Salts" title="Salts">salts</a>, and <a href="http://en.wikipedia.org/wiki/Ion_exchange" title="Ion exchange">ion exchange</a> are fast reactions. When covalent bond formation takes place between the molecules and when large molecules are formed, the reactions tend to be very slow. Nature and strength of bonds in reactant molecules greatly influence the rate of its transformation into products.<br /> <h3> <span class="mw-headline" id="Physical_state">Physical state</span></h3> The <a class="mw-redirect" href="http://en.wikipedia.org/wiki/Physical_state" title="Physical state">physical state</a> (<a href="http://en.wikipedia.org/wiki/Solid" title="Solid">solid</a>, <a href="http://en.wikipedia.org/wiki/Liquid" title="Liquid">liquid</a>, or <a href="http://en.wikipedia.org/wiki/Gas" title="Gas">gas</a>) of a reactant is also an important factor of the rate of change. When reactants are in the same <a href="http://en.wikipedia.org/wiki/Phase_%28matter%29" title="Phase (matter)">phase</a>, as in <a class="mw-redirect" href="http://en.wikipedia.org/wiki/Aqueous" title="Aqueous">aqueous</a> <a href="http://en.wikipedia.org/wiki/Solution" title="Solution">solution</a>, thermal motion brings them into contact. However, when they are in different phases, the reaction is limited to the interface between the reactants. Reaction can occur only at their area of contact; in the case of a liquid and a gas, at the surface of the liquid. Vigorous shaking and stirring may be needed to bring the reaction to completion. This means that the more finely divided a solid or liquid reactant the greater its <a href="http://en.wikipedia.org/wiki/Surface_area" title="Surface area">surface area</a> per unit <a href="http://en.wikipedia.org/wiki/Volume" title="Volume">volume</a> and the more contact it makes with the other reactant, thus the faster the reaction. To make an analogy, for example, when one starts a fire, one uses wood chips and small branches — one does not start with large logs right away. In organic chemistry, <a href="http://en.wikipedia.org/wiki/On_water_reaction" title="On water reaction">on water reactions</a> are the exception to the rule that homogeneous reactions take place faster than heterogeneous reactions.<br /> <h3> <span class="mw-headline" id="Concentration">Concentration</span></h3> The reactions are due to collisions of reactant species. The frequency with which the molecules or ions collide depends upon their <a href="http://en.wikipedia.org/wiki/Concentration" title="Concentration">concentrations</a>. The more crowded the molecules are, the more likely they are to collide and react with one another. Thus, an increase in the concentrations of the reactants will result in the corresponding increase in the reaction rate, while a decrease in the concentrations will have a reverse effect. For example, <a href="http://en.wikipedia.org/wiki/Combustion" title="Combustion">combustion</a> that occurs in air (21% oxygen) will occur more rapidly in pure oxygen.<br /> <h3> <span class="mw-headline" id="Temperature">Temperature</span></h3> <a href="http://en.wikipedia.org/wiki/Temperature" title="Temperature">Temperature</a> usually has a major effect on the rate of a chemical reaction. Molecules at a higher temperature have more <a href="http://en.wikipedia.org/wiki/Thermal_energy" title="Thermal energy">thermal energy</a>. Although collision frequency is greater at higher temperatures, this alone contributes only a very small proportion to the increase in rate of reaction. Much more important is the fact that the proportion of reactant molecules with sufficient energy to react (energy greater than <a href="http://en.wikipedia.org/wiki/Activation_energy" title="Activation energy">activation energy</a>: <i>E</i> > <i>E</i><sub><i>a</i></sub>) is significantly higher and is explained in detail by the <a href="http://en.wikipedia.org/wiki/Maxwell%E2%80%93Boltzmann_distribution" title="Maxwell–Boltzmann distribution">Maxwell–Boltzmann distribution</a> of molecular energies.<br /> The 'rule of thumb' that the rate of chemical reactions doubles for every 10 °C temperature rise is a common misconception. This may have been generalized from the special case of biological systems, where the <a href="http://en.wikipedia.org/wiki/Q10_%28temperature_coefficient%29" title="Q10 (temperature coefficient)"><i>α</i> (temperature coefficient)</a> is often between 1.5 and 2.5.<br /> A reaction's kinetics can also be studied with a <a href="http://en.wikipedia.org/wiki/Temperature_jump" title="Temperature jump">temperature jump</a> approach. This involves using a sharp rise in temperature and observing the <a class="mw-redirect" href="http://en.wikipedia.org/wiki/Relaxation_time" title="Relaxation time">relaxation time</a> of the return to equilibrium. A particularly useful form of <a href="http://en.wikipedia.org/wiki/Temperature_jump" title="Temperature jump">temperature jump</a> apparatus is a <a href="http://en.wikipedia.org/wiki/Shock_tube" title="Shock tube">shock tube</a>, which can rapidly jump a gas's temperature by more than 1000 degrees.<br /> <h3> <span class="mw-headline" id="Catalysts">Catalysts</span></h3> <div class="thumb tright"> <div class="thumbinner" style="width: 222px;"> <a class="image" href="http://en.wikipedia.org/wiki/File:Activation_energy.svg"><img alt="" class="thumbimage" height="176" src="http://upload.wikimedia.org/wikipedia/commons/thumb/2/24/Activation_energy.svg/220px-Activation_energy.svg.png" width="220" /></a> <div class="thumbcaption"> <div class="magnify"> <a class="internal" href="http://en.wikipedia.org/wiki/File:Activation_energy.svg" title="Enlarge"><img alt="" height="11" src="http://bits.wikimedia.org/static-1.23wmf13/skins/common/images/magnify-clip.png" width="15" /></a></div> Generic potential energy diagram showing the effect of a catalyst in a hypothetical endothermic chemical reaction. The presence of the catalyst opens a different reaction pathway (shown in red) with a lower activation energy. The final result and the overall thermodynamics are the same.</div> </div> </div> A <a class="mw-redirect" href="http://en.wikipedia.org/wiki/Catalyst" title="Catalyst">catalyst</a> is a substance that accelerates the rate of a chemical reaction but remains <a class="mw-redirect" href="http://en.wikipedia.org/wiki/Chemically" title="Chemically">chemically</a> unchanged afterwards. The catalyst increases rate reaction by providing a different <a href="http://en.wikipedia.org/wiki/Reaction_mechanism" title="Reaction mechanism">reaction mechanism</a> to occur with a lower <a href="http://en.wikipedia.org/wiki/Activation_energy" title="Activation energy">activation energy</a>. In <a href="http://en.wikipedia.org/wiki/Autocatalysis" title="Autocatalysis">autocatalysis</a> a reaction product is itself a catalyst for that reaction leading to <a href="http://en.wikipedia.org/wiki/Positive_feedback" title="Positive feedback">positive feedback</a>. Proteins that act as catalysts in biochemical reactions are called <a href="http://en.wikipedia.org/wiki/Enzyme" title="Enzyme">enzymes</a>. <a href="http://en.wikipedia.org/wiki/Michaelis%E2%80%93Menten_kinetics" title="Michaelis–Menten kinetics">Michaelis–Menten kinetics</a> describe the <a href="http://en.wikipedia.org/wiki/Enzyme_kinetics" title="Enzyme kinetics">rate of enzyme mediated reactions</a>. A catalyst does not affect the position of the equilibria, as the catalyst speeds up the backward and forward reactions equally.<br /> In certain organic molecules, specific substituents can have an influence on reaction rate in <a href="http://en.wikipedia.org/wiki/Neighbouring_group_participation" title="Neighbouring group participation">neighbouring group participation</a>.<br /> Agitating or mixing a solution will also accelerate the rate of a chemical reaction, as this gives the particles greater kinetic energy, increasing the number of collisions between reactants and, therefore, the possibility of successful collisions.<br /> <h3> <span class="mw-headline" id="Pressure">Pressure</span></h3> Increasing the pressure in a gaseous reaction will increase the number of collisions between reactants, increasing the rate of reaction. This is because the <a class="mw-redirect" href="http://en.wikipedia.org/wiki/Activity_%28chemistry%29" title="Activity (chemistry)">activity</a> of a gas is directly proportional to the partial pressure of the gas. This is similar to the effect of increasing the concentration of a solution.<br /> In addition to this straightforward mass-action effect, the rate coefficients themselves can change due to pressure. The rate coefficients and products of many high-temperature gas-phase reactions change if an inert gas is added to the mixture; variations on this effect are called <a class="new" href="http://en.wikipedia.org/w/index.php?title=Fall-off&action=edit&redlink=1" title="Fall-off (page does not exist)">fall-off</a> and <a class="new" href="http://en.wikipedia.org/w/index.php?title=Chemical_activation&action=edit&redlink=1" title="Chemical activation (page does not exist)">chemical activation</a>. These phenomena are due to exothermic or endothermic reactions occurring faster than heat transfer, causing the reacting molecules to have non-thermal energy distributions (non-<a href="http://en.wikipedia.org/wiki/Boltzmann_distribution" title="Boltzmann distribution">Boltzmann distribution</a>). Increasing the pressure increases the heat transfer rate between the reacting molecules and the rest of the system, reducing this effect.<br /> Condensed-phase rate coefficients can also be affected by (very high) pressure; this is a completely different effect than fall-off or chemical-activation. It is often studied using <a class="mw-redirect" href="http://en.wikipedia.org/wiki/Diamond_anvil" title="Diamond anvil">diamond anvils</a>.<br /> A reaction's kinetics can also be studied with a <a href="http://en.wikipedia.org/wiki/Pressure_jump" title="Pressure jump">pressure jump</a> approach. This involves making fast changes in pressure and observing the <a class="mw-redirect" href="http://en.wikipedia.org/wiki/Relaxation_time" title="Relaxation time">relaxation time</a> of the return to equilibrium.<br /> <h2> <span class="mw-headline" id="Equilibrium">Equilibrium</span></h2> While a chemical kinetics is concerned with the rate of a chemical reaction, <a href="http://en.wikipedia.org/wiki/Thermodynamics" title="Thermodynamics">thermodynamics</a> determines the extent to which reactions occur. In a <a href="http://en.wikipedia.org/wiki/Reversible_reaction" title="Reversible reaction">reversible reaction</a>, chemical equilibrium is reached when the rates of the forward and reverse reactions are equal (the principle of <a href="http://en.wikipedia.org/wiki/Detailed_balance" title="Detailed balance">detailed balance</a>) and the concentrations of the <a class="mw-redirect" href="http://en.wikipedia.org/wiki/Reactant" title="Reactant">reactants</a> and <a href="http://en.wikipedia.org/wiki/Product_%28chemistry%29" title="Product (chemistry)">products</a> no longer change. This is demonstrated by, for example, the <a class="mw-redirect" href="http://en.wikipedia.org/wiki/Haber%E2%80%93Bosch_process" title="Haber–Bosch process">Haber–Bosch process</a> for combining nitrogen and hydrogen to produce ammonia. <a href="http://en.wikipedia.org/wiki/Chemical_clock" title="Chemical clock">Chemical clock</a> reactions such as the <a href="http://en.wikipedia.org/wiki/Belousov%E2%80%93Zhabotinsky_reaction" title="Belousov–Zhabotinsky reaction">Belousov–Zhabotinsky reaction</a> demonstrate that component concentrations can oscillate for a long time before finally attaining the equilibrium.<br /> <h2> <span class="mw-headline" id="Free_energy">Free energy</span></h2> In general terms, the <a href="http://en.wikipedia.org/wiki/Thermodynamic_free_energy" title="Thermodynamic free energy">free energy change (ΔG)</a> of a reaction determines whether a chemical change will take place, but kinetics describes how fast the reaction is. A reaction can be very <a href="http://en.wikipedia.org/wiki/Exothermic" title="Exothermic">exothermic</a> and have a very positive <a href="http://en.wikipedia.org/wiki/Entropy" title="Entropy">entropy</a> change but will not happen in practice if the reaction is too slow. If a reactant can produce two different products, the thermodynamically most stable one will in general form, except in special circumstances when the reaction is said to be under <a class="mw-redirect" href="http://en.wikipedia.org/wiki/Kinetic_reaction_control" title="Kinetic reaction control">kinetic reaction control</a>. The <a href="http://en.wikipedia.org/wiki/Curtin%E2%80%93Hammett_principle" title="Curtin–Hammett principle">Curtin–Hammett principle</a> applies when determining the product ratio for two reactants interconverting rapidly, each going to a different product. It is possible to make predictions about reaction rate constants for a reaction from <a href="http://en.wikipedia.org/wiki/Free-energy_relationship" title="Free-energy relationship">free-energy relationships</a>.<br /> The <a href="http://en.wikipedia.org/wiki/Kinetic_isotope_effect" title="Kinetic isotope effect">kinetic isotope effect</a> is the difference in the rate of a chemical reaction when an atom in one of the reactants is replaced by one of its <a href="http://en.wikipedia.org/wiki/Isotope" title="Isotope">isotopes</a>.<br /> Chemical kinetics provides information on <a href="http://en.wikipedia.org/wiki/Residence_time" title="Residence time">residence time</a> and <a href="http://en.wikipedia.org/wiki/Heat_transfer" title="Heat transfer">heat transfer</a> in a <a href="http://en.wikipedia.org/wiki/Chemical_reactor" title="Chemical reactor">chemical reactor</a> in <a href="http://en.wikipedia.org/wiki/Chemical_engineering" title="Chemical engineering">chemical engineering</a> and the <a href="http://en.wikipedia.org/wiki/Molar_mass_distribution" title="Molar mass distribution">molar mass distribution</a> in <a href="http://en.wikipedia.org/wiki/Polymer_chemistry" title="Polymer chemistry">polymer chemistry</a>.<br /> <h2> <span class="mw-headline" id="Applications">Applications</span></h2> The mathematical models that describe chemical reaction kinetics provide chemists and chemical engineers with tools to better understand and describe chemical processes such as food decomposition, microorganism growth, stratospheric ozone decomposition, and the complex chemistry of biological systems. These models can also be used in the design or modification of chemical reactors to optimize product yield, more efficiently separate products, and eliminate environmentally harmful by-products. When performing <a class="mw-redirect" href="http://en.wikipedia.org/wiki/Catalytic_cracking" title="Catalytic cracking">catalytic cracking</a> of heavy hydrocarbons into gasoline and light gas, for example, kinetic models can be used to find the temperature and pressure at which the highest yield of heavy hydrocarbons into gasoline will occur. Kinetics is also a basic aspect of chemistry.<br /> <h2> <span class="mw-headline" id="See_also">See also</span></h2> <ul> <li><a class="mw-redirect" href="http://en.wikipedia.org/wiki/Autocatalytic_reactions_and_order_creation" title="Autocatalytic reactions and order creation">Autocatalytic reactions and order creation</a></li> <li><a href="http://en.wikipedia.org/wiki/Detonation" title="Detonation">Detonation</a></li> <li><a href="http://en.wikipedia.org/wiki/Enthalpy" title="Enthalpy">Enthalpy</a></li> <li><a href="http://en.wikipedia.org/wiki/Flame_speed" title="Flame speed">Flame speed</a></li> <li><a href="http://en.wikipedia.org/wiki/Nonthermal_surface_reaction" title="Nonthermal surface reaction">Nonthermal surface reaction</a></li> <li><a href="http://en.wikipedia.org/wiki/PottersWheel" title="PottersWheel">PottersWheel</a> Matlab toolbox to fit chemical rate constants to experimental data</li> <li><a href="http://en.wikipedia.org/wiki/Reaction_progress_kinetic_analysis" title="Reaction progress kinetic analysis">Reaction progress kinetic analysis</a></li> <li><a href="http://en.wikipedia.org/wiki/Two-dimensional_gas" title="Two-dimensional gas">Two-dimensional gas</a></li> </ul> <h2> <span class="mw-headline" id="References">References</span></h2> <ul> <li><i>Preparing for the Chemistry AP Exam</i>. Upper Saddle River, New Jersey: Pearson Education, 2004. 131–134. <a class="internal mw-magiclink-isbn" href="http://en.wikipedia.org/wiki/Special:BookSources/0536731578">ISBN 0-536-73157-8</a></li> </ul> </div> http://scholarpharma.blogspot.com/2014/02/chemical-kinetics.html1margipatel02@gmail.com (margipatel02@gmail.com)tag:blogger.com,1999:blog-8563020669307343167.post-5609239476363175105Fri, 21 Feb 2014 10:00:00 +00002014-02-21T02:00:27.389-08:00Electron pair <div dir="ltr" style="text-align: left;" trbidi="on"> <h1 class="firstHeading" id="firstHeading" lang="en" style="text-align: center;"> <span style="color: #0b5394;"><span dir="auto">Electron pair</span></span></h1> <h1 class="firstHeading" id="firstHeading" lang="en" style="text-align: center;"> <span dir="auto"><span style="color: purple;"><span style="font-size: small;">                                                                             By Miss Sejal D Jethva</span></span></span></h1> <br />In <a href="http://en.wikipedia.org/wiki/Chemistry" title="Chemistry">chemistry</a>, an <b>electron pair</b> or a <b>Lewis pair</b> consists of two electrons that occupy the same <a href="http://en.wikipedia.org/wiki/Molecular_orbital" title="Molecular orbital">orbital</a> but have opposite <a href="http://en.wikipedia.org/wiki/Spin_%28physics%29" title="Spin (physics)">spins</a>. The electron pair concept was introduced in a 1916 paper of <a href="http://en.wikipedia.org/wiki/Gilbert_N._Lewis" title="Gilbert N. Lewis">Gilbert N. Lewis</a>.<sup class="reference" id="cite_ref-1"><a href="http://en.wikipedia.org/wiki/Electron_pair#cite_note-1"><span>[</span>1<span>]</span></a></sup><br /> <div class="thumb tright"> <div class="thumbinner" style="width: 202px;"> <a class="image" href="http://en.wikipedia.org/wiki/File:Covalent%26PolarBond.png"><img alt="" class="thumbimage" height="106" src="http://upload.wikimedia.org/wikipedia/commons/thumb/a/af/Covalent%26PolarBond.png/200px-Covalent%26PolarBond.png" width="200" /></a> <div class="thumbcaption"> <div class="magnify"> <a class="internal" href="http://en.wikipedia.org/wiki/File:Covalent%26PolarBond.png" title="Enlarge"><img alt="" height="11" src="http://bits.wikimedia.org/static-1.23wmf13/skins/common/images/magnify-clip.png" width="15" /></a></div> <a class="mw-redirect" href="http://en.wikipedia.org/wiki/MO_diagram" title="MO diagram">MO diagrams</a> depicting covalent (left) and polar covalent (right) bonding in a <a href="http://en.wikipedia.org/wiki/Diatomic_molecule" title="Diatomic molecule">diatomic molecule</a>. In both cases a bond is created by the formation of an electron pair.</div> </div> </div> Because electrons are <a href="http://en.wikipedia.org/wiki/Fermion" title="Fermion">fermions</a>, the <a href="http://en.wikipedia.org/wiki/Pauli_exclusion_principle" title="Pauli exclusion principle">Pauli exclusion principle</a> forbids these particles from having exactly the same <a class="mw-redirect" href="http://en.wikipedia.org/wiki/Quantum_numbers" title="Quantum numbers">quantum numbers</a>. Therefore the only way to occupy the same orbital, i.e. have the same <a class="mw-redirect" href="http://en.wikipedia.org/wiki/Orbital_quantum_number" title="Orbital quantum number">orbital quantum numbers</a>, is to differ in the <a href="http://en.wikipedia.org/wiki/Spin_quantum_number" title="Spin quantum number">spin quantum number</a>. This limits the number of electrons in the same orbital to exactly two.<br /> The pairing of spins is often energetically favorable and electron pairs therefore play a very large role in <a href="http://en.wikipedia.org/wiki/Chemistry" title="Chemistry">chemistry</a>. They can form<br /> <ol> <li>a <a href="http://en.wikipedia.org/wiki/Chemical_bond" title="Chemical bond">chemical bond</a> between two atoms</li> <li>as a <a href="http://en.wikipedia.org/wiki/Lone_pair" title="Lone pair">lone pair</a>.</li> <li>fill the <a href="http://en.wikipedia.org/wiki/Core_electron" title="Core electron">core levels</a> of an atom.</li> </ol> Because the spins are paired, the magnetic moment of the electrons cancels and the contribution of the pair to the magnetic properties will in general be a <a href="http://en.wikipedia.org/wiki/Diamagnetism" title="Diamagnetism">diamagnetic one</a>.<br /> Although a strong tendency to pair off electrons can be observed in chemistry, it is also possible that electrons occur as <a href="http://en.wikipedia.org/wiki/Unpaired_electron" title="Unpaired electron">unpaired electrons</a>.<br /> In the case of <a href="http://en.wikipedia.org/wiki/Metallic_bonding" title="Metallic bonding">metallic bonding</a> the magnetic moments also compensate to a large extent, but the bonding is more communal so that individual pairs of electrons cannot be distinguished and it is better to consider the electrons as a collective 'ocean'.<br /> A very special case of electron pair formation occurs in <a href="http://en.wikipedia.org/wiki/Superconductivity" title="Superconductivity">superconductivity</a>: the formation of <a href="http://en.wikipedia.org/wiki/Cooper_pair" title="Cooper pair">Cooper pairs</a>.</div> http://scholarpharma.blogspot.com/2014/02/electron-pair.html1margipatel02@gmail.com (margipatel02@gmail.com)tag:blogger.com,1999:blog-8563020669307343167.post-6645256134925155245Fri, 21 Feb 2014 09:55:00 +00002014-02-21T01:55:21.729-08:00Alkylating antineoplastic agent By Dr.Rajarshi N Patel & Mr.Dharam M Pandya<div dir="ltr" style="text-align: left;" trbidi="on"> <h1 class="firstHeading" id="firstHeading" lang="en" style="text-align: center;"> <span style="color: red;"><span dir="auto">Alkylating antineoplastic agent</span></span></h1> <h1 class="firstHeading" id="firstHeading" lang="en"> <span style="color: red;"><span dir="auto">                                       <span style="color: blue;">  <span style="font-size: small;">Dr.Rajarshi N Patel & Mr.Dharam M Pandya</span></span></span></span></h1> <div id="siteSub"> </div> An <b>alkylating antineoplastic agent</b> is an <a class="mw-redirect" href="http://en.wikipedia.org/wiki/Alkylating_agent" title="Alkylating agent">alkylating agent</a> used in cancer treatment that attaches an <a href="http://en.wikipedia.org/wiki/Alkyl" title="Alkyl">alkyl</a> group (C<sub>n</sub>H<sub>2n+1</sub>) to <a href="http://en.wikipedia.org/wiki/DNA" title="DNA">DNA</a>.<sup class="reference" id="cite_ref-urlantineop_1-0"><a href="http://en.wikipedia.org/wiki/Alkylating_antineoplastic_agent#cite_note-urlantineop-1"><span>[</span>1<span>]</span></a></sup><br /> The alkyl group is attached to the <a href="http://en.wikipedia.org/wiki/Guanine" title="Guanine">guanine</a> base of DNA, at the number 7 nitrogen atom of the <a href="http://en.wikipedia.org/wiki/Purine" title="Purine">purine</a> ring.<br /> Since <a href="http://en.wikipedia.org/wiki/Cancer" title="Cancer">cancer</a> cells, in general, proliferate faster and with less error-correcting than healthy cells, cancer cells are more sensitive to DNA damage — such as being alkylated. Alkylating agents are used to treat several cancers. However, they are also toxic to normal cells (<a class="mw-redirect" href="http://en.wikipedia.org/wiki/Cytotoxic" title="Cytotoxic">cytotoxic</a>), leading to damage, in particular in <a href="http://en.wikipedia.org/wiki/Labile_cell" title="Labile cell">cells that divide frequently</a>, as those in the gastrointestinal tract, bone marrow, testicles and ovaries, which can cause loss of fertility. Most of the alkylating agents are also <a class="mw-redirect" href="http://en.wikipedia.org/wiki/Carcinogenic" title="Carcinogenic">carcinogenic</a>. Hyperthermia is especially effective at enhancing the effects of alkylating agents.<sup class="reference" id="cite_ref-pmid9081372_2-0"><a href="http://en.wikipedia.org/wiki/Alkylating_antineoplastic_agent#cite_note-pmid9081372-2"><span>[</span>2<span>]</span></a></sup><br /> <div class="toc" id="toc"> <div id="toctitle"> <h2> Contents</h2> </div> <ul> <li class="toclevel-1 tocsection-1"><a href="http://en.wikipedia.org/wiki/Alkylating_antineoplastic_agent#History"><span class="tocnumber">1</span> <span class="toctext">History</span></a></li> <li class="toclevel-1 tocsection-2"><a href="http://en.wikipedia.org/wiki/Alkylating_antineoplastic_agent#Agents_acting_nonspecifically"><span class="tocnumber">2</span> <span class="toctext">Agents acting nonspecifically</span></a></li> <li class="toclevel-1 tocsection-3"><a href="http://en.wikipedia.org/wiki/Alkylating_antineoplastic_agent#Agents_requiring_activation"><span class="tocnumber">3</span> <span class="toctext">Agents requiring activation</span></a></li> <li class="toclevel-1 tocsection-4"><a href="http://en.wikipedia.org/wiki/Alkylating_antineoplastic_agent#Dialkylating_agents.2C_limpet_attachment.2C_and_monoalkylating_agents"><span class="tocnumber">4</span> <span class="toctext">Dialkylating agents, limpet attachment, and monoalkylating agents</span></a></li> <li class="toclevel-1 tocsection-5"><a href="http://en.wikipedia.org/wiki/Alkylating_antineoplastic_agent#Examples"><span class="tocnumber">5</span> <span class="toctext">Examples</span></a> <ul> <li class="toclevel-2 tocsection-6"><a href="http://en.wikipedia.org/wiki/Alkylating_antineoplastic_agent#Classical_alkylating_agents"><span class="tocnumber">5.1</span> <span class="toctext">Classical alkylating agents</span></a></li> <li class="toclevel-2 tocsection-7"><a href="http://en.wikipedia.org/wiki/Alkylating_antineoplastic_agent#Alkylating-like"><span class="tocnumber">5.2</span> <span class="toctext">Alkylating-like</span></a></li> <li class="toclevel-2 tocsection-8"><a href="http://en.wikipedia.org/wiki/Alkylating_antineoplastic_agent#Nonclassical"><span class="tocnumber">5.3</span> <span class="toctext">Nonclassical</span></a></li> </ul> </li> <li class="toclevel-1 tocsection-9"><a href="http://en.wikipedia.org/wiki/Alkylating_antineoplastic_agent#Limitations"><span class="tocnumber">6</span> <span class="toctext">Limitations</span></a></li> <li class="toclevel-1 tocsection-10"><a href="http://en.wikipedia.org/wiki/Alkylating_antineoplastic_agent#References"><span class="tocnumber">7</span> <span class="toctext">References</span></a></li> <li class="toclevel-1 tocsection-11"><a href="http://en.wikipedia.org/wiki/Alkylating_antineoplastic_agent#External_links"><span class="tocnumber">8</span> <span class="toctext">External links</span></a></li> </ul> </div> <h2> <span class="mw-headline" id="History">History</span></h2> Before their use in chemotherapy, alkylating agents were better known for their use as <a href="http://en.wikipedia.org/wiki/Sulfur_mustard" title="Sulfur mustard">sulfur mustard</a>, ("mustard gas") and related <a href="http://en.wikipedia.org/wiki/Chemical_weapon" title="Chemical weapon">chemical weapons</a> in <a href="http://en.wikipedia.org/wiki/World_War_I" title="World War I">World War I</a>. The <a class="mw-redirect" href="http://en.wikipedia.org/wiki/Nitrogen_mustards" title="Nitrogen mustards">nitrogen mustards</a> were the first alkylating agents used medically, as well as the first modern cancer chemotherapies. Goodman, Gilman, and others at Yale began studying nitrogen mustards at Yale in 1942, and, following the sometimes dramatic but highly variable responses of experimental tumors in mice to treatment, these agents were first tested in humans late that year. Use of methyl bis (B-chloroethyl)emine hydrochloride (<a class="mw-redirect" href="http://en.wikipedia.org/wiki/Mechlorethamine" title="Mechlorethamine">mechlorethamine</a>, mustine) and tris (B-chloroethy) amine hydrochloride for Hodgkin's disease lymphosarcoma, leukemia, and other malignancies resulted in striking but temporary dissolution of tumor masses. Because of secrecy surrounding the war gas program, these results were not published until 1946.<sup class="reference" id="cite_ref-3"><a href="http://en.wikipedia.org/wiki/Alkylating_antineoplastic_agent#cite_note-3"><span>[</span>3<span>]</span></a></sup> These publications spurred rapid advancement in the previously non-existent field of cancer chemotherapy, and a wealth of new alkylating agents with therapeutic effect were discovered over the following two decades.<sup class="reference" id="cite_ref-Scott_4-0"><a href="http://en.wikipedia.org/wiki/Alkylating_antineoplastic_agent#cite_note-Scott-4"><span>[</span>4<span>]</span></a></sup><br /> A common myth holds that Goodman and Gilman were prompted to study nitrogen mustards as a potential treatment for cancer following a 1943 incident in <a class="mw-redirect" href="http://en.wikipedia.org/wiki/Bari,_Italy" title="Bari, Italy">Bari, Italy</a>, where survivors exposed to mustard gas became <a href="http://en.wikipedia.org/wiki/Leukopenia" title="Leukopenia">leukopenic</a>. In fact, animal and human trials had begun the previous year, Gilman makes no mention of such an episode in his recounting of the early trials of nitrogen mustards,<sup class="reference" id="cite_ref-5"><a href="http://en.wikipedia.org/wiki/Alkylating_antineoplastic_agent#cite_note-5"><span>[</span>5<span>]</span></a></sup> and the marrow suppressing effects of mustard gas had been known since the close of World War I.<sup class="reference" id="cite_ref-Scott_4-1"><a href="http://en.wikipedia.org/wiki/Alkylating_antineoplastic_agent#cite_note-Scott-4"><span>[</span>4<span>]</span></a></sup><br /> <h2> <span class="mw-headline" id="Agents_acting_nonspecifically">Agents acting nonspecifically</span></h2> Some alkylating agents are active under conditions present in cells; and the same mechanism that makes them toxic allows them to be used as anti-cancer drugs. They stop tumor growth by crosslinking <a href="http://en.wikipedia.org/wiki/Guanine" title="Guanine">guanine</a> <a href="http://en.wikipedia.org/wiki/Nucleobase" title="Nucleobase">nucleobases</a> in <a href="http://en.wikipedia.org/wiki/DNA" title="DNA">DNA</a> double-helix strands, directly attacking DNA. This makes the strands unable to uncoil and separate. As this is necessary in DNA replication, the cells can no longer divide. These drugs act nonspecifically.<br /> <h2> <span class="mw-headline" id="Agents_requiring_activation">Agents requiring activation</span></h2> Some of the substances require conversion into active substances <i>in vivo</i> (e.g., <a href="http://en.wikipedia.org/wiki/Cyclophosphamide" title="Cyclophosphamide">cyclophosphamide</a>).<br /> <a href="http://en.wikipedia.org/wiki/Cyclophosphamide" title="Cyclophosphamide">Cyclophosphamide</a> is one of the most potent immunosuppressive substances. In small dosages, it is very efficient in the therapy of systemic lupus erythematosus, autoimmune <a href="http://en.wikipedia.org/wiki/Hemolysis#Hemolytic_anemia" title="Hemolysis">hemolytic anemias</a>, <a class="mw-redirect" href="http://en.wikipedia.org/wiki/Wegener%27s_granulomatosis" title="Wegener's granulomatosis">Wegener's granulomatosis</a>, and other <a href="http://en.wikipedia.org/wiki/Autoimmune_disease" title="Autoimmune disease">autoimmune diseases</a>. High dosages cause <a href="http://en.wikipedia.org/wiki/Pancytopenia" title="Pancytopenia">pancytopenia</a> and hemorrhagic <a class="mw-redirect" href="http://en.wikipedia.org/wiki/Cystitis" title="Cystitis">cystitis</a>.<br /> <h2> <span class="mw-headline" id="Dialkylating_agents.2C_limpet_attachment.2C_and_monoalkylating_agents">Dialkylating agents, limpet attachment, and monoalkylating agents</span></h2> <i>Dialkylating agents</i> can react with two different 7-N-guanine residues, and, if these are in different strands of DNA, the result is <a href="http://en.wikipedia.org/wiki/Cross-link" title="Cross-link">cross-linkage</a> of the DNA strands, which prevents uncoiling of the DNA double helix. If the two guanine residues are in the same strand, the result is called <i>limpet attachment</i> of the drug molecule to the DNA. <a href="http://en.wikipedia.org/wiki/Busulfan" title="Busulfan">Busulfan</a> is an example of a dialkylating agent: it is the <a class="mw-redirect" href="http://en.wikipedia.org/wiki/Methanesulfonate" title="Methanesulfonate">methanesulfonate</a> <a class="mw-redirect" href="http://en.wikipedia.org/wiki/Diester" title="Diester">diester</a> of <a class="mw-redirect" href="http://en.wikipedia.org/wiki/1,4-butanediol" title="1,4-butanediol">1,4-butanediol</a>. Methanesulfonate can be eliminated as a <a href="http://en.wikipedia.org/wiki/Leaving_group" title="Leaving group">leaving group</a>. Both ends of the molecule can be attacked by DNA bases, producing a butylene crosslink between two different bases.<br /> <i>Monoalkylating agents</i> can react only with one 7-N of guanine.<br /> Limpet attachment and monoalkylation do not prevent the separation of the two DNA strands of the double helix but do prevent vital DNA-processing <a href="http://en.wikipedia.org/wiki/Enzyme" title="Enzyme">enzymes</a> from accessing the DNA. The final result is inhibition of cell growth or stimulation of <a href="http://en.wikipedia.org/wiki/Apoptosis" title="Apoptosis">apoptosis</a>, cell suicide.<br /> <h2> <span class="mw-headline" id="Examples">Examples</span></h2> In the <a href="http://en.wikipedia.org/wiki/Anatomical_Therapeutic_Chemical_Classification_System" title="Anatomical Therapeutic Chemical Classification System">Anatomical Therapeutic Chemical Classification System</a>, alkylating agents are classified under <a href="http://en.wikipedia.org/wiki/ATC_code_L01#L01A_Alkylating_agents" title="ATC code L01">L01A</a>.<br /> <h3> <span class="mw-headline" id="Classical_alkylating_agents">Classical alkylating agents</span></h3> Many of the agents are known as "Classical alkylating agents". These include true <a href="http://en.wikipedia.org/wiki/Alkyl" title="Alkyl">alkyl</a> groups, and have been known for a longer time than some of the other alkylating agents. Examples include <a href="http://en.wikipedia.org/wiki/Melphalan" title="Melphalan">melphalan</a> and <a href="http://en.wikipedia.org/wiki/Chlorambucil" title="Chlorambucil">chlorambucil</a>.<sup class="reference" id="cite_ref-pmid10500495_6-0"><a href="http://en.wikipedia.org/wiki/Alkylating_antineoplastic_agent#cite_note-pmid10500495-6"><span>[</span>6<span>]</span></a></sup><br /> They destroy proliferating cancer cells by adding an alkyl group to DNA molecule and preventing its replication.<br /> The following three groups are almost always considered "classical".<br /> <ul> <li><a href="http://en.wikipedia.org/wiki/Nitrogen_mustard" title="Nitrogen mustard">Nitrogen mustards</a><sup class="reference" id="cite_ref-takimoto_7-0"><a href="http://en.wikipedia.org/wiki/Alkylating_antineoplastic_agent#cite_note-takimoto-7"><span>[</span>7<span>]</span></a></sup> <ul> <li><a href="http://en.wikipedia.org/wiki/Cyclophosphamide" title="Cyclophosphamide">Cyclophosphamide</a></li> <li><a class="mw-redirect" href="http://en.wikipedia.org/wiki/Mechlorethamine" title="Mechlorethamine">Mechlorethamine</a> or <b>mustine (HN2)</b> (trade name <a class="mw-redirect" href="http://en.wikipedia.org/wiki/Mustargen" title="Mustargen">Mustargen</a>)</li> <li><a href="http://en.wikipedia.org/wiki/Uramustine" title="Uramustine">Uramustine</a> or <b>uracil mustard</b></li> <li><a href="http://en.wikipedia.org/wiki/Melphalan" title="Melphalan">Melphalan</a></li> <li><a href="http://en.wikipedia.org/wiki/Chlorambucil" title="Chlorambucil">Chlorambucil</a></li> <li><a href="http://en.wikipedia.org/wiki/Ifosfamide" title="Ifosfamide">Ifosfamide</a></li> <li><a href="http://en.wikipedia.org/wiki/Bendamustine" title="Bendamustine">Bendamustine</a></li> </ul> </li> </ul> <ul> <li><a href="http://en.wikipedia.org/wiki/Nitrosourea" title="Nitrosourea">Nitrosoureas</a> <ul> <li><a href="http://en.wikipedia.org/wiki/Carmustine" title="Carmustine">Carmustine</a></li> <li><a href="http://en.wikipedia.org/wiki/Lomustine" title="Lomustine">Lomustine</a></li> <li><a class="mw-redirect" href="http://en.wikipedia.org/wiki/Streptozocin" title="Streptozocin">Streptozocin</a></li> </ul> </li> </ul> <ul> <li><a class="mw-redirect" href="http://en.wikipedia.org/wiki/Alkyl_sulfonates" title="Alkyl sulfonates">Alkyl sulfonates</a> <ul> <li><a href="http://en.wikipedia.org/wiki/Busulfan" title="Busulfan">Busulfan</a></li> </ul> </li> </ul> <a class="mw-redirect" href="http://en.wikipedia.org/wiki/Thiotepa" title="Thiotepa">Thiotepa</a> and its analogues are usually considered classical, but can be considered nonclassical.<br /> <h3> <span class="mw-headline" id="Alkylating-like">Alkylating-like</span></h3> <a class="mw-redirect" href="http://en.wikipedia.org/wiki/Platinum-based_chemotherapeutic_drug" title="Platinum-based chemotherapeutic drug">Platinum-based chemotherapeutic drugs</a> (termed platinum analogues) act in a similar manner. These agents do not have an <a href="http://en.wikipedia.org/wiki/Alkyl" title="Alkyl">alkyl</a> group, but nevertheless damage DNA.<sup class="reference" id="cite_ref-pmid18289945_8-0"><a href="http://en.wikipedia.org/wiki/Alkylating_antineoplastic_agent#cite_note-pmid18289945-8"><span>[</span>8<span>]</span></a></sup> They permanently coordinate to DNA to interfere with DNA repair, so they are sometimes described as "alkylating-like".<br /> <ul> <li>Platinum<sup class="reference" id="cite_ref-takimoto_7-1"><a href="http://en.wikipedia.org/wiki/Alkylating_antineoplastic_agent#cite_note-takimoto-7"><span>[</span>7<span>]</span></a></sup> <ul> <li><a href="http://en.wikipedia.org/wiki/Cisplatin" title="Cisplatin">Cisplatin</a></li> <li><a href="http://en.wikipedia.org/wiki/Carboplatin" title="Carboplatin">Carboplatin</a></li> <li><a href="http://en.wikipedia.org/wiki/Nedaplatin" title="Nedaplatin">Nedaplatin</a></li> <li><a href="http://en.wikipedia.org/wiki/Oxaliplatin" title="Oxaliplatin">Oxaliplatin</a></li> <li><a href="http://en.wikipedia.org/wiki/Satraplatin" title="Satraplatin">Satraplatin</a></li> <li><a href="http://en.wikipedia.org/wiki/Triplatin_tetranitrate" title="Triplatin tetranitrate">Triplatin tetranitrate</a></li> </ul> </li> </ul> These agents also bind at N7 of guanine.<br /> <h3> <span class="mw-headline" id="Nonclassical">Nonclassical</span></h3> Certain alkylating agents are sometimes described as "nonclassical". There is not a perfect consensus on which items are included in this category, but, in general, they include:<br /> <ul> <li><a href="http://en.wikipedia.org/wiki/Procarbazine" title="Procarbazine">procarbazine</a><sup class="reference" id="cite_ref-pmid18360630_9-0"><a href="http://en.wikipedia.org/wiki/Alkylating_antineoplastic_agent#cite_note-pmid18360630-9"><span>[</span>9<span>]</span></a></sup></li> </ul> <ul> <li><a href="http://en.wikipedia.org/wiki/Altretamine" title="Altretamine">altretamine</a><sup class="reference" id="cite_ref-isbn0-443-06527-6_10-0"><a href="http://en.wikipedia.org/wiki/Alkylating_antineoplastic_agent#cite_note-isbn0-443-06527-6-10"><span>[</span>10<span>]</span></a></sup></li> </ul> <ul> <li>Some sources explicitly exclude the <a href="http://en.wikipedia.org/wiki/Tetrazine" title="Tetrazine">tetrazines</a> (<a href="http://en.wikipedia.org/wiki/Dacarbazine" title="Dacarbazine">dacarbazine</a>, <a href="http://en.wikipedia.org/wiki/Mitozolomide" title="Mitozolomide">mitozolomide</a>, <a href="http://en.wikipedia.org/wiki/Temozolomide" title="Temozolomide">temozolomide</a>) from the nonclassical category.<sup class="reference" id="cite_ref-isbn3-540-66508-0_11-0"><a href="http://en.wikipedia.org/wiki/Alkylating_antineoplastic_agent#cite_note-isbn3-540-66508-0-11"><span>[</span>11<span>]</span></a></sup> However, other sources list <a href="http://en.wikipedia.org/wiki/Dacarbazine" title="Dacarbazine">dacarbazine</a> as nonclassical,<sup class="reference" id="cite_ref-isbn0-632-03998-1_12-0"><a href="http://en.wikipedia.org/wiki/Alkylating_antineoplastic_agent#cite_note-isbn0-632-03998-1-12"><span>[</span>12<span>]</span></a></sup> and some include <a href="http://en.wikipedia.org/wiki/Temozolomide" title="Temozolomide">temozolomide</a>.<sup class="reference" id="cite_ref-isbn0-07-147781-0_13-0"><a href="http://en.wikipedia.org/wiki/Alkylating_antineoplastic_agent#cite_note-isbn0-07-147781-0-13"><span>[</span>13<span>]</span></a></sup></li> </ul> <ul> <li>The platinum agents are also sometimes described as nonclassical.<sup class="reference" id="cite_ref-isbn0-7817-5492-5_14-0"><a href="http://en.wikipedia.org/wiki/Alkylating_antineoplastic_agent#cite_note-isbn0-7817-5492-5-14"><span>[</span>14<span>]</span></a></sup></li> </ul> <h2> <span class="mw-headline" id="Limitations">Limitations</span></h2> Alkylating antineoplastic agents have limitations. Their functionality has been found to be limited when in the presence of the DNA-repair enzyme <a href="http://en.wikipedia.org/wiki/O-6-methylguanine-DNA_methyltransferase" title="O-6-methylguanine-DNA methyltransferase">O-6-methylguanine-DNA methyltransferase</a> (MGMT). Cross-linking of double-stranded DNA by alkylating agents is inhibited by the cellular DNA-repair mechanism, MGMT. If the MGMT promoter region is methylated, the cells no longer produce MGMT, and are therefore more responsive to alkylating agents. Methylation of the MGMT promoter in gliomas is a useful predictor of the responsiveness of tumors to alkylating agents.<sup class="reference" id="cite_ref-15"><a href="http://en.wikipedia.org/wiki/Alkylating_antineoplastic_agent#cite_note-15"><span>[</span>15<span>]</span></a></sup><br /> <br /> <h2> <span class="mw-headline" id="References">References</span></h2> <div class="reflist columns references-column-count references-column-count-2" style="-moz-column-count: 2; -webkit-column-count: 2; column-count: 2; list-style-type: decimal;"> <ol class="references"> <li id="cite_note-urlantineop-1"><span class="mw-cite-backlink"><b><a href="http://en.wikipedia.org/wiki/Alkylating_antineoplastic_agent#cite_ref-urlantineop_1-0"><span class="cite-accessibility-label">Jump up </span>^</a></b></span> <span class="reference-text"><span class="citation web"><a class="external text" href="http://faculty.swosu.edu/scott.long/phcl/antineop.htm" rel="nofollow">"antineop"</a>. <a class="external text" href="http://web.archive.org/web/20090307052941/http://faculty.swosu.edu/scott.long/phcl/antineop.htm" rel="nofollow">Archived</a> from the original on 7 March 2009<span class="reference-accessdate">. Retrieved 2009-01-24</span>.</span><span class="Z3988" title="ctx_ver=Z39.88-2004&rfr_id=info%3Asid%2Fen.wikipedia.org%3AAlkylating+antineoplastic+agent&rft.btitle=antineop&rft.genre=book&rft_id=http%3A%2F%2Ffaculty.swosu.edu%2Fscott.long%2Fphcl%2Fantineop.htm&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook"></span></span></li> <li id="cite_note-pmid9081372-2"><span class="mw-cite-backlink"><b><a href="http://en.wikipedia.org/wiki/Alkylating_antineoplastic_agent#cite_ref-pmid9081372_2-0"><span class="cite-accessibility-label">Jump up </span>^</a></b></span> <span class="reference-text"><span class="citation journal">Wiedemann GJ, Robins HI, Gutsche S, Mentzel M, Deeken M, Katschinski DM, Eleftheriadis S, Crahé R, Weiss C, Storer B, Wagner T. (May 1996). <a class="external text" href="http://cancerres.aacrjournals.org/cgi/reprint/54/20/5346.pdf" rel="nofollow">"Ifosfamide, carboplatin and etoposide (ICE) combined with 41.8 degrees C whole body hyperthermia in patients with refractory sarcoma"</a>. <i><a href="http://en.wikipedia.org/wiki/European_Journal_of_Cancer" title="European Journal of Cancer">European Journal of Cancer</a></i> <b>32A</b> (5): 888–92. <a class="mw-redirect" href="http://en.wikipedia.org/wiki/PubMed_Identifier" title="PubMed Identifier">PMID</a> <a class="external text" href="http://www.ncbi.nlm.nih.gov/pubmed/9081372" rel="nofollow">9081372</a>.</span><span class="Z3988" title="ctx_ver=Z39.88-2004&rfr_id=info%3Asid%2Fen.wikipedia.org%3AAlkylating+antineoplastic+agent&rft.atitle=Ifosfamide%2C+carboplatin+and+etoposide+%28ICE%29+combined+with+41.8+degrees+C+whole+body+hyperthermia+in+patients+with+refractory+sarcoma&rft.aulast=Wiedemann+GJ%2C+Robins+HI%2C+Gutsche+S%2C+Mentzel+M%2C+Deeken+M%2C+Katschinski+DM%2C+Eleftheriadis+S%2C+Crah%C3%A9+R%2C+Weiss+C%2C+Storer+B%2C+Wagner+T.&rft.au=Wiedemann+GJ%2C+Robins+HI%2C+Gutsche+S%2C+Mentzel+M%2C+Deeken+M%2C+Katschinski+DM%2C+Eleftheriadis+S%2C+Crah%C3%A9+R%2C+Weiss+C%2C+Storer+B%2C+Wagner+T.&rft.date=May+1996&rft.genre=article&rft_id=http%3A%2F%2Fcancerres.aacrjournals.org%2Fcgi%2Freprint%2F54%2F20%2F5346.pdf&rft_id=info%3Apmid%2F9081372&rft.issue=5&rft.jtitle=European+Journal+of+Cancer&rft.pages=888%E2%80%9392&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.volume=32A"></span></span></li> <li id="cite_note-3"><span class="mw-cite-backlink"><b><a href="http://en.wikipedia.org/wiki/Alkylating_antineoplastic_agent#cite_ref-3"><span class="cite-accessibility-label">Jump up </span>^</a></b></span> <span class="reference-text"><span class="citation journal">Goodman LS, Wintrobe MM, Dameshek W, Goodman MJ, Gilman AZ, McLennan MT (1946). "Nitrogen mustard therapy". <i>JAMA</i> <b>132</b> (3): 126–132. <a href="http://en.wikipedia.org/wiki/Digital_object_identifier" title="Digital object identifier">doi</a>:<a class="external text" href="http://dx.doi.org/10.1001%2Fjama.1946.02870380008004" rel="nofollow">10.1001/jama.1946.02870380008004</a>.</span><span class="Z3988" title="ctx_ver=Z39.88-2004&rfr_id=info%3Asid%2Fen.wikipedia.org%3AAlkylating+antineoplastic+agent&rft.atitle=Nitrogen+mustard+therapy&rft.au=Goodman+LS%2C+Wintrobe+MM%2C+Dameshek+W%2C+Goodman+MJ%2C+Gilman+AZ%2C+McLennan+MT&rft.aulast=Goodman+LS%2C+Wintrobe+MM%2C+Dameshek+W%2C+Goodman+MJ%2C+Gilman+AZ%2C+McLennan+MT&rft.date=1946&rft.genre=article&rft_id=info%3Adoi%2F10.1001%2Fjama.1946.02870380008004&rft.issue=3&rft.jtitle=JAMA&rft.pages=126%E2%80%93132&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.volume=132"></span></span></li> <li id="cite_note-Scott-4"><span class="mw-cite-backlink">^ <a href="http://en.wikipedia.org/wiki/Alkylating_antineoplastic_agent#cite_ref-Scott_4-0"><span class="cite-accessibility-label">Jump up to: </span><sup><i><b>a</b></i></sup></a> <a href="http://en.wikipedia.org/wiki/Alkylating_antineoplastic_agent#cite_ref-Scott_4-1"><sup><i><b>b</b></i></sup></a></span> <span class="reference-text"><span class="citation journal">Scott RB (1970). <a class="external text" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1819834" rel="nofollow">"Cancer chemotherapy--the first twenty-five years"</a>. <i>Br Med J.</i> <b>4</b> (5730): 259–265. <a href="http://en.wikipedia.org/wiki/Digital_object_identifier" title="Digital object identifier">doi</a>:<a class="external text" href="http://dx.doi.org/10.1136%2Fbmj.4.5730.259" rel="nofollow">10.1136/bmj.4.5730.259</a>. <a href="http://en.wikipedia.org/wiki/PubMed_Central" title="PubMed Central">PMC</a> <a class="external text" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1819834" rel="nofollow">1819834</a>. <a class="mw-redirect" href="http://en.wikipedia.org/wiki/PubMed_Identifier" title="PubMed Identifier">PMID</a> <a class="external text" href="http://www.ncbi.nlm.nih.gov/pubmed/4319950" rel="nofollow">4319950</a>.</span><span class="Z3988" title="ctx_ver=Z39.88-2004&rfr_id=info%3Asid%2Fen.wikipedia.org%3AAlkylating+antineoplastic+agent&rft.atitle=Cancer+chemotherapy--the+first+twenty-five+years&rft.aulast=Scott+RB&rft.au=Scott+RB&rft.date=1970&rft.genre=article&rft_id=%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC1819834&rft_id=info%3Adoi%2F10.1136%2Fbmj.4.5730.259&rft_id=info%3Apmc%2F1819834&rft_id=info%3Apmid%2F4319950&rft.issue=5730&rft.jtitle=Br+Med+J.&rft.pages=259%E2%80%93265&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.volume=4"></span></span></li> <li id="cite_note-5"><span class="mw-cite-backlink"><b><a href="http://en.wikipedia.org/wiki/Alkylating_antineoplastic_agent#cite_ref-5"><span class="cite-accessibility-label">Jump up </span>^</a></b></span> <span class="reference-text"><span class="citation journal">Gilman A (1963). "The initial clinical trial of nitrogen mustard". <i>Am J Surg.</i> <b>105</b> (5): 574–8. <a href="http://en.wikipedia.org/wiki/Digital_object_identifier" title="Digital object identifier">doi</a>:<a class="external text" href="http://dx.doi.org/10.1016%2F0002-9610%2863%2990232-0" rel="nofollow">10.1016/0002-9610(63)90232-0</a>. <a class="mw-redirect" href="http://en.wikipedia.org/wiki/PubMed_Identifier" title="PubMed Identifier">PMID</a> <a class="external text" href="http://www.ncbi.nlm.nih.gov/pubmed/13947966" rel="nofollow">13947966</a>.</span><span class="Z3988" title="ctx_ver=Z39.88-2004&rfr_id=info%3Asid%2Fen.wikipedia.org%3AAlkylating+antineoplastic+agent&rft.atitle=The+initial+clinical+trial+of+nitrogen+mustard&rft.au=Gilman+A&rft.aulast=Gilman+A&rft.date=1963&rft.genre=article&rft_id=info%3Adoi%2F10.1016%2F0002-9610%2863%2990232-0&rft_id=info%3Apmid%2F13947966&rft.issue=5&rft.jtitle=Am+J+Surg.&rft.pages=574%E2%80%938&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.volume=105"></span></span></li> <li id="cite_note-pmid10500495-6"><span class="mw-cite-backlink"><b><a href="http://en.wikipedia.org/wiki/Alkylating_antineoplastic_agent#cite_ref-pmid10500495_6-0"><span class="cite-accessibility-label">Jump up </span>^</a></b></span> <span class="reference-text"><span class="citation journal">McClean S, Costelloe C, Denny WA, Searcey M, Wakelin LP (June 1999). "Sequence selectivity, cross-linking efficiency and cytotoxicity of DNA-targeted 4-anilinoquinoline aniline mustards". <i>Anticancer Drug Des.</i> <b>14</b> (3): 187–204. <a class="mw-redirect" href="http://en.wikipedia.org/wiki/PubMed_Identifier" title="PubMed Identifier">PMID</a> <a class="external text" href="http://www.ncbi.nlm.nih.gov/pubmed/10500495" rel="nofollow">10500495</a>.</span><span class="Z3988" title="ctx_ver=Z39.88-2004&rfr_id=info%3Asid%2Fen.wikipedia.org%3AAlkylating+antineoplastic+agent&rft.atitle=Sequence+selectivity%2C+cross-linking+efficiency+and+cytotoxicity+of+DNA-targeted+4-anilinoquinoline+aniline+mustards&rft.aulast=McClean+S%2C+Costelloe+C%2C+Denny+WA%2C+Searcey+M%2C+Wakelin+LP&rft.au=McClean+S%2C+Costelloe+C%2C+Denny+WA%2C+Searcey+M%2C+Wakelin+LP&rft.date=June+1999&rft.genre=article&rft_id=info%3Apmid%2F10500495&rft.issue=3&rft.jtitle=Anticancer+Drug+Des.&rft.pages=187%E2%80%93204&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.volume=14"></span></span></li> <li id="cite_note-takimoto-7"><span class="mw-cite-backlink">^ <a href="http://en.wikipedia.org/wiki/Alkylating_antineoplastic_agent#cite_ref-takimoto_7-0"><span class="cite-accessibility-label">Jump up to: </span><sup><i><b>a</b></i></sup></a> <a href="http://en.wikipedia.org/wiki/Alkylating_antineoplastic_agent#cite_ref-takimoto_7-1"><sup><i><b>b</b></i></sup></a></span> <span class="reference-text">Takimoto CH, Calvo E. <a class="external text" href="http://www.cancernetwork.com/cancer-management-11/chapter03/article/10165/1402628" rel="nofollow">"Principles of Oncologic Pharmacotherapy"</a> in Pazdur R, Wagman LD, Camphausen KA, Hoskins WJ (Eds) <a class="external text" href="http://www.cancernetwork.com/cancer-management-11/" rel="nofollow">Cancer Management: A Multidisciplinary Approach</a>. 11 ed. 2008.</span></li> <li id="cite_note-pmid18289945-8"><span class="mw-cite-backlink"><b><a href="http://en.wikipedia.org/wiki/Alkylating_antineoplastic_agent#cite_ref-pmid18289945_8-0"><span class="cite-accessibility-label">Jump up </span>^</a></b></span> <span class="reference-text"><span class="citation journal">Cruet-Hennequart S, Glynn MT, Murillo LS, Coyne S, Carty MP (April 2008). <a class="external text" href="http://linkinghub.elsevier.com/retrieve/pii/S1568-7864%2808%2900003-7" rel="nofollow">"Enhanced DNA-PK-mediated RPA2 hyperphosphorylation in DNA polymerase eta-deficient human cells treated with cisplatin and oxaliplatin"</a>. <i>DNA Repair (Amst.)</i> <b>7</b> (4): 582–96. <a href="http://en.wikipedia.org/wiki/Digital_object_identifier" title="Digital object identifier">doi</a>:<a class="external text" href="http://dx.doi.org/10.1016%2Fj.dnarep.2007.12.012" rel="nofollow">10.1016/j.dnarep.2007.12.012</a>. <a class="mw-redirect" href="http://en.wikipedia.org/wiki/PubMed_Identifier" title="PubMed Identifier">PMID</a> <a class="external text" href="http://www.ncbi.nlm.nih.gov/pubmed/18289945" rel="nofollow">18289945</a>.</span><span class="Z3988" title="ctx_ver=Z39.88-2004&rfr_id=info%3Asid%2Fen.wikipedia.org%3AAlkylating+antineoplastic+agent&rft.atitle=Enhanced+DNA-PK-mediated+RPA2+hyperphosphorylation+in+DNA+polymerase+eta-deficient+human+cells+treated+with+cisplatin+and+oxaliplatin&rft.au=Cruet-Hennequart+S%2C+Glynn+MT%2C+Murillo+LS%2C+Coyne+S%2C+Carty+MP&rft.aulast=Cruet-Hennequart+S%2C+Glynn+MT%2C+Murillo+LS%2C+Coyne+S%2C+Carty+MP&rft.date=April+2008&rft.genre=article&rft_id=http%3A%2F%2Flinkinghub.elsevier.com%2Fretrieve%2Fpii%2FS1568-7864%2808%2900003-7&rft_id=info%3Adoi%2F10.1016%2Fj.dnarep.2007.12.012&rft_id=info%3Apmid%2F18289945&rft.issue=4&rft.jtitle=DNA+Repair+%28Amst.%29&rft.pages=582%E2%80%9396&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.volume=7"></span></span></li> <li id="cite_note-pmid18360630-9"><span class="mw-cite-backlink"><b><a href="http://en.wikipedia.org/wiki/Alkylating_antineoplastic_agent#cite_ref-pmid18360630_9-0"><span class="cite-accessibility-label">Jump up </span>^</a></b></span> <span class="reference-text"><span class="citation journal">Armand JP, Ribrag V, Harrousseau JL, Abrey L (June 2007). <a class="external text" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1936303" rel="nofollow">"Reappraisal of the use of procarbazine in the treatment of lymphomas and brain tumors"</a>. <i>Ther Clin Risk Manag</i> <b>3</b> (2): 213–24. <a href="http://en.wikipedia.org/wiki/Digital_object_identifier" title="Digital object identifier">doi</a>:<a class="external text" href="http://dx.doi.org/10.2147%2Ftcrm.2007.3.2.213" rel="nofollow">10.2147/tcrm.2007.3.2.213</a>. <a href="http://en.wikipedia.org/wiki/PubMed_Central" title="PubMed Central">PMC</a> <a class="external text" href="http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1936303" rel="nofollow">1936303</a>. <a class="mw-redirect" href="http://en.wikipedia.org/wiki/PubMed_Identifier" title="PubMed Identifier">PMID</a> <a class="external text" href="http://www.ncbi.nlm.nih.gov/pubmed/18360630" rel="nofollow">18360630</a>.</span><span class="Z3988" title="ctx_ver=Z39.88-2004&rfr_id=info%3Asid%2Fen.wikipedia.org%3AAlkylating+antineoplastic+agent&rft.atitle=Reappraisal+of+the+use+of+procarbazine+in+the+treatment+of+lymphomas+and+brain+tumors&rft.au=Armand+JP%2C+Ribrag+V%2C+Harrousseau+JL%2C+Abrey+L&rft.aulast=Armand+JP%2C+Ribrag+V%2C+Harrousseau+JL%2C+Abrey+L&rft.date=June+2007&rft.genre=article&rft_id=%2F%2Fwww.ncbi.nlm.nih.gov%2Fpmc%2Farticles%2FPMC1936303&rft_id=info%3Adoi%2F10.2147%2Ftcrm.2007.3.2.213&rft_id=info%3Apmc%2F1936303&rft_id=info%3Apmid%2F18360630&rft.issue=2&rft.jtitle=Ther+Clin+Risk+Manag&rft.pages=213%E2%80%9324&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.volume=3"></span></span></li> <li id="cite_note-isbn0-443-06527-6-10"><span class="mw-cite-backlink"><b><a href="http://en.wikipedia.org/wiki/Alkylating_antineoplastic_agent#cite_ref-isbn0-443-06527-6_10-0"><span class="cite-accessibility-label">Jump up </span>^</a></b></span> <span class="reference-text"><span class="citation book">Yasko, Joyce M.; Kirkwood, John M.; Lotze, Michael T. (1998). <i>Current cancer therapeutics</i>. Edinburgh: Churchill Livingstone. p. 3. <a href="http://en.wikipedia.org/wiki/International_Standard_Book_Number" title="International Standard Book Number">ISBN</a> <a href="http://en.wikipedia.org/wiki/Special:BookSources/0-443-06527-6" title="Special:BookSources/0-443-06527-6">0-443-06527-6</a>.</span><span class="Z3988" title="ctx_ver=Z39.88-2004&rfr_id=info%3Asid%2Fen.wikipedia.org%3AAlkylating+antineoplastic+agent&rft.aulast=Yasko%2C+Joyce+M.%3B+Kirkwood%2C+John+M.%3B+Lotze%2C+Michael+T.&rft.au=Yasko%2C+Joyce+M.%3B+Kirkwood%2C+John+M.%3B+Lotze%2C+Michael+T.&rft.btitle=Current+cancer+therapeutics&rft.date=1998&rft.genre=book&rft.isbn=0-443-06527-6&rft.pages=3&rft.place=Edinburgh&rft.pub=Churchill+Livingstone&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook"></span></span></li> <li id="cite_note-isbn3-540-66508-0-11"><span class="mw-cite-backlink"><b><a href="http://en.wikipedia.org/wiki/Alkylating_antineoplastic_agent#cite_ref-isbn3-540-66508-0_11-0"><span class="cite-accessibility-label">Jump up </span>^</a></b></span> <span class="reference-text"><span class="citation book">Schmit-Neuerburg, Klaus-Peter; Reiner Labitzke (2000). <i>Manual of Cable Osteosyntheses: History, Technical Basis, Biomechanics of the Tension Band Principle, and Instructions for Operation</i>. Berlin: Springer. p. 166. <a href="http://en.wikipedia.org/wiki/International_Standard_Book_Number" title="International Standard Book Number">ISBN</a> <a href="http://en.wikipedia.org/wiki/Special:BookSources/3-540-66508-0" title="Special:BookSources/3-540-66508-0">3-540-66508-0</a>.</span><span class="Z3988" title="ctx_ver=Z39.88-2004&rfr_id=info%3Asid%2Fen.wikipedia.org%3AAlkylating+antineoplastic+agent&rft.aulast=Schmit-Neuerburg%2C+Klaus-Peter%3B+Reiner+Labitzke&rft.au=Schmit-Neuerburg%2C+Klaus-Peter%3B+Reiner+Labitzke&rft.btitle=Manual+of+Cable+Osteosyntheses%3A+History%2C+Technical+Basis%2C+Biomechanics+of+the+Tension+Band+Principle%2C+and+Instructions+for+Operation&rft.date=2000&rft.genre=book&rft.isbn=3-540-66508-0&rft.pages=166&rft.place=Berlin&rft.pub=Springer&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook"></span></span></li> <li id="cite_note-isbn0-632-03998-1-12"><span class="mw-cite-backlink"><b><a href="http://en.wikipedia.org/wiki/Alkylating_antineoplastic_agent#cite_ref-isbn0-632-03998-1_12-0"><span class="cite-accessibility-label">Jump up </span>^</a></b></span> <span class="reference-text"><span class="citation book">Bailey, Christopher J.; Corner, Jessica (2001). <i>Cancer nursing: care in context</i>. Oxford: Blackwell Science. p. 214. <a href="http://en.wikipedia.org/wiki/International_Standard_Book_Number" title="International Standard Book Number">ISBN</a> <a href="http://en.wikipedia.org/wiki/Special:BookSources/0-632-03998-1" title="Special:BookSources/0-632-03998-1">0-632-03998-1</a>.</span><span class="Z3988" title="ctx_ver=Z39.88-2004&rfr_id=info%3Asid%2Fen.wikipedia.org%3AAlkylating+antineoplastic+agent&rft.au=Bailey%2C+Christopher+J.%3B+Corner%2C+Jessica&rft.aulast=Bailey%2C+Christopher+J.%3B+Corner%2C+Jessica&rft.btitle=Cancer+nursing%3A+care+in+context&rft.date=2001&rft.genre=book&rft.isbn=0-632-03998-1&rft.pages=214&rft.place=Oxford&rft.pub=Blackwell+Science&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook"></span></span></li> <li id="cite_note-isbn0-07-147781-0-13"><span class="mw-cite-backlink"><b><a href="http://en.wikipedia.org/wiki/Alkylating_antineoplastic_agent#cite_ref-isbn0-07-147781-0_13-0"><span class="cite-accessibility-label">Jump up </span>^</a></b></span> <span class="reference-text"><span class="citation book">Kutner, Jean S; Gonzales, Ralph (2006). <i>Current Practice Guidelines in Primary Care: 2007 (Current Practice Guidelines in Primary Care)</i>. McGraw-Hill Professional. p. 118. <a href="http://en.wikipedia.org/wiki/International_Standard_Book_Number" title="International Standard Book Number">ISBN</a> <a href="http://en.wikipedia.org/wiki/Special:BookSources/0-07-147781-0" title="Special:BookSources/0-07-147781-0">0-07-147781-0</a>.</span><span class="Z3988" title="ctx_ver=Z39.88-2004&rfr_id=info%3Asid%2Fen.wikipedia.org%3AAlkylating+antineoplastic+agent&rft.au=Kutner%2C+Jean+S%3B+Gonzales%2C+Ralph&rft.aulast=Kutner%2C+Jean+S%3B+Gonzales%2C+Ralph&rft.btitle=Current+Practice+Guidelines+in+Primary+Care%3A+2007+%28Current+Practice+Guidelines+in+Primary+Care%29&rft.date=2006&rft.genre=book&rft.isbn=0-07-147781-0&rft.pages=118&rft.pub=McGraw-Hill+Professional&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook"></span></span></li> <li id="cite_note-isbn0-7817-5492-5-14"><span class="mw-cite-backlink"><b><a href="http://en.wikipedia.org/wiki/Alkylating_antineoplastic_agent#cite_ref-isbn0-7817-5492-5_14-0"><span class="cite-accessibility-label">Jump up </span>^</a></b></span> <span class="reference-text"><span class="citation book">Pizzo, Philip A.; Poplack, David G. (2006). <i>Principles and practice of pediatric oncology</i>. Hagerstown, MD: Lippincott Williams & Wilkins. p. 313. <a href="http://en.wikipedia.org/wiki/International_Standard_Book_Number" title="International Standard Book Number">ISBN</a> <a href="http://en.wikipedia.org/wiki/Special:BookSources/0-7817-5492-5" title="Special:BookSources/0-7817-5492-5">0-7817-5492-5</a>.</span><span class="Z3988" title="ctx_ver=Z39.88-2004&rfr_id=info%3Asid%2Fen.wikipedia.org%3AAlkylating+antineoplastic+agent&rft.aulast=Pizzo%2C+Philip+A.%3B+Poplack%2C+David+G.&rft.au=Pizzo%2C+Philip+A.%3B+Poplack%2C+David+G.&rft.btitle=Principles+and+practice+of+pediatric+oncology&rft.date=2006&rft.genre=book&rft.isbn=0-7817-5492-5&rft.pages=313&rft.place=Hagerstown%2C+MD&rft.pub=Lippincott+Williams+%26+Wilkins&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Abook"></span></span></li> <li id="cite_note-15"><span class="mw-cite-backlink"><b><a href="http://en.wikipedia.org/wiki/Alkylating_antineoplastic_agent#cite_ref-15"><span class="cite-accessibility-label">Jump up </span>^</a></b></span> <span class="reference-text">N Engl J Med 2000;343;1350-4.</span></li> </ol> </div> </div> http://scholarpharma.blogspot.com/2014/02/alkylating-antineoplastic-agent-by.html1margipatel02@gmail.com (margipatel02@gmail.com)tag:blogger.com,1999:blog-8563020669307343167.post-1033188067301476507Sat, 09 Mar 2013 05:51:00 +00002013-03-08T21:53:52.779-08:00Clinical Trials<a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiGPQIeUHOprbDi1eIAlI31B8TOt8UOxcavdJzHHpENk-IWQ33M4vz5B2PBIsvgwdaFAeGhbINJg8NzHuY1WxT8S-uS3erTUKPyGMq11eRpl7vkhhWjXmI3x1T9Ge55fYh5EGsFqmNRnuLy/s1600/green-world.png" imageanchor="1" ><img border="0" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEiGPQIeUHOprbDi1eIAlI31B8TOt8UOxcavdJzHHpENk-IWQ33M4vz5B2PBIsvgwdaFAeGhbINJg8NzHuY1WxT8S-uS3erTUKPyGMq11eRpl7vkhhWjXmI3x1T9Ge55fYh5EGsFqmNRnuLy/s320/green-world.png" /></a> <b>Clinical Trials:</b> Medical clinical trials plays an important role in development of new drugs. These trials are conducted in three phases. <b>Introduction</b> Clinical trials are a means of developing new treatments and medications for diseases and conditions. There are strict rules for clinical trials, which are monitored by the National Institutes of Health and the U.S Food and Drug Administration. Clinical trials are also called clinical studies, research protocols or medical research and often compare one drug against another to see which is more effective, or the medicine or procedure in a specific demographic group or for a specific disease. <b>About Clinical Trials</b> <b> Why Participate in a Clinical Trial?</b> Participants in clinical trials can play a more active role in their health care, gain access to new research treatments before they are widely available and help others by contributing to medical research. <b>Where Do the Ideas for Trials Come from?</b> Ideas for clinical trials usually come from researchers. After researchers test new therapies or procedures in the laboratory and/or in animal studies, the treatments with the most promising test results are moved into clinical trials. During a trial, more and more information is gained about a new treatment, its risks and how well it may or may not work. W<b>ho Sponsors Clinical Trials?</b> Clinical trials are sponsored or funded by a variety of organizations or individuals such as physicians, medical institutions,foundations, voluntary medical-related groups and pharmaceutical companies, in addition to federal agencies such as the National Institutes of Health, the Department of Defense and the Department of Veteran’s Affairs. Trials can take place in a variety of locations, such as hospitals, universities, doctors’ offices or community clinics. <b>What is a Protocol?</b> A protocol is a study plan on which all clinical trials are based. The plan is carefully designed to safeguard the health of the participants as well as answer specific research questions. A protocol describes what types of people can participate in the trial; the schedule of tests, procedures, medications and dosages; and the length of the study. While in clinical trial, participants following a protocol are seen regularly by the research staff to monitor their health and to determine the safety and effectiveness of their treatment. <b>What is a Placebo?</b> A placebo is an inactive pill, liquid, or powder that has no treatment value. In clinical trials, experimental treatments are often compared with placebos to assess the treatment’s effectiveness. In some studies, the participants in the control group will receive a placebo instead of an active drug or treatment. <b>What is a Control or Control Group?</b> A control is the standard by which experimental observations are evaluated. In many clinical trials, one group of patients will be given an experimental drug or treatment, while the control group is given either a standard treatment for the illness or a placebo. <b>What are the Different Types of Clinical Trials?</b> Treatment trials test new treatments, new combinations of drugs, or new approaches to surgery or radiation therapy. Prevention trials look for better ways to prevent disease in people who have never had the disease or to prevent a disease from returning. These approaches may include medicine, vitamins, vaccines, minerals or lifestyle changes. Screening trials test the best way to detect certain diseases or health conditions. Quality of Life trials (or Supportive Caretrials) explore ways to improve comfort and the equality of life for individuals with a chronic illness. Classification of Clinical Trials There are three types of clinical trials – phase I, phase II and phase III – each one is designed to learn something different about a new medical treatment. <b>Phase I Trials</b> A phase I trial is the first test of a new treatment, and it uses the fewest number of patients (20-30 patients is typical). A phase I trial for a new drug is designed to determine the safety of the new drug, how to best administer it and the correct dosage (i.e., one that will minimize undesirable side effects). Because investigators are very interested in how the drug behaves in the body, patients in a phase I trial undergo frequent monitoring of their vital signs. Although drugs being tested in a phase I trial have shown promise in the laboratory, there is no guarantee that the drug will have any positive effects on a patient. Patients participating in a phase I drug trial help advance basic medical knowledge; they may or may not reap any personal benefits. <b>Phase II Trials</b> After a phase I clinical trial has determined the safe dose of a drug, it can enter a phase II trial, which begins the process of determining the drug’s effectiveness in treating a specific type of disease. Because a phase II trial involves more patients than a phase I trial, physicians also have a chance to observe any less common side effects associated with the drug. In a phase II trial, which can involve 100 patients or more, physicians carefully monitor patients for a drug effect. For example, in a clinical trial testing a drug to increase the number of platelets in the blood, patients would have frequent blood samples taken, but they might also undergo several physical exams and other tests. The high level of patient monitoring in a phase II trial can be very time-consuming, so patients should take this into account when considering a phase II trial. <div dir="ltr" style="text-align: left;" trbidi="on"> <br /></div>http://scholarpharma.blogspot.com/2013/03/clinical-trials.html0margipatel02@gmail.com (margipatel02@gmail.com)tag:blogger.com,1999:blog-8563020669307343167.post-1427999966577450109Mon, 04 Feb 2013 09:08:00 +00002013-02-04T01:08:39.538-08:00GSF2013 <b>The National Geographic Society</b> is one of the world's largest nonprofit scientific and educational organizations. Founded in 1888 to "increase and diffuse geographic knowledge," the Society's mission is to inspire people to care about the planet. It reaches more than 400 million people worldwide each month through its official journal, National Geographic, and other magazines; National Geographic Channel; television documentaries; music; radio; films; books; DVDs; maps; exhibitions; live events; school publishing programs; interactive media; and merchandise. National Geographic has funded more than 10,000 scientific research, conservation and exploration projects. For more information, visit www.nationalgeographic.com. As the non-commercial, educational outreach arm of the National Geographic Society, National Geographic Education pursues two primary goals: to bring National Geographic's rich resources for learning to the largest possible audience of educators worldwide; and to catalyze educational change that will bring National Geographic's vision of a geo-literate society to life. National Geographic Education creates compelling resources for teaching and learning, provides educators with transformative learning experiences, and advocates for improved education in geography, the environmental sciences, and the other disciplines that are critical to geo-literacy. Join the 5.5 million annual visitors at NatGeoEd.org to learn more about National Geographic Education and get involved in building a more geo-literate society <b>& </b> <b>Scientific American</b> is at the heart of Nature Publishing Group's (NPG's) consumer media division, meeting the needs of the general public. Founded in 1845, Scientific American is the longest continuously published magazine in the U.S. and the leading authoritative publication for science in the general media. Together with scientificamerican.com and 14 local-language editions around the world, it reaches more than 5 million opinion-leading citizens, public and private sectors influential, educators and scientists. Scientific American won a 2011 National Magazine Award for General Excellence. Other titles include Scientific American MIND in the US and 14 local-language editions worldwide. Scientific American is committed to promoting science, technology, engineering and mathematics (STEM) education, and to promoting wider engagement among the public and scientists. In September 2010 NPG became a member of Change the Equation, a CEO-led initiative to cultivate widespread literacy in STEM in the U.S., as part of President Obama's "Educate to Innovate" campaign. In 2011 Scientific American launched several programs in support of the initiative's goals. Bring Science Home, an ongoing weekly program, provides parents and school age children with simple projects that explain basic science principles they can do at home in just a few minutes. In Citizen Science, Scientific American has created an online platform for children and adults to participate in ongoing scientific research conducted by major research institutions. Scientific American, in partnership with The Zooniverse,launched the whale-song project, Whale FM, which enables "citizen scientists" to help marine researchers better understand how killer whales and pilot whales communicate. With the 1,000 Scientists in 1,000 Days program, Scientific American has created a portal where educators can connect with scientists who have agreed to volunteer their time to benefit STEM education, perhaps by volunteering in a classroom or explaining the latest in research. To encourage science-literacy in children, Scientific American launched our popular blog, Budding Scientist, lead by editor Anna Kutchment. Scientific American is also a media sponsor and participant in the biennial USA Science & Engineering Festival. In 2012, Scientific American launched the annual Science in Action prize, powered by the Google Science Fair. This prize honors a project that could make a practical difference by addressing an environmental, health or resources problem in the lives of a community. <a href="https://www.googlesciencefair.com/en/2013/"></a> <div dir="ltr" style="text-align: left;" trbidi="on"> <br /></div>http://scholarpharma.blogspot.com/2013/02/gsf2013.html1margipatel02@gmail.com (margipatel02@gmail.com)tag:blogger.com,1999:blog-8563020669307343167.post-2485611801722769326Sun, 12 Aug 2012 14:23:00 +00002012-08-12T07:23:09.032-07:00Ion exchange resin and its application in pharmaceutical dosage forms, and drug delivery systems.Ion exchange resins are cross linked polymers of polystyrene, up on which a negatively charged or a positively charged functional group can be added to get an anion exchange resin (Resin- )or a cation exchange resin Resin +(Resin + Or Resin- ). When these resins are mixed with drug molecule which has a negative charge in its one or more functional group as a result of polarity, or as in salt form, or as a result of resonance, such a drug can form a complex with a resin as follow.<br /> <br /> 1.) Resin + Drug-<br /> 2.) Resin- Drug+<br /> <br /> *The resulting resin drug complex stability depends on how strong are the acidic or basic functional groups on resin, stronger functional group result in to formation of very stable resin drug complex, and vice a versa , both has its applications in sustained release drug delivery systems, a resin with strong acidic or basic functional group tend to provide a much more delayed drug release, where drug release is bit faster with weak acidic and basic functional group resins.<br /> <br /> When Resin- Drug+ or Resin + Drug- complex (drug resinate ) comes in contact with acid(in stomach) or base(in intestine), it start releasing drug molecule in exchange of similar charged ion for example if drug molecule is positively charged, then it is released from Resin- Drug+ complex when it come in contact with Hydrogen Ion( H+) , similarly a Resin + Drug- or basic drug resin complex will start releasing drug when it comes in contact with basic ions ( in intestine ) OH – NH3- .<br /> Release of drug molecule from Resin +Drug complex takes place due to higher concentration of replacing ions (H+ , or OH – NH3- ).<br /> <br /> <br /> <b>Masking Taste of drug with ion exchange resin:</b><br /> There are some drugs which are very bitter in taste like Bromhexin and Quinine, patients has very low acceptability for such drugs some time patients vomit and expelling all of the consumed dose which may result in to dosing error, therefore when such drugs are formulated with ion exchange resins which binds such drugs they do not release drug on taste buds over tongue as a result taste of drug is masked, and when it come in contact with gastric acid bromhexin is released in to gut.<br /> <br /> <b>Sustained-release drug delivery system:</b><br /> Ion exchange resins may not alone give capability to formulate it in to a sustained release dosage form , to make it a good sustained release drug delivery system , proper selection of resin is important a resin with strong acidic or basic functional group provides strong complexation with drug therefore are good candidates for delayed drug release, likewise when early release is intended a weaker acidic or basic functional group resins are useful . Drug resinate is also required to be coated with semipermiable film forming polymers, as drug resinate complex can not be solely relied up on for the intended use. ( ethylcellulose ). In order to maintained the sustained release property of ion exchange resin drug complex it is pretreated with polyethylene glycol so that it do not swell and break open the film coating when it come in contact with gastric juice.<br /> <br /> Ion exchange resins are required to be washed with, suitable organic solvent, to remove residual organic or chemical impurities in ion exchange resin, followed by washing with purified water, and regeneration if required, before using for actual process. Ion exchange resin are required to comply with requirements listed in 21 CFR 173.25 by US FDA.<br /> <br /> Ion exchange resins have many other applications in pharmaceutical dosage form and drug delivery systems like , localized drug release, stabilization of drug molecule for chemical degradation .<br /> Ion exchange resins are widely used in pharmaceutical industry for purification or raw water and in preparation of water for pharmaceutical use. <br /> <br /> <b>-Rajarshi Nareshkumar Patel</b>http://scholarpharma.blogspot.com/2012/08/ion-exchange-resin-and-its-application.html5margipatel02@gmail.com (margipatel02@gmail.com)tag:blogger.com,1999:blog-8563020669307343167.post-6878861048754391714Sun, 12 Aug 2012 14:18:00 +00002012-08-12T07:18:19.498-07:00Novel Drugs: Cancer Chemotherapy Using Nanoparticles developed with Nanotechnology May Reduce Harmful Side Effects of Antineoplastic Agents.Chemotherapy for cancer is most of the time associated with one or the other harmful side effect of antineoplastic drugs as these chemotherapeutic drugs themselves are very cytotoxic, i.e. they damage normal cells too.<br /> Antineoplastic drugs bring about their anticancer action by inhibiting cancerour cells growth by virtue of alkylation of nucleotides in cancerous cells or by inhibition of folic acid uptake by cancerous cells or by inhibiting cell division by binding with tubulin and microtubulin in a cancerous cells, it is likely that these drug are also absorbed in to normal tissues, leading to untoward serious cytotoxic effects , like kidney damage and nerve damage in chemotherapy with cisplatin, a drug of choice in most of anticancer chemotherapies.<br /> <br /> A new drug delivery technique is being studied which uses Nanotechnology to deliver a cytotoxic drugs specifically directly in to the cancer cells , such drug delivery technique will be able to provide an efficient cancer chemotherapy that do not have much side effects as they pose today , it was observed that with nanoparticle drug delivery system the concentration of drug required to kill the cancerous cell is lesser than required in conventional chemotherapy therapy. As the drug is absorbed efficiently in to targeted cells and also drug is protected from degradation in blood stream , certain class of the anticancerdrugs are very unstable and stay in plasma for a very little time, therefor to achieve the required effect a higher concentration of drug may be required to be administrated.<br /> <br /> Nanotechnology drug delivery system involves placing an anticancer drug in to a tiny particles known as nanoparticles which recognize cancerous cells and deliver the drug only to cancerous cells , as nanoparticles are very minute particles (1 nm to 100 nanometer) , the dose of drug required to kill the cancerous cells were also found to be very low as compared to conventional therapy . As the required effective dose it self gets reduced than conventional therapy , the harmful effect of anticancer drug are also likely to be reduced.<br /> <br /> A team of scientists from the Massachusetts Institute of Technology and Brigham and Women's Hospital conducted study. They stored an prodrug of cisplatin (which is used in most of cancer chemotherapies) within nanoparticles which they developed to target a specific protein in cancerous cells in prostate gland.<br /> After these prodrug loaded nanoparticles were absorbed by cancerous cells the prodrug was released in to the cancerous cells and was converted in to an active form . The team demonstrated that these prodrug carrying nanoparticles were able to kill cancer cells in culture more efficiently than the drug alone.<br /> <br /> Study was conducted by researchers, led by Dr. Omid Farokhzad and Dr. Stephen Lippard, to study nanoparticle drug delivery system for an effective and safer option for chemotherapy in living animals. Their research work is published in Proceedings of the National Academy of Sciences, in Jan 2011 issue of the journal, the study was funded in part by NIH’s National Cancer Institute (NCI) and National Institute for Biomedical Imaging and Bioengineering (NIBIB).<br /> <br /> By applying this drug delivery by nanoparticles they were able to shrink tumors in mice with smaller doses of the drug to reduce harmful side effects. Only 30% of the dose of prodrug of cisplatin was required to diminish the tumor by using the drug carrying nanoparticles, than that of standard dose of cisplatin as such.<br /> Researchers initially studied different doses of nanoparticle bound drug in rats and mice, both the types of animals maintained their body weight and survived at higher doses of the drug when drug was delivered using nanoparticles than when injected without nanoparticles. It was also found that the kidney damage was less in rats which received the nanoparticle bound drug.<br /> <br /> Also it was found that binding nanoparticles provided greater stability of cisplatin prodrug in blood stream than that of injected alone , after one hour about 77 % of prodrug was found in blood stream when it was delivered using nanoparticles compared to only 16% available drug in case of drug delivered without nanoparticles, cispaltin is very unstable drug and remains in blood for very short time , which calls for more dose to get the desired effect. <br /> <br /> Rajarshi Patelhttp://scholarpharma.blogspot.com/2012/08/novel-drugs-cancer-chemotherapy-using.html2margipatel02@gmail.com (margipatel02@gmail.com)tag:blogger.com,1999:blog-8563020669307343167.post-2296009307191746537Sun, 12 Aug 2012 14:15:00 +00002012-08-12T07:15:04.051-07:00Kidney transplant will see more success rate than earlier.Patients suffering from kidney failure are required to go for treatment like regular dialysis and kidney transplant, and that to be not all kidney transplants are successful , 1 out of every 3 kidney transplants are rejected by patients body (because of patients immune system) , it is because of the human body recognizes difference between its own body tissue and other persons body tissue and human body reject others persons body tissue by producing antibodies against the transplanted tissue , ultimately damaging and rejecting the transplanted kidney.<br /> <br /> Dr. Robert A. Montgomery and his team from the Johns Hopkins University School of Medicine have found new technique , which has shown promising method which has greatly lowered the kidney rejection and has done kidney transplants successfully with their method.<br /> <br /> They identified that there is an antigen on cells in human called as human leukocyte antigen, a person sensitized by human leukocyte antigen (HLA sensitized ) help human immune system to identify its own body tissue and incoming foreign tissue and trigger antibodies against transplanted kidney transplant and further leads to kidney rejection.<br /> <br /> Therefore they developed a method to desensitize patients by filtering out anti-HLA antibodies they removed the anti-HLA antibodies from patient’s body by process of plasmapheresis. Patients were given<br /> Low-dose intravenous immune globulin (antibody preparation made from pooled donor blood) as substitute for anti-HLA antibodies. The procedure of plasmapheresis was repeated several times before the actual kidney transplant was done , these patients were also given other immuno suppressant drugs which are normally given before kidney transplant.<br /> <br /> More than 80% of the patients which received kidney transplant and plasmapheresis treatment were still alive after 8 years. Compared to observed lower life period for patients on either dialysis or HLA compatible kidney transplant ad dialysis.<br /> The method is bit costly but is cost effective compared to the total other costs of regular dialysis are considered in kidney failure patients, and success rate.<br /> <b><br /> What is plasmapheresis:</b><br /> <br /> Plasmapheresis is a method of removing toxic or unwanted component from blood , by removing part of blood out of body and processing it in centrifuge to separate blood cells and plasma , the plasma containing toxic or unwanted antibodies is discarded and is replaced with donor plasma , albumin , or 70% albumin and 30% saline , a suitable anticoagulant drug is given to patient before the plasmapheresis procedure .http://scholarpharma.blogspot.com/2012/08/kidney-transplant-will-see-more-success.html0margipatel02@gmail.com (margipatel02@gmail.com)tag:blogger.com,1999:blog-8563020669307343167.post-7581203812738492347Sun, 08 Jul 2012 06:33:00 +00002012-07-07T23:33:08.808-07:00'India ready to make it big in outsourcing of medical devices''India ready to make it big in outsourcing of medical devices'<br /> <br /> <br /> <br /> India is now in the limelight for its expertise in the medical devices space. The industry's inherent engineering strengths is being recognized by global majors who are looking to tap the emerging market opportunities to augment growth. This is where Bangalore-based MedVed sets up an advanced facility here, which has designed and developed high quality, reasonable priced implantable medical devices for cardiac rhythm management. The company's 'Stellar' brand for single and dual pacemakers, cardiac leads, pacing system analyzers will now revolutionize the heart surgery management. Dinesh Puri, chairman and managing director, MediVed Innovations Pvt Ltd provides an overview of the opportunities, business potential in the segment in a discussion with Nandita Vijay. Excerpts:<br /> <br /> How do you see India emerging as a hub for contract design, manufacture of medical devices?<br /> India is well placed in the outsourced contract design, development and manufacturing space because of its engineering capabilities in a wide spectrum of areas. Typically, there are two market opportunities in contract design and development of medical devices. One is that companies in the US and Europe can offload a whole range of existing medical device products to India to maximize the cost advantage. India has been proving to be a reliable and dependable source for this capability. The second is that global companies can look at India as a hub in the Asian region to undertake contract design, develop, manufacture and package the medical devices.<br /> <br /> What according to you are the visible trends in this space?<br /> A visible trend is that all international companies in the wake of the global economic slow down are looking to tap opportunities in the emerging markets. These are the markets of the future. Companies in the West are transforming business models to cater to the needs of the emerging markets which make up 4/5th of the global demand.<br /> <br /> In the wake of these opportunities, what are the efforts taken by global cos to make the most of the situations?<br /> The companies have begun to re-device the business strategy primarily because emerging markets are price sensitive. Therefore companies would look at alliances and joint ventures with Indian enterprises in these regions. In the US, the issue is 'performance over price' as against India where it is 'price over utility'. Therefore international companies need to look at the 'design-to-cost' factor to make medical devices available in India. This is where global majors will now have to look at design and manufacturing hubs in Asia and India, in particular, to tap the quality-cost advantage which will help improve gross margins. There is need for innovative thinking and India is now building its capability to be a platform for such prospects.<br /> <br /> What are the challenges before medical devices cos to generate business?<br /> The challenge for medical device companies is to raise funds and be able to repay within a realistic time frame. In this business, cycle time is longer. Therefore, both the investor and management have to be patient. There is also the issue of global sourcing of raw materials and dealing with imports because of inconsistent levy of import duty on raw materials which is higher than the finished products. Therefore, we need to be able to raise investments with a realistic time frame and calibrate expectations of time.<br /> <br /> Could you tell us how MediVed has grown since its inception two years ago?<br /> MediVed is in the league of the top six world-class medical devices companies. It has the advanced infrastructure and technical competence to offer services at a competitive cost. Our capability covers design, development of electro mechanical diagnostic and therapeutics devices besides implantable devices and active implantable like pacemakers. The company is currently doing five pilot projects for customers in the US. The assignments are in various phases of development. The projects are proving to test the capability in development of complex devices ranging from surgical to dental and diagnostics equipment apart from implantable devices. But, since pilots take a long time to convert into revenues, we are keen to tap the contract business space. By 2011, we hope to garner a turnover of Rs 150-crore which will be generated with contract assignments and the 'Stellar' brand pacemakers. The two opportunities could chip in a 50:50 revenue generation. The business opportunity in medical devices globally is close to $200 billion.<br /> <br /> How is MediVed positioned to tap the opportunities?<br /> MediVed has the expertise in medical device engineering, design and prototype. It can provide the proof of concept in the lab study and later scale up manufacture.<br /> <br /> We are gearing up to offer our expertise across all segments in medical devices from electrical-electronics-mechanical engineering to software. These include high precision machining of components, sub assemblies to printed circuit boards assembling, sourcing of implantable grade materials and sterile packaging, global sourcing of bio gradable materials which are implantable grade materials steel, noble metals, novel biomaterials like nitinol, polymers, silicones, epoxy of medical grade. This is possible because of our state-of-the-art ISO 13485 compliant in-house multi disciplinary engineering and manufacture infrastructure that includes micro electronics, polymer sciences, bio mechanical, laser welding-hermetic sealing which is supported by 100,000 class clean room and complex device assembly areas. We have the expertise to provide the required regulatory compliance documentation for medical devices manufacturing quality management systems.<br /> <br /> What is the future of medical devices industry?<br /> The future holds immense potential for the medical devices industry. This is because of the strong growth of the healthcare space. India can score over China in the medical devices space and grab the contract design and development orders. The country has a sound record in adherence to IPR which is vital for medical devices because it follows English law which is also referred to as the contract law of the Commonwealth countries. International Courts uphold the English law.<br /> <br /> There is multi-disciplinary R&D efforts and engineering capability in multiple sciences of electronics, chip design, software mechanical and medical engineering which are complex. The country has already made a mark in pharmaceuticals, development of new chemical entities and clinical research. The time has now come for India to take its place in the medical devices space. This medical device engineering opportunity is bigger than the Information Technology (IT) boom and we need to capitalisehttp://scholarpharma.blogspot.com/2012/07/india-ready-to-make-it-big-in.html0margipatel02@gmail.com (margipatel02@gmail.com)tag:blogger.com,1999:blog-8563020669307343167.post-280896708772466807Sun, 08 Jul 2012 06:30:00 +00002012-07-07T23:30:16.188-07:00ResearchIndia-Canada to foster joint R&D projects in biotech, health research, medical devicesIndia-Canada to foster joint R&D projects in biotech, health research, medical devices<br /> <br /> <br /> Under the Canada-India agreement for scientific and technological cooperation, India and Canada will soon foster joint research and development (R&D) projects in areas of biotechnology, health research, pharmaceuticals, medical devices and nanotechnology as it applies to these sectors.<br /> <br /> The key objectives of this joint programme are to encourage domestic competitiveness through the transfer of technology and knowledge resulting from international S&T partnerships; to foster international S&T partnerships and collaborative research with an emphasis on industrial outcomes; to accelerate the commercialization of R&D that would benefit Canada and the partner country, through international partnerships, with a focus on small and medium-sized enterprises; to access international technologies for Canadian enterprises; to promote Canadian R&D capacity and Canada as a destination for foreign technology-based investments; to encourage the mobility of researchers and to promote Canada as a career destination for foreign researchers and highly qualified personnel; and to strengthen overall bilateral S&T relations.<br /> <br /> The Department of Biotechnology (DBT) will be the implementing organization on the Indian side, while the International Science and Technology Partnerships Canada (ISTPCanada), a non-governmental organization will be implementing the project on the Canadian side.<br /> <br /> This Canada-India programme aims to foster and support the development of collaborative R&D projects that bring together companies, research organizations, academics and other collaborators from both countries for the joint development of innovative products or processes. It aims to stimulate innovative R&D projects (engaging small-to-medium-sized companies and/or larger, well established firms) that address a specific market need or challenge; demonstrate high industrial relevance and commercial potential; and aim to deliver benefit to all participants, and more broadly, to both nations. These projects help participants to become more competitive by developing global research-based alliances with the potential to foster increased or expanded international R&D collaboration.<br /> <br /> Eligible Indian applicants for this programme include researchers and managers of Indian companies, academic institutions, research hospitals or other R&D institutions (including not-for-profit research institutes recognized by DBT) that are headquartered and operate in India.<br /> <br /> Eligible Canadian applicants must be researchers or managers of for-profit companies that operate and are headquartered in Canada. Canadian subsidiaries of companies headquartered outside of Canada are typically not eligible for support. However, as ‘benefit to Canada’ is a key objective and among the most important selection criteria, ISTPCanada may grant an exception to such subsidiaries if they have R&D facilities in Canada and can demonstrate that Canada will accrue clear economic benefit from the bilateral R&D project. Academic institutions, research hospitals, other institutes or research associations are strongly encouraged to participate in the projects as co-investigators.<br /> <br /> Each proposal must include an eligible lead from Canada and India. Although it is not mandatory, projects that engage a technology developer and a technology end-user/first customer are strongly encouraged.http://scholarpharma.blogspot.com/2012/07/india-canada-to-foster-joint-r-projects.html1margipatel02@gmail.com (margipatel02@gmail.com)tag:blogger.com,1999:blog-8563020669307343167.post-4112747964346217494Sun, 01 Apr 2012 05:57:00 +00002012-03-31T22:57:34.085-07:00aldolase-catalyzed process for enantioselective synthesis of statin intermediatesDevelopment of an efficientscalableDevelopment of an efficient, scalable, aldolase-catalyzed process for enantioselective synthesis of statin intermediates<html xmlns:v="urn:schemas-microsoft-com:vml" xmlns:o="urn:schemas-microsoft-com:office:office" xmlns:w="urn:schemas-microsoft-com:office:word" xmlns:m="http://schemas.microsoft.com/office/2004/12/omml" xmlns="http://www.w3.org/TR/REC-html40"><br /> <br /> <head><br /> <meta http-equiv=Content-Type content="text/html; charset=windows-1252"><br /> <meta name=ProgId content=Word.Document><br /> <meta name=Generator content="Microsoft Word 12"><br /> <meta name=Originator content="Microsoft Word 12"><br /> <link rel=File-List href="Development%20of%20an%20efficien1_files/filelist.xml"><br /> <link rel=Edit-Time-Data href="Development%20of%20an%20efficien1_files/editdata.mso"><br /> <br /> <link rel=dataStoreItem href="Development%20of%20an%20efficien1_files/item0001.xml" target="Development%20of%20an%20efficien1_files/props0002.xml"><br /> <link rel=themeData href="Development%20of%20an%20efficien1_files/themedata.thmx"><br /> <link rel=colorSchemeMapping href="Development%20of%20an%20efficien1_files/colorschememapping.xml"><br /> <br /> <style>  </style><br /> <br /> <br /> </head><br /> <br /> <body lang=EN-US link=blue vlink=purple style='tab-interval:.5in'><br /> <br /> <div class=Section1><br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal;mso-outline-level:1'><b><span style='font-size:24.0pt; font-family:"Times New Roman","serif";mso-fareast-font-family:"Times New Roman"; mso-font-kerning:18.0pt'>Development of an efficient, scalable,<br /> aldolase-catalyzed process for enantioselective synthesis of statin<br /> intermediates<o:p></o:p></span></b></p><br /> <ol start=1 type=1> <li class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal;mso-list:l5 level1 lfo1;tab-stops:list .5in'><span style='font-size:12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family: "Times New Roman"'><a href="http://www.pnas.org/search?author1=William+A.+Greenberg&sortspec=date&submit=Submit">William<br /> A. Greenberg</a> <a href="http://www.pnas.org/content/101/16/5788.long#fn-1">*</a>, <o:p></o:p></span></li> <li class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal;mso-list:l5 level1 lfo1;tab-stops:list .5in'><span style='font-size:12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family: "Times New Roman"'><a href="http://www.pnas.org/search?author1=Alexander+Varvak&sortspec=date&submit=Submit">Alexander<br /> Varvak</a>, <o:p></o:p></span></li> <li class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal;mso-list:l5 level1 lfo1;tab-stops:list .5in'><span style='font-size:12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family: "Times New Roman"'><a href="http://www.pnas.org/search?author1=Sarah+R.+Hanson&sortspec=date&submit=Submit">Sarah<br /> R. Hanson</a>, <o:p></o:p></span></li> <li class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal;mso-list:l5 level1 lfo1;tab-stops:list .5in'><span style='font-size:12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family: "Times New Roman"'><a href="http://www.pnas.org/search?author1=Kelvin+Wong&sortspec=date&submit=Submit">Kelvin<br /> Wong</a>, <o:p></o:p></span></li> <li class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal;mso-list:l5 level1 lfo1;tab-stops:list .5in'><span style='font-size:12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family: "Times New Roman"'><a href="http://www.pnas.org/search?author1=Hongjun+Huang&sortspec=date&submit=Submit">Hongjun<br /> Huang</a>, <o:p></o:p></span></li> <li class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal;mso-list:l5 level1 lfo1;tab-stops:list .5in'><span style='font-size:12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family: "Times New Roman"'><a href="http://www.pnas.org/search?author1=Pei+Chen&sortspec=date&submit=Submit">Pei<br /> Chen</a>, and <o:p></o:p></span></li> <li class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal;mso-list:l5 level1 lfo1;tab-stops:list .5in'><span style='font-size:12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family: "Times New Roman"'><a href="http://www.pnas.org/search?author1=Mark+J.+Burk&sortspec=date&submit=Submit">Mark<br /> J. Burk</a> <a href="http://www.pnas.org/content/101/16/5788.long#fn-1">*</a><br /> <br /> <o:p></o:p></span></li> </ol><br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal'><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'><a href="http://www.pnas.org/content/101/16/5788.long">-</a> Author Affiliations<o:p></o:p></span></p><br /> <ol style='margin-top:0in' start=1 type=1> <li class=MsoNormal style='margin-bottom:0in;margin-bottom:.0001pt;line-height: normal;mso-list:l2 level1 lfo2;tab-stops:list .5in'><a name=aff-1></a><i><span style='font-size:12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family: "Times New Roman"'>Diversa Corporation, 4955 Directors Place, San Diego,<br /> CA 92121<o:p></o:p></span></i></li> </ol><br /> <ol start=1 type=1> <li class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal;mso-list:l3 level1 lfo3;tab-stops:list .5in'><span style='font-size:12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family: "Times New Roman"'>Edited by Barry M. Trost, Stanford University,<br /> Stanford, CA, and approved February 19, 2004 (received for review November<br /> 14, 2003) <o:p></o:p></span></li> </ol><br /> <p class=MsoNormal style='margin-bottom:0in;margin-bottom:.0001pt;line-height: normal'><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'> <o:p></o:p></span></p><br /> <p class=MsoNormal style='margin-bottom:0in;margin-bottom:.0001pt;line-height: normal'><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'><a href="http://www.pnas.org/content/101/16/5788.long#sec-1" title="Materials and Methods">Next Section</a><o:p></o:p></span></p><br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal;mso-outline-level:2'><b><span style='font-size:18.0pt; font-family:"Times New Roman","serif";mso-fareast-font-family:"Times New Roman"'>Abstract<o:p></o:p></span></b></p><br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal'><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'>A process is reported for efficient,<br /> enantioselective production of key intermediates for the common chiral side<br /> chain of statin-type cholesterol-lowering drugs such as Lipitor (atorvastatin)<br /> and Crestor (rosuvastatin). The process features a one-pot tandem aldol<br /> reaction catalyzed by a deoxyribose-5-phosphate aldolase (DERA) to form a<br /> 6-carbon intermediate with installation of two stereogenic centers from<br /> 2-carbon starting materials. An improvement of almost 400-fold in volumetric<br /> productivity relative to the published enzymatic reaction conditions has been<br /> achieved, resulting in a commercially attractive process that has been run on<br /> up to a 100-g scale in a single batch at a rate of 30.6 g/liter per h. Catalyst<br /> load has been improved by 10-fold as well, from 20 to 2.0 wt % DERA. These<br /> improvements were achieved by a combination of discovery from environmental DNA<br /> of DERAs with improved activity and reaction optimization to overcome substrate<br /> inhibition. The two stereogenic centers are set by DERA with enantiomeric<br /> excess at >99.9% and diastereomeric excess at 96.6%. In addition,<br /> down-stream chemical steps have been developed to convert the enzymatic product<br /> efficiently to versatile intermediates applicable to preparation of<br /> atorvastatin and rosuvastatin. <o:p></o:p></span></p><br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal'><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'>Biocatalysis has received attention<br /> recently as a tool of enormous potential for the synthesis of pharmaceutical,<br /> industrial, and agricultural chemicals and intermediates (<a href="http://www.pnas.org/content/101/16/5788.long#ref-1">1</a>–<a href="http://www.pnas.org/content/101/16/5788.long#ref-5">5</a>). To capitalize<br /> further on this potential, enzymes must demonstrate not only superior<br /> performance characteristics such as high enantioselectivity and low catalyst<br /> loading but also cost-effectiveness and scalability. A successful industrial<br /> biocatalytic process requires enzymes that can be produced cheaply in kilogram<br /> quantities and are stable and active at very high substrate and product<br /> concentrations, frequently in the presence of organic solvents. Although many<br /> remarkable biocatalytic transformations have been reported on the<br /> milligram-to-gram scale, especially in light of recent advances in directed<br /> evolution and high-throughput screening for novel enzymes (<a href="http://www.pnas.org/content/101/16/5788.long#ref-6">6</a>–<a href="http://www.pnas.org/content/101/16/5788.long#ref-8">8</a>), the number of<br /> processes that have been applied on an industrial scale remains limited (<a href="http://www.pnas.org/content/101/16/5788.long#ref-5">5</a>, <a href="http://www.pnas.org/content/101/16/5788.long#ref-9">9</a>). This is<br /> especially true for biocatalytic processes involving formation of carbon–carbon<br /> bonds. <o:p></o:p></span></p><br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal'><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'>The aldol reaction is an extremely<br /> useful transformation that allows the formation of new carbon–carbon bonds and<br /> the introduction of up to two new stereocenters into the product. Controlling<br /> the stereochemistry of aldol reactions can be challenging and has been an area<br /> of intense research. Although several elegant asymmetric methods have been<br /> developed (<a href="http://www.pnas.org/content/101/16/5788.long#ref-10">10</a>–<a href="http://www.pnas.org/content/101/16/5788.long#ref-12">12</a>), there<br /> remains a need for additional methods, and in recent years enzyme-catalyzed<br /> approaches using aldolases have received attention as alternatives to chemical<br /> methodologies (<a href="http://www.pnas.org/content/101/16/5788.long#ref-13">13</a>).<br /> <o:p></o:p></span></p><br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal'><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'>Several years ago, Wong and<br /> coworkers (<a href="http://www.pnas.org/content/101/16/5788.long#ref-14">14</a>,<br /> <a href="http://www.pnas.org/content/101/16/5788.long#ref-15">15</a>) reported<br /> unprecedented one-pot tandem aldol reactions catalyzed by a<br /> deoxyribose-5-phosphate aldolase (DERA), in which 2 eq of acetaldehyde were<br /> added in sequence to 2-carbon aldehyde acceptors to afford six-membered lactol<br /> derivatives (<a href="http://www.pnas.org/content/101/16/5788.long#F1">Fig. 1</a>).<br /> Because the DERA-catalyzed reaction is an equilibrium process, the intermediate<br /> 4-carbon adduct (<a href="http://www.pnas.org/content/101/16/5788.long#F1">Fig.<br /> 1</a>) is reversibly formed under the reaction conditions. The second condensation<br /> between this intermediate and a second equivalent of acetaldehyde drives the<br /> equilibrium favorably because of the stability of the cyclized lactol form of<br /> the product. The authors noted the structural similarity of the enzymatic<br /> products to the lactone moiety (and its interchangeable 3,5-dihydroxy acid<br /> form) of the cholesterol-lowering 3-hydroxy3-methylglutaryl (HMG)-CoA reductase<br /> inhibitors mevastatin and lovastatin. Today, HMG-CoA reductase inhibitors<br /> (collectively known as statins) have worldwide sales of approximately $20<br /> billion, led by Pfizer's Lipitor (atorvastatin), the world's top-selling drug.<br /> Atorvastatin and AstraZeneca's newly approved Crestor (rosuvastatin) (<a href="http://www.pnas.org/content/101/16/5788.long#F2">Fig. 2</a>) are<br /> completely synthetic molecules, unlike the earlier generation of statins that<br /> were fungal metabolites or semisynthetic derivatives thereof. The synthetic<br /> statins share the chiral 3,5-dihydroxy acid side chain also found in the<br /> natural products, which is essential for activity and represents the greatest<br /> challenge for preparation of these drugs. <o:p></o:p></span></p><br /> <p class=MsoNormal style='margin-bottom:0in;margin-bottom:.0001pt;line-height: normal'><a href="http://www.pnas.org/content/101/16/5788/F1.expansion.html"><span style='font-size:12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family: "Times New Roman";mso-no-proof:yes;text-decoration:none;text-underline:none'><![if !vml]><span style='mso-ignore:vglayout'><img border=0 width=440 height=257 src="Development%20of%20an%20efficien1_files/image001.gif" alt="Fig. 1." v:shapes="Picture_x0020_1"></span><![endif]></span></a><span style='font-size: 12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family:"Times New Roman"'><o:p></o:p></span></p><br /> <p class=MsoNormal style='margin-bottom:0in;margin-bottom:.0001pt;line-height: normal'><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'>View larger version: <o:p></o:p></span></p><br /> <ul type=disc> <li class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal;mso-list:l18 level1 lfo4;tab-stops:list .5in'><span style='font-size:12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family: "Times New Roman"'><a href="http://www.pnas.org/content/101/16/5788/F1.expansion.html" target="_blank">In a new window</a> <o:p></o:p></span></li> </ul><br /> <ul type=disc> <li class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal;mso-list:l0 level1 lfo5;tab-stops:list .5in'><span style='font-size:12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family: "Times New Roman"'><a href="http://www.pnas.org/powerpoint/101/16/5788/F1">Download<br /> as PowerPoint Slide</a><o:p></o:p></span></li> </ul><br /> <p class=MsoNormal style='margin-bottom:0in;margin-bottom:.0001pt;line-height: normal'><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'>Fig. 1. <o:p></o:p></span></p><br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal'><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'>DERA-catalyzed tandem aldol<br /> reaction.<o:p></o:p></span></p><br /> <p class=MsoNormal style='margin-bottom:0in;margin-bottom:.0001pt;line-height: normal'><a href="http://www.pnas.org/content/101/16/5788/F2.expansion.html"><span style='font-size:12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family: "Times New Roman";mso-no-proof:yes;text-decoration:none;text-underline:none'><![if !vml]><span style='mso-ignore:vglayout'><img border=0 width=361 height=440 src="Development%20of%20an%20efficien1_files/image002.gif" alt="Fig. 2." v:shapes="Picture_x0020_2"></span><![endif]></span></a><span style='font-size: 12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family:"Times New Roman"'><o:p></o:p></span></p><br /> <p class=MsoNormal style='margin-bottom:0in;margin-bottom:.0001pt;line-height: normal'><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'>View larger version: <o:p></o:p></span></p><br /> <ul type=disc> <li class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal;mso-list:l7 level1 lfo6;tab-stops:list .5in'><span style='font-size:12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family: "Times New Roman"'><a href="http://www.pnas.org/content/101/16/5788/F2.expansion.html" target="_blank">In a new window</a> <o:p></o:p></span></li> </ul><br /> <ul type=disc> <li class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal;mso-list:l11 level1 lfo7;tab-stops:list .5in'><span style='font-size:12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family: "Times New Roman"'><a href="http://www.pnas.org/powerpoint/101/16/5788/F2">Download<br /> as PowerPoint Slide</a><o:p></o:p></span></li> </ul><br /> <p class=MsoNormal style='margin-bottom:0in;margin-bottom:.0001pt;line-height: normal'><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'>Fig. 2. <o:p></o:p></span></p><br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal'><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'>Structures of Lipitor (atorvastatin)<br /> and Crestor (rosuvastatin).<o:p></o:p></span></p><br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal'><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'>Although the published<br /> DERA-catalyzed reaction offered the potential to greatly simplify the process<br /> for synthesizing the chiral side chain of statins, several issues would limit<br /> its practicability for large-scale production. First, the catalyst load was<br /> very high, ≈200 mg of DERA per gram of isolated product (R<span style='mso-no-proof:yes'><![if !vml]><img border=0 width=19 height=5 src="Development%20of%20an%20efficien1_files/image003.gif" alt=Graphic v:shapes="Picture_x0020_3"><![endif]></span>Cl),<br /> or 20% (wt/wt). Use of such a high concentration of enzyme would make the<br /> process prohibitively expensive, in addition to making isolation of product<br /> from the reaction mixture difficult. Second, the reaction time was on the order<br /> of several days. Third, the concentration of the limiting reagent,<br /> chloroacetaldehyde, was only 100 mM. Taken together, the volumetric<br /> productivity of the published process was 2 g/liter per day. Hence, in this<br /> process, the value of building an advanced statin intermediate, with<br /> establishment of both stereogenic centers from achiral 2-carbon starting<br /> materials in a single reaction, would be offset on process scale by a very<br /> large reaction volume, long reaction time, high catalyst concentration, and<br /> laborious product isolation. In addition to these points, the<br /> enantioselectivity and diastereoselectivity of the DERA-catalyzed reaction was<br /> unknown. <o:p></o:p></span></p><br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal'><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'>We addressed these limitations by (<i>i</i>)<br /> discovering an improved DERA by screening genomic libraries prepared from<br /> environmental DNA and (<i>ii</i>) developing a fed-batch reaction process to<br /> overcome significant substrate inhibition. In addition, an inexpensive<br /> oxidation method has been developed to convert the enzymatic lactol product<br /> into (3<i>R</i>,5<i>S</i>)-6-chloro-2,4,6-trideoxy-<i>erythro</i>-hexonolactone<br /> (<b>1</b>). The crude lactone was determined to have an enantiomeric excess<br /> (ee) of >99.9% and diastereomeric excess (de) of 96.6%. After<br /> crystallization, the lactone had an ee of >99.9% and de of 99.8%. Compound <b>1</b><br /> <br /> was functionalized efficiently to provide side-chain intermediates for<br /> synthesis of a variety of statins. <o:p></o:p></span></p><br /> <p class=MsoNormal style='margin-bottom:0in;margin-bottom:.0001pt;line-height: normal'><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'><a href="http://www.pnas.org/content/101/16/5788.long#abstract-1" title=Abstract>Previous<br /> Section</a><a href="http://www.pnas.org/content/101/16/5788.long#sec-2" title="Results and Discussion">Next Section</a><o:p></o:p></span></p><br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal;mso-outline-level:2'><b><span style='font-size:18.0pt; font-family:"Times New Roman","serif";mso-fareast-font-family:"Times New Roman"'>Materials<br /> and Methods<o:p></o:p></span></b></p><br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal'><b><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'>General.</span></b><span style='font-size:12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family: "Times New Roman"'> All reagents were purchased and used without additional<br /> purification. Reactions were monitored by analytical TLC on silica gel 60 F254<br /> plates and visualized by staining with acidic ceric ammonium molybdate or<br /> potassium permanganate. <sup>1</sup>H and <sup>13</sup>C NMR spectra were<br /> obtained on a Bruker (Billerica, MA) 500-MHz UltraShield spectrometer.<br /> Fed-batch reactions were performed on a Dasgip (Juelich, Germany) Fedbatch-pro<br /> system. GC was performed on an Agilent 6890 gas chromatograph. <o:p></o:p></span></p><br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal'><b><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'>Improved DERA.</span></b><span style='font-size:12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family: "Times New Roman"'> The improved DERA was discovered by high-throughput<br /> screening of environmental DNA libraries, as described in <i>Results and<br /> Discussion</i>. The protein sequence of this aldolase is MNIAKMIDHTLLKPEATEQQIVQLCTEAKQYGFA<br /> AVCVNP TWVKTA AR ELSGTDVRVCTVIGFPLGAT T PETKAFET TNA IENGAR EVDMVINIGA<br /> LKSGQDELVERDIR AVVEA A AGR A LVKVI VETA LLTD EEKVR<br /> ACQLAVKAGADYVKTSTGFSGGGATVEDVA LMRKTVGDR AGVKASGGVRDWKTAEA<br /> MINAGATRIGTSSGVAIVTGGTGRADY. <o:p></o:p></span></p><br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal'><b><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'>Synthesis.</span></b><span style='font-size:12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family: "Times New Roman"'> The synthetic procedures described below are illustrated in<br /> Figs. <a href="http://www.pnas.org/content/101/16/5788.long#F3">3</a>, <a href="http://www.pnas.org/content/101/16/5788.long#F4">4</a>, <a href="http://www.pnas.org/content/101/16/5788.long#F5">5</a>, <a href="http://www.pnas.org/content/101/16/5788.long#F6">6</a>. <o:p></o:p></span></p><br /> <p class=MsoNormal style='margin-bottom:0in;margin-bottom:.0001pt;line-height: normal'><a href="http://www.pnas.org/content/101/16/5788/F3.expansion.html"><span style='font-size:12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family: "Times New Roman";mso-no-proof:yes;text-decoration:none;text-underline:none'><![if !vml]><span style='mso-ignore:vglayout'><img border=0 width=440 height=135 src="Development%20of%20an%20efficien1_files/image004.gif" alt="Fig. 3." v:shapes="Picture_x0020_4"></span><![endif]></span></a><span style='font-size: 12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family:"Times New Roman"'><o:p></o:p></span></p><br /> <p class=MsoNormal style='margin-bottom:0in;margin-bottom:.0001pt;line-height: normal'><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'>View larger version: <o:p></o:p></span></p><br /> <ul type=disc> <li class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal;mso-list:l15 level1 lfo8;tab-stops:list .5in'><span style='font-size:12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family: "Times New Roman"'><a href="http://www.pnas.org/content/101/16/5788/F3.expansion.html" target="_blank">In a new window</a> <o:p></o:p></span></li> </ul><br /> <ul type=disc> <li class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal;mso-list:l17 level1 lfo9;tab-stops:list .5in'><span style='font-size:12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family: "Times New Roman"'><a href="http://www.pnas.org/powerpoint/101/16/5788/F3">Download<br /> as PowerPoint Slide</a><o:p></o:p></span></li> </ul><br /> <p class=MsoNormal style='margin-bottom:0in;margin-bottom:.0001pt;line-height: normal'><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'>Fig. 3. <o:p></o:p></span></p><br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal'><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'>Synthesis of lactone (<b>1</b>).<br /> Reagents and conditions: a, DERA, H<sub>2</sub>O, room temperature, 3 h; b,<br /> NaOCl, HOAc, H<sub>2</sub>O, room temperature, 3 h. <o:p></o:p></span></p><br /> <p class=MsoNormal style='margin-bottom:0in;margin-bottom:.0001pt;line-height: normal'><a href="http://www.pnas.org/content/101/16/5788/F4.expansion.html"><span style='font-size:12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family: "Times New Roman";mso-no-proof:yes;text-decoration:none;text-underline:none'><![if !vml]><span style='mso-ignore:vglayout'><img border=0 width=440 height=211 src="Development%20of%20an%20efficien1_files/image005.gif" alt="Fig. 4." v:shapes="Picture_x0020_5"></span><![endif]></span></a><span style='font-size: 12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family:"Times New Roman"'><o:p></o:p></span></p><br /> <p class=MsoNormal style='margin-bottom:0in;margin-bottom:.0001pt;line-height: normal'><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'>View larger version: <o:p></o:p></span></p><br /> <ul type=disc> <li class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal;mso-list:l1 level1 lfo10;tab-stops:list .5in'><span style='font-size:12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family: "Times New Roman"'><a href="http://www.pnas.org/content/101/16/5788/F4.expansion.html" target="_blank">In a new window</a> <o:p></o:p></span></li> </ul><br /> <ul type=disc> <li class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal;mso-list:l22 level1 lfo11;tab-stops:list .5in'><span style='font-size:12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family: "Times New Roman"'><a href="http://www.pnas.org/powerpoint/101/16/5788/F4">Download<br /> as PowerPoint Slide</a><o:p></o:p></span></li> </ul><br /> <p class=MsoNormal style='margin-bottom:0in;margin-bottom:.0001pt;line-height: normal'><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'>Fig. 4. <o:p></o:p></span></p><br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal'><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'>Reagents and conditions: a, NaCN,<br /> DMF, 5% H<sub>2</sub>O, 40°C, 16 h; b, dimethoxypropane, DMF, catalytic H<sub>2</sub>SO<sub>4</sub>,<br /> then trimethylsilyldiazomethane; c, NaOH, H<sub>2</sub>O, 40°C, 16 h. <o:p></o:p></span></p><br /> <p class=MsoNormal style='margin-bottom:0in;margin-bottom:.0001pt;line-height: normal'><a href="http://www.pnas.org/content/101/16/5788/F5.expansion.html"><span style='font-size:12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family: "Times New Roman";mso-no-proof:yes;text-decoration:none;text-underline:none'><![if !vml]><span style='mso-ignore:vglayout'><img border=0 width=440 height=221 src="Development%20of%20an%20efficien1_files/image006.gif" alt="Fig. 5." v:shapes="Picture_x0020_6"></span><![endif]></span></a><span style='font-size: 12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family:"Times New Roman"'><o:p></o:p></span></p><br /> <p class=MsoNormal style='margin-bottom:0in;margin-bottom:.0001pt;line-height: normal'><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'>View larger version: <o:p></o:p></span></p><br /> <ul type=disc> <li class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal;mso-list:l12 level1 lfo12;tab-stops:list .5in'><span style='font-size:12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family: "Times New Roman"'><a href="http://www.pnas.org/content/101/16/5788/F5.expansion.html" target="_blank">In a new window</a> <o:p></o:p></span></li> </ul><br /> <ul type=disc> <li class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal;mso-list:l9 level1 lfo13;tab-stops:list .5in'><span style='font-size:12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family: "Times New Roman"'><a href="http://www.pnas.org/powerpoint/101/16/5788/F5">Download<br /> as PowerPoint Slide</a><o:p></o:p></span></li> </ul><br /> <p class=MsoNormal style='margin-bottom:0in;margin-bottom:.0001pt;line-height: normal'><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'>Fig. 5. <o:p></o:p></span></p><br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal'><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'>Preparation of chiral standards for<br /> analysis of <b>1</b>. Reagents and conditions: a, NaBH<sub>4</sub>, MeOH; b,<br /> 15% trifluoroacetic acid, CH<sub>2</sub>Cl<sub>2</sub>, 1% triethylsilane. <o:p></o:p></span></p><br /> <p class=MsoNormal style='margin-bottom:0in;margin-bottom:.0001pt;line-height: normal'><a href="http://www.pnas.org/content/101/16/5788/F6.expansion.html"><span style='font-size:12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family: "Times New Roman";mso-no-proof:yes;text-decoration:none;text-underline:none'><![if !vml]><span style='mso-ignore:vglayout'><img border=0 width=440 height=324 src="Development%20of%20an%20efficien1_files/image007.gif" alt="Fig. 6." v:shapes="Picture_x0020_7"></span><![endif]></span></a><span style='font-size: 12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family:"Times New Roman"'><o:p></o:p></span></p><br /> <p class=MsoNormal style='margin-bottom:0in;margin-bottom:.0001pt;line-height: normal'><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'>View larger version: <o:p></o:p></span></p><br /> <ul type=disc> <li class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal;mso-list:l13 level1 lfo14;tab-stops:list .5in'><span style='font-size:12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family: "Times New Roman"'><a href="http://www.pnas.org/content/101/16/5788/F6.expansion.html" target="_blank">In a new window</a> <o:p></o:p></span></li> </ul><br /> <ul type=disc> <li class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal;mso-list:l10 level1 lfo15;tab-stops:list .5in'><span style='font-size:12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family: "Times New Roman"'><a href="http://www.pnas.org/powerpoint/101/16/5788/F6">Download<br /> as PowerPoint Slide</a><o:p></o:p></span></li> </ul><br /> <p class=MsoNormal style='margin-bottom:0in;margin-bottom:.0001pt;line-height: normal'><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'>Fig. 6. <o:p></o:p></span></p><br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal'><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'>Synthesis and retro-aldol reaction<br /> of fluorogenic DERA substrate. a, 4-methylumbelliferone, K<sub>2</sub>CO<sub>3</sub>,<br /> DMF, 75°C, 16 h; b, H<sub>2</sub>O/20% CH<sub>3</sub>CN, Dowex 50WX8-100, 2<br /> days. <o:p></o:p></span></p><br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal'><b><i><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'>(3R,5S)-6-Chloro-2,4,6-trideoxy-erythro-hexose<br /> (2).</span></i></b><b><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'> </span></b><span style='font-size: 12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family:"Times New Roman"'>Lyophilized<br /> crude DERA lysate (1.3 g of powder, 220 mg of pure DERA) was dissolved in 70 ml<br /> of water. An aqueous solution containing 1.5 M chloroacetaldehyde and 3.1 M<br /> acetaldehyde was fed into the stirred enzyme solution at a rate of 16.66 ml/h<br /> for 3 h, resulting in a final volume of 120 ml. Acetone (200 ml) was added to<br /> precipitate protein, and the mixture was filtered through Celite. The filtrate<br /> was concentrated under reduced pressure to a volume of 50 ml and extracted<br /> three times with 75 ml of ethyl acetate. The organic fraction was dried over<br /> anhydrous sodium sulfate and concentrated under reduced pressure to provide<br /> crude lactol (11.12 g) as a light-yellow oil. The crude product was carried on<br /> to the oxidation step without additional purification. <o:p></o:p></span></p><br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal'><b><i><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'>(3R,5S)-6-Chloro-2,4,6-trideoxy-erythro-hexonolactone<br /> (1).</span></i></b><b><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'> </span></b><span style='font-size: 12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family:"Times New Roman"'>Crude<br /> lactol (<b>2</b>) (75.0 g, ≈0.45 mol) was dissolved in glacial acetic<br /> acid (600 ml). Aqueous sodium hypochlorite (265 ml of a 13% solution) was added<br /> dropwise to the solution over 3 h. The reaction mixture was concentrated under<br /> reduced pressure to a volume of 200 ml, neutralized by addition of solid sodium<br /> bicarbonate, and extracted twice with 500 ml of ethyl acetate. The organic fraction<br /> was dried over sodium sulfate, concentrated to dryness under reduced pressure,<br /> and dissolved in 350 ml of chloroform. The solution was cooled slowly to –20°C,<br /> and after 12 h, crystalline product was collected, washed with cold chloroform,<br /> and dried under vacuum. Lactone <b>1</b> was obtained as white crystals (44.0<br /> g, 0.267 mol, 45% over two steps): <sup>1</sup>H NMR (500 MHz) CDCl<sub>3</sub><br /> δ 5.01 (1H, m), 4.47 (1H, m), 3.80 (1H, m), 3.68 (1H, m), 2.69 (2H, d, <i>J</i><br /> <br /> = 3.6 Hz), 2.09 (1H, m), 1.97 (1H, m). <sup>13</sup>C NMR (125 MHz) CDCl<sub>3</sub><br /> δ 170.15, 74.81, 62.50, 46.55, 38.54, 32.77. <o:p></o:p></span></p><br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal'><b><i><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'>(4R,6R)-[6-Cyanomethyl-2,2-dimethyl(1,3)dioxan-4-yl]acetic<br /> acid methyl ester (3).</span></i></b><b><span style='font-size:12.0pt; font-family:"Times New Roman","serif";mso-fareast-font-family:"Times New Roman"'><br /> </span></b><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'>Lactone <b>1</b> (10.0 g, 60.7 mmol)<br /> was dissolved in 200 ml of dimethylformamide (DMF). Sodium cyanide (8.93 g, 182<br /> mmol) was dissolved in 10 ml of water. The aqueous cyanide solution was added<br /> to the DMF solution of chlorolactone. The mixture was stirred at 40°C for 16 h.<br /> At the 4-h time point, NMR analysis indicated the presence of chloro diol<br /> carboxylate, an epoxide intermediate, and cyano diol carboxylate. After 16 h,<br /> the nitrile was the major product. The crude product mixture was partially<br /> concentrated under reduced pressure to remove the water (to a final volume of<br /> ≈100 ml). It then was acidified carefully to pH ≈ 3 with<br /> concentrated sulfuric acid (≈3 ml) and purged for 1 h with nitrogen gas.<br /> Dimethoxypropane (21.2 g, 203.3 mmol) was added, and the mixture was stirred at<br /> room temperature for 2 h. The solution then was titrated with<br /> trimethylsilyldiazomethane (2 M solution in hexane) until bubbling was no<br /> longer observed and the final pH was ≈7. Excess<br /> trimethylsilyldiazomethane was quenched with 0.1 ml of acetic acid. Water (200<br /> ml) was added, and the product was extracted with 200 ml of ethyl acetate. The<br /> organic layer was back-extracted with 100 ml of water and then dried over<br /> sodium sulfate and concentrated under reduced pressure. The residue was<br /> purified on silica, eluting with 4:1 hexane/ethyl acetate, yielding 6.52 g of<br /> light-yellow oil (48% over 3 steps from chlorolactone <b>1</b>). Epoxide<br /> intermediate: <sup>1</sup>H NMR (sodium salt) (500 MHz) <sup>2</sup>H<sub>2</sub>O<br /> <br /> δ 3.87 (1H, m), 2.88 (1H, m), 2.58 (1H, app. t, <i>J</i> = 4.2 Hz), 2.34<br /> (1H, dd, <i>J</i> <sub>1</sub> = 3.1 Hz, <i>J</i> <sub>2</sub> = 2.8 Hz), 2.09<br /> (2H, d, <i>J</i> = 6.7 Hz), 1.47 (1H, dt, <i>J</i> <sub>1</sub> = 9.5 Hz, <i>J</i><br /> <br /> <sub>2</sub> = 5.0 Hz), 1.39 (1H, m). Compound <b>3</b>: <sup>1</sup>H NMR (500<br /> MHz) CDCl<sub>3</sub> δ 4.35 (1H, m), 4.17 (1H, m), 3.70 (3H, s), 2.59<br /> (1H, dd, <i>J</i> <sub>1</sub> = 15.8 Hz, <i>J</i> <sub>2</sub> = 6.9 Hz), 2.51<br /> (2H, m), 2.43 (1H, dd, <i>J</i> <sub>1</sub> = 15.8 Hz, <i>J</i> <sub>2</sub> =<br /> 6.1 Hz), 1.78 (1H, dt, <i>J</i> <sub>1</sub> = 12.6 Hz, <i>J</i> <sub>2</sub> =<br /> 2.5 Hz), 1.48 (3H, s), 1.39 (3H, s), 1.33 (1H, dd, <i>J</i> <sub>1</sub> = 18.3<br /> Hz, <i>J</i> <sub>2</sub> = 11.6 Hz); <sup>13</sup>C NMR (125 MHz) CDCl<sub>3</sub><br /> <br /> δ 171.22, 116.92, 99.76, 65.56, 65.16, 51.97, 41.04, 35.58, 29.90, 25.12,<br /> 19.79. <o:p></o:p></span></p><br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal'><b><i><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'>(3R,5S)-3,5,6-Trihydroxyhexanoic<br /> acid (4).</span></i></b><b><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'> </span></b><span style='font-size: 12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family:"Times New Roman"'>Lactone<br /> 1 (330 mg, 2 mmol) was dissolved in 5 ml of water. Sodium hydroxide (176 mg,<br /> 4.4 mmol) was added, and the mixture was stirred at 40°C for 16 h. The solvent<br /> was removed under reduced pressure to provide a white solid, which was<br /> dissolved in <sup>2</sup>H<sub>2</sub>O for NMR analysis: <sup>1</sup>H NMR<br /> (sodium salt) (500 MHz) <sup>2</sup>H<sub>2</sub>O δ 4.08 (1H, m), 3.79<br /> (1H, m), 3.50 (1H, m), 3.41 (1H, m), 2.31 (2H, m), 1.52 (1H, m), 1.48 (1H, m); <sup>13</sup>C<br /> NMR (125 MHz) <sup>2</sup>H<sub>2</sub>O δ 179.93, 70.41, 67.92, 67.19,<br /> 45.80, 41.52. <o:p></o:p></span></p><br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal'><b><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'>Chiral Analysis.</span></b><span style='font-size:12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family: "Times New Roman"'> Enantio- and diastereoselectivity of crude and<br /> recrystallized lactone <b>1</b> were determined by chiral GC using β-Dex<br /> 225 + β-Dex 120 columns in series. A representative GC trace is shown in <a href="http://www.pnas.org/content/101/16/5788.long#F7">Fig. 7</a>. A mixture of<br /> all four possible diastereomers was prepared as illustrated in <a href="http://www.pnas.org/content/101/16/5788.long#F5">Fig. 5</a> and described<br /> below. <o:p></o:p></span></p><br /> <p class=MsoNormal style='margin-bottom:0in;margin-bottom:.0001pt;line-height: normal'><a href="http://www.pnas.org/content/101/16/5788/F7.expansion.html"><span style='font-size:12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family: "Times New Roman";mso-no-proof:yes;text-decoration:none;text-underline:none'><![if !vml]><span style='mso-ignore:vglayout'><img border=0 width=440 height=212 src="Development%20of%20an%20efficien1_files/image008.gif" alt="Fig. 7." v:shapes="Picture_x0020_8"></span><![endif]></span></a><span style='font-size: 12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family:"Times New Roman"'><o:p></o:p></span></p><br /> <p class=MsoNormal style='margin-bottom:0in;margin-bottom:.0001pt;line-height: normal'><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'>View larger version: <o:p></o:p></span></p><br /> <ul type=disc> <li class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal;mso-list:l4 level1 lfo16;tab-stops:list .5in'><span style='font-size:12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family: "Times New Roman"'><a href="http://www.pnas.org/content/101/16/5788/F7.expansion.html" target="_blank">In a new window</a> <o:p></o:p></span></li> </ul><br /> <ul type=disc> <li class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal;mso-list:l16 level1 lfo17;tab-stops:list .5in'><span style='font-size:12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family: "Times New Roman"'><a href="http://www.pnas.org/powerpoint/101/16/5788/F7">Download<br /> as PowerPoint Slide</a><o:p></o:p></span></li> </ul><br /> <p class=MsoNormal style='margin-bottom:0in;margin-bottom:.0001pt;line-height: normal'><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'>Fig. 7. <o:p></o:p></span></p><br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal'><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'>GC conditions: columns, β-Dex<br /> 225 (30 m × 0.25 mm × 0.25 μm) plus β-Dex 120 (30 m × 0.25 mm × 0.25<br /> μm); oven temperature, 180°C; carrier gas He flow rate, 1.0 ml/min. (<i>A</i>)<br /> Chromatogram of lactone <b>1</b> standard with an approximate ratio of (3<i>R</i>,5<i>S</i>)/(3<i>S</i>,5<i>R</i>)/(3<i>R</i>,5<i>R</i>)/(3<i>S</i>,5<i>S</i>)<br /> = 1:1:3:3. (<i>B</i>) Chromatogram of actual sample from the chemoenzymatic<br /> process with an analysis result of >99.94% ee and 96.60% de using the<br /> indicated GC method. Peak 1, (3<i>R</i>,5<i>R</i>) or (3<i>S</i>,5<i>S</i>)<br /> stereoisomer; peak 2, (3<i>R</i>,5<i>R</i>) or (3<i>S</i>,5<i>S</i>)<br /> stereoisomer; peak 3, (3<i>S</i>,5<i>R</i>) stereoisomer; peak 4, (3<i>R</i>,5<i>S</i>)<br /> stereoisomer. <o:p></o:p></span></p><br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal'><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'>6-Chloro-3,5-dioxohexanoic acid<br /> tert-butyl ester (<a href="http://www.pnas.org/content/101/16/5788.long#ref-16">16</a>)<br /> (2.0 g, 8.5 mmol) was dissolved in 40 ml of methanol at 0°C. Sodium borohydride<br /> (750 mg, 20 mmol) was added, and the mixture was stirred for 30 min at 0°C. The<br /> solvent was removed under reduced pressure, and the residue was extracted<br /> between 75 ml of ethyl acetate and 50 ml of water. The organic layer was dried<br /> over anhydrous sodium sulfate and concentrated under reduced pressure. The<br /> crude diol product (300 mg) was dissolved in 5 ml of 15% trifluoroacetic acid<br /> in dichloromethane with 1% triethylsilane. The mixture was stirred at room<br /> temperature for 1.5 h and then concentrated under reduced pressure. The residue<br /> was extracted between 30 ml of ethyl acetate and 30 ml of concentrated aqueous<br /> sodium bicarbonate. The organic layer was dried over sodium sulfate, concentrated,<br /> and purified by silica gel chromatography, eluting with 3:1 ethyl<br /> acetate/hexane, with partial separation of diastereomeric pairs of lactones.<br /> Fraction A consisted of 52 mg of a 1:1 mixture, and fraction B consisted of 27<br /> mg of a 1:3 mixture in favor of the 3<i>R</i>,5<i>R</i>/3<i>S</i>,5<i>S</i><br /> pair. Spectral data for the 3<i>R</i>,5<i>S</i>/3<i>S</i>,5<i>R</i> racemic<br /> mixture: <sup>1</sup>H NMR (500 MHz) CDCl<sub>3</sub> δ 5.01 (1H, m), 4.47<br /> (1H, m), 3.80 (1H, m), 3.68 (1H, m), 2.69 (2H, d, <i>J</i> = 3.6 Hz), 2.09 (1H,<br /> m), 1.97 (1H, m); <sup>13</sup>C NMR (125 MHz) CDCl<sub>3</sub> δ 170.15,<br /> 74.81, 62.50, 46.55, 38.54, 32.77. Spectral data for the 3<i>S</i>,5<i>S</i>/3<i>R</i>,5<i>R</i><br /> <br /> racemic mixture: <sup>1</sup>H NMR (500 MHz) CDCl<sub>3</sub> δ 4.50 (1H,<br /> m), 4.32 (1H, m), 3.72 (2H, dd, <i>J</i> <sub>1</sub> = 5.1 Hz, <i>J</i> <sub>2</sub><br /> = 1.1 Hz), 2.92(1H, m), 2.53 (1H, m), 2.39 (1H, m), 1.83 (1H, m); <sup>13</sup>C<br /> NMR (125 MHz) CDCl<sub>3</sub> δ 170.01, 76.24, 63.47, 45.81, 39.49,<br /> 34.95. <o:p></o:p></span></p><br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal'><b><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'>Fluorogenic DERA Substrate.</span></b><span style='font-size:12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family: "Times New Roman"'> The substrate was prepared from known methyl<br /> 5-toluenesulfonyl-2-deoxyriboside (<a href="http://www.pnas.org/content/101/16/5788.long#ref-17">17</a>). The<br /> toluenesulfonate (12.75 g, 42.2 mmol) was dissolved in 75 ml of DMF. To the<br /> solution was added potassium carbonate (11.68 g, 84.5 mmol) and<br /> 4-methylumbelliferone (9.29 g, 52.8 mmol). The mixture was stirred at 75°C for<br /> 16 h. Water (300 ml) was added, and the mixture was extracted twice with 200 ml<br /> of ethyl acetate. The organic layer was back-extracted with 100 ml of 0.1 M<br /> aqueous sodium hydroxide, dried over sodium sulfate, and concentrated. The<br /> crude product (9.05 g) was dissolved in 25 ml of acetonitrile and 100 ml of<br /> water. Dowex 50WX8-100 (2.5 g) was added, and the mixture was stirred at room<br /> temperature. After 1.5 h, the mixture was exposed to reduced pressure to remove<br /> methanol and then returned to atmospheric pressure. After 2 days, the mixture was<br /> filtered, concentrated under reduced pressure, and purified by silica gel<br /> chromatography, eluting with a gradient from 100% ethyl acetate to 10%<br /> acetone/ethyl acetate. The product was obtained as a white foam (5.31 g, 62%)<br /> as a 1:1 mixture of anomers: <sup>1</sup>H NMR (500 MHz) DMSO-d<sub>6</sub><br /> δ 7.70 (1H, m), 6.97 (2H, m), 6.32 (1H, m, 1α), 6.20 (1H, m,<br /> 1β), 6.19 (1H, m), 5.40 (1H, br), 5.17 (1H, br), 4.0–4.3 (4H, m), 2.38<br /> (3H, s), 1.65–2.0 (2H, m); <sup>13</sup>C NMR (125 MHz) CDCl<sub>3</sub> δ<br /> <br /> 161.63, 160.12, 154.68, 153.35, 126.43, 113.18, 112.38, 111.17, 101.28, 97.86,<br /> 97.05, 82.93, 80.89, 70.93, 70.69, 70.56, 68.94, 42.11, 18.09. <o:p></o:p></span></p><br /> <p class=MsoNormal style='margin-bottom:0in;margin-bottom:.0001pt;line-height: normal'><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'><a href="http://www.pnas.org/content/101/16/5788.long#sec-1" title="Materials and Methods">Previous Section</a><a href="http://www.pnas.org/content/101/16/5788.long#sec-3" title=Conclusions>Next<br /> Section</a><o:p></o:p></span></p><br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal;mso-outline-level:2'><b><span style='font-size:18.0pt; font-family:"Times New Roman","serif";mso-fareast-font-family:"Times New Roman"'>Results<br /> and Discussion<o:p></o:p></span></b></p><br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal'><b><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'>Discovery of an Improved DERA.</span></b><span style='font-size:12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family: "Times New Roman"'> To improve the commercial viability of the process, we<br /> sought to discover and develop a DERA that was improved over the enzyme from <i>Escherichia<br /> coli</i> in two specific parameters: tolerance to high substrate concentrations<br /> and reduced catalyst load. Thus, we desired an enzyme that would produce more<br /> product per liter while at the same time using less enzyme than would be<br /> required with <i>E. coli</i> DERA. In an effort to access the most diverse<br /> range of enzymes that occur in nature, we create large genomic libraries by<br /> extracting DNA directly from environmental samples collected around the world<br /> from a variety of habitats (<a href="http://www.pnas.org/content/101/16/5788.long#ref-18">18</a>). These<br /> environmental genomic libraries are screened through a variety of<br /> high-throughput methods including both fluorogenic activity-based screens and<br /> sequence-based screens (<a href="http://www.pnas.org/content/101/16/5788.long#ref-19">19</a>). Our<br /> fluorescent DERA assay, based on technology developed by Reymond and coworkers<br /> (<a href="http://www.pnas.org/content/101/16/5788.long#ref-20">20</a>), uses a<br /> fluorogenic substrate analog that undergoes a retro-aldol reaction in the<br /> presence of a DERA (<a href="http://www.pnas.org/content/101/16/5788.long#F6">Fig.<br /> 6</a>). The resultant fragment spontaneously eliminates to produce fluorescent<br /> 4-methylumbelliferone. Using these methods, we discovered >15 DERAs that<br /> exhibited activity in the title reaction. All these enzymes were overexpressed<br /> and compared directly to the <i>E. coli</i> DERA in the commercially relevant<br /> reaction (<a href="http://www.pnas.org/content/101/16/5788.long#F1">Fig. 1</a>).<br /> One enzyme was found to be superior, and results for this DERA are described in<br /> the following section. Because it was discovered from large, mixed genomic<br /> libraries created from environmental DNA, the source organism for the improved<br /> DERA is unknown. The protein sequence has <30% identity to <i>E. coli</i><br /> <br /> DERA and has closest homology to putative DERAs from Gram-positive organisms. <o:p></o:p></span></p><br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal'><b><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'>Aldolase Reaction.</span></b><span style='font-size:12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family: "Times New Roman"'> As noted previously, the reported volumetric productivity<br /> levels observed for the reaction between acetaldehyde and chloroacetaldehyde<br /> using <i>E. coli</i> DERA were exceedingly low (2 g/liter per day). To address<br /> this point, we further investigated the cause for limited volumetric<br /> productivity as well as the high catalyst load requirement in this<br /> transformation. Both the <i>E. coli</i> enzyme and our DERA were examined for<br /> inhibition, and no effect was observed when acetaldehyde concentration was<br /> increased when holding chloroacetaldehyde concentration constant. By contrast,<br /> when attempts were made to increase the chloroacetaldehyde concentration, the<br /> reaction was halted completely. Inhibition by chloroacetaldehyde, a potent<br /> electrophile, was overcome by process improvements that entailed slow feeding<br /> of the substrates over 3 h, at a constant ratio of 2:1<br /> acetaldehyde/chloroacetaldehyde, into the reaction at a rate such that they<br /> were consumed as fast as they were added. Thus, chloroacetaldehyde did not<br /> reach inhibitory concentrations, and the reaction proceeded to completion. The<br /> improved DERA was expressed on a scale of hundreds of grams, and directly<br /> compared (with respect to catalyst load and volumetric productivity) with the <i>E.<br /> coli</i> enzyme under the same substrate feeding conditions. <o:p></o:p></span></p><br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal'><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'>We examined lactol productivity<br /> levels that could be achieved under the improved process conditions. The <i>E.<br /> coli</i> DERA performed significantly better, producing a maximum of 76 g/liter<br /> (456 mM) product over 3 h, with a minimum catalyst load of 4.8% (wt/wt). When<br /> lower concentrations of <i>E. coli</i> DERA were used, much lower product<br /> yields were achieved. Even greater performance was observed with our improved<br /> DERA, which reached 93 g/liter (558 mM) product over 3 h, with a catalyst load<br /> of only 2.0% (wt/wt). By discovering a DERA with improved activity and<br /> substrate tolerance and converting from a batch reaction to a fed-batch<br /> process, we were able to reach ≈7-fold higher product concentrations<br /> (>0.5 M) while at the same time using less enzyme (<2 g DERA per liter,<br /> or ≈75 μM), compared with the published process. Tolerance to even<br /> higher aldehyde concentrations may be engineered into the aldolase by directed<br /> evolution. Thus, higher concentrations of product could be achieved in the same<br /> time while expending less than half as much enzyme, rendering the process<br /> significantly more cost-effective. <o:p></o:p></span></p><br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal'><b><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'>Oxidation to Lactone (</span></b><span style='font-size:12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family: "Times New Roman"'> <a href="http://www.pnas.org/content/101/16/5788.long#ref-1"><b>1</b><br /> <br /> </a><b>).</b> The published procedure for oxidation of the enzymatic lactol<br /> product to the lactone entailed reaction with bromine and barium carbonate (<a href="http://www.pnas.org/content/101/16/5788.long#ref-14">14</a>, <a href="http://www.pnas.org/content/101/16/5788.long#ref-21">21</a>). Although<br /> this process was effective on a laboratory scale, the expense and toxicity of<br /> bromine would prohibit its use in a large-scale process. We identified a very<br /> inexpensive method for the selective oxidation to lactone <b>1</b> by using<br /> aqueous sodium hypochlorite and acetic acid. Lactone <b>1</b> is crystalline,<br /> providing a readily scalable method for purification by recrystallization. This<br /> process yielded a product of exceptional enantiomeric and diastereomeric<br /> purity, as described in the following section. <o:p></o:p></span></p><br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal'><b><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'>Enantio- and Diastereoselectivity.</span></b><span style='font-size:12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family: "Times New Roman"'> Because the enzymatic product <b>2</b> exists as an<br /> equilibrium mixture of α and β anomers, chiral analysis of the<br /> enzymatic reaction was performed after oxidation to compound <b>1</b> to<br /> simplify the process. Because two stereogenic centers are set in a single pot,<br /> four isomers (two enantiomeric pairs of diastereomers) can be formed. Relative<br /> to the desired (3<i>R</i>,5<i>S</i>) product, improper setting of the first, or<br /> second, center leads to the diastereomeric (3<i>R</i>,5<i>R</i>) and (3<i>S</i>,5<i>S</i>)<br /> isomers, respectively. Improper setting of both centers leads to the<br /> enantiomeric (3<i>S</i>,5<i>R</i>) isomer, as illustrated in <a href="http://www.pnas.org/content/101/16/5788.long#F8">Fig. 8</a>. Because both<br /> centers are set in the same reaction, exquisite enantioselectivity is observed.<br /> Each of the two individual centers is set with 98–99% ee, thus the likelihood<br /> that the undesired stereochemistry is formed at both centers on the same<br /> molecule is vanishingly small. For instance, if the first center is set<br /> improperly, it is most likely that the second center will be set properly,<br /> leading to the diastereomeric (3<i>S</i>,5<i>S</i>) product. The two<br /> diastereomeric products were observed as a combined 1.7% of the total crude<br /> lactone concentration, and the enantiomeric (3<i>S</i>,5<i>R</i>) isomer was<br /> observed in <0.05%, giving a de of 96.6% and ee of >99.9%. The<br /> diastereomeric impurities were separated effectively from the desired product<br /> by recrystallization, providing <b>1</b> with an ee of >99.9% and de of<br /> 99.8%. Diastereoselectivity may be improved further by performing directed<br /> evolution on the aldolase. <o:p></o:p></span></p><br /> <p class=MsoNormal style='margin-bottom:0in;margin-bottom:.0001pt;line-height: normal'><a href="http://www.pnas.org/content/101/16/5788/F8.expansion.html"><span style='font-size:12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family: "Times New Roman";mso-no-proof:yes;text-decoration:none;text-underline:none'><![if !vml]><span style='mso-ignore:vglayout'><img border=0 width=440 height=272 src="Development%20of%20an%20efficien1_files/image009.gif" alt="Fig. 8." v:shapes="Picture_x0020_9"></span><![endif]></span></a><span style='font-size: 12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family:"Times New Roman"'><o:p></o:p></span></p><br /> <p class=MsoNormal style='margin-bottom:0in;margin-bottom:.0001pt;line-height: normal'><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'>View larger version: <o:p></o:p></span></p><br /> <ul type=disc> <li class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal;mso-list:l19 level1 lfo18;tab-stops:list .5in'><span style='font-size:12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family: "Times New Roman"'><a href="http://www.pnas.org/content/101/16/5788/F8.expansion.html" target="_blank">In a new window</a> <o:p></o:p></span></li> </ul><br /> <ul type=disc> <li class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal;mso-list:l20 level1 lfo19;tab-stops:list .5in'><span style='font-size:12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family: "Times New Roman"'><a href="http://www.pnas.org/powerpoint/101/16/5788/F8">Download<br /> as PowerPoint Slide</a><o:p></o:p></span></li> </ul><br /> <p class=MsoNormal style='margin-bottom:0in;margin-bottom:.0001pt;line-height: normal'><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'>Fig. 8. <o:p></o:p></span></p><br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal'><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'>Enantio- and diastereoselectivity of<br /> the DERA-catalyzed process.<o:p></o:p></span></p><br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal'><b><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'>Conversion of 1 to Statin<br /> Intermediates.</span></b><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'> Although the DERA-catalyzed process<br /> economically provided highly pure <b>1</b> in only two steps, it remained to<br /> convert this compound to desired statin intermediates by converting the<br /> chloride to the relevant functionality (e.g., a nitrile for atorvastatin and<br /> hydroxyl group for rosuvastatin). This process entailed opening the lactone<br /> ring of <b>1</b> with appropriate nucleophiles and introducing suitable protecting<br /> groups. For example, triol acid <b>4</b> was formed cleanly and quantitatively<br /> after treatment of lactone <b>1</b> with aqueous NaOH at 45°C over 16 h (<a href="http://www.pnas.org/content/101/16/5788.long#F4">Fig. 4</a>).<br /> Furthermore, when <b>1</b> was stirred at 45°C in wet DMF with 3 eq of NaCN (<a href="http://www.pnas.org/content/101/16/5788.long#F9">Fig. 9</a>), the lactone<br /> was hydrolyzed within minutes to the chloro diol intermediate <b>5</b>. This<br /> intermediate was consumed over several hours, and epoxide intermediate <b>6</b><br /> <br /> concomitantly increased in concentration, as revealed by <sup>1</sup>H and <sup>13</sup>C<br /> NMR spectroscopy. The epoxide subsequently was opened regioselectively by<br /> cyanide, with complete conversion in 16 h. At the 4-h time point, the chloro<br /> diol, epoxide, and cyano diol were present in approximately equimolar<br /> quantities. It should be noted that epoxide <b>6</b> also was observed as an<br /> intermediate during the basic hydrolysis of lactone <b>1</b> to afford the<br /> triol acid <b>4</b>. <o:p></o:p></span></p><br /> <p class=MsoNormal style='margin-bottom:0in;margin-bottom:.0001pt;line-height: normal'><a href="http://www.pnas.org/content/101/16/5788/F9.expansion.html"><span style='font-size:12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family: "Times New Roman";mso-no-proof:yes;text-decoration:none;text-underline:none'><![if !vml]><span style='mso-ignore:vglayout'><img border=0 width=440 height=225 src="Development%20of%20an%20efficien1_files/image010.gif" alt="Fig. 9." v:shapes="Picture_x0020_10"></span><![endif]></span></a><span style='font-size: 12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family:"Times New Roman"'><o:p></o:p></span></p><br /> <p class=MsoNormal style='margin-bottom:0in;margin-bottom:.0001pt;line-height: normal'><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'>View larger version: <o:p></o:p></span></p><br /> <ul type=disc> <li class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal;mso-list:l6 level1 lfo20;tab-stops:list .5in'><span style='font-size:12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family: "Times New Roman"'><a href="http://www.pnas.org/content/101/16/5788/F9.expansion.html" target="_blank">In a new window</a> <o:p></o:p></span></li> </ul><br /> <ul type=disc> <li class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal;mso-list:l21 level1 lfo21;tab-stops:list .5in'><span style='font-size:12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family: "Times New Roman"'><a href="http://www.pnas.org/powerpoint/101/16/5788/F9">Download<br /> as PowerPoint Slide</a><o:p></o:p></span></li> </ul><br /> <p class=MsoNormal style='margin-bottom:0in;margin-bottom:.0001pt;line-height: normal'><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'>Fig. 9. <o:p></o:p></span></p><br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal'><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'>Cyanide displacement through an<br /> epoxide intermediate.<o:p></o:p></span></p><br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal'><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'>Protection of the cyano diol <b>7</b><br /> in a two-step, single-pot process provided intermediate <b>3</b> in 48% overall<br /> yield from <b>1</b>. It should be noted that these are preliminary results, and<br /> there is potential for additional optimization of the chemical steps that follow<br /> the DERA-catalyzed process. Likewise, it should be possible to further improve<br /> the enzyme's specific activity and tolerance of high aldehyde concentrations in<br /> the DERA process by directed evolution (<a href="http://www.pnas.org/content/101/16/5788.long#ref-8">8</a>). The complete<br /> process to the protected, fully elaborated, enantiomerically pure atorvastatin<br /> side chain intermediate <b>3</b> entailed only five steps from<br /> chloroacetaldehyde and acetaldehyde. <o:p></o:p></span></p><br /> <p class=MsoNormal style='margin-bottom:0in;margin-bottom:.0001pt;line-height: normal'><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'><a href="http://www.pnas.org/content/101/16/5788.long#sec-2" title="Results and Discussion">Previous Section</a><a href="http://www.pnas.org/content/101/16/5788.long#ack-1" title=Acknowledgments>Next Section</a><o:p></o:p></span></p><br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal;mso-outline-level:2'><b><span style='font-size:18.0pt; font-family:"Times New Roman","serif";mso-fareast-font-family:"Times New Roman"'>Conclusions<o:p></o:p></span></b></p><br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal'><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'>By a combination of discovery of<br /> superior DERAs from environmental DNA libraries and process improvements to<br /> overcome substrate inhibition, we developed a highly efficient, cost-effective,<br /> scalable, and enantioselective biocatalytic process. The aldolase-catalyzed<br /> step proceeded with an ee of >99.9% and de of 96.6%. After oxidation,<br /> crystalline lactone <b>1</b> was obtained with an ee of >99.9% and de of<br /> 99.8%. The volumetric productivity of the enzymatic process, which has been<br /> performed on a 100-g scale, was improved to 30.6 g/liter per h (from 0.08<br /> g/liter per h for a published process). Downstream chemical transformations<br /> have been developed to convert the enzymatic product to key statin<br /> intermediates. The complete process, integrating a key biocatalytic step<br /> forming two carbon–carbon bonds stereoselectively with subsequent chemical<br /> transformations, represents a general, practical, and economical route to<br /> statins. <o:p></o:p></span></p><br /> <p class=MsoNormal style='margin-bottom:0in;margin-bottom:.0001pt;line-height: normal'><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'><a href="http://www.pnas.org/content/101/16/5788.long#sec-3" title=Conclusions>Previous<br /> Section</a><a href="http://www.pnas.org/content/101/16/5788.long#fn-group-1" title=Footnotes>Next Section</a><o:p></o:p></span></p><br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal;mso-outline-level:2'><b><span style='font-size:18.0pt; font-family:"Times New Roman","serif";mso-fareast-font-family:"Times New Roman"'>Acknowledgments<o:p></o:p></span></b></p><br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal'><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'>We thank C. Abulencia, D. Wyborski,<br /> A. Milan, and M. Miller for enzyme discovery; J. Verruto and X. Tan for<br /> subcloning; T. Kaneko and J. Patel for fermentation; T. Richardson and M. Podar<br /> for bioinformatics support; and J. Gemsch and L. Bibbs for sequencing. <o:p></o:p></span></p><br /> <p class=MsoNormal style='margin-bottom:0in;margin-bottom:.0001pt;line-height: normal'><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'><a href="http://www.pnas.org/content/101/16/5788.long#ack-1" title=Acknowledgments>Previous Section</a><a href="http://www.pnas.org/content/101/16/5788.long#ref-list-1" title=References>Next Section</a><o:p></o:p></span></p><br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal;mso-outline-level:2'><b><span style='font-size:18.0pt; font-family:"Times New Roman","serif";mso-fareast-font-family:"Times New Roman"'>Footnotes<o:p></o:p></span></b></p><br /> <ul type=disc> <li class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal;mso-list:l14 level1 lfo22;tab-stops:list .5in'><span style='font-size:12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family: "Times New Roman"'><a href="http://www.pnas.org/content/101/16/5788.long#xref-fn-1-1"><span style='font-family:"Cambria Math","serif";mso-bidi-font-family:"Cambria Math"'>↵</span></a><br /> <br /> * To whom correspondence may be addressed. E-mail: <a href="mailto:wgreenberg@diversa.com">wgreenberg@diversa.com</a> or <a href="mailto:mburk@diversa.com">mburk@diversa.com</a>. <o:p></o:p></span></li> <li class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal;mso-list:l14 level1 lfo22;tab-stops:list .5in'><span style='font-size:12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family: "Times New Roman"'>This paper was submitted directly (Track II) to the<br /> PNAS office.<o:p></o:p></span></li> <li class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal;mso-list:l14 level1 lfo22;tab-stops:list .5in'><span style='font-size:12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family: "Times New Roman"'>Abbreviations: DERA, deoxyribose-5-phosphate aldolase;<br /> ee, enantiomeric excess; de, diastereomeric excess; DMF,<br /> dimethylformamide.<o:p></o:p></span></li> <li class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:normal;mso-list:l14 level1 lfo22;tab-stops:list .5in'><span style='font-size:12.0pt;font-family:"Times New Roman","serif";mso-fareast-font-family: "Times New Roman"'>Copyright © 2004, The National Academy of Sciences<o:p></o:p></span></li> </ul><br /> <p class=MsoNormal style='margin-bottom:0in;margin-bottom:.0001pt;line-height: normal'><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'><a href="http://www.pnas.org/content/101/16/5788.long#fn-group-1" title=Footnotes>Previous<br /> Section</a><o:p></o:p></span></p><br /> <p class=MsoNormal style='margin-bottom:0in;margin-bottom:.0001pt;line-height: normal'><span style='font-size:12.0pt;font-family:"Times New Roman","serif"; mso-fareast-font-family:"Times New Roman"'> <o:p></o:p></span></p><br /> <p class=MsoNormal>References</p><br /> <p class=MsoNormal><span style='font-size:12.0pt;line-height:115%'><a href="http://www.pnas.org/content/101/16/5788.long#xref-ref-1-1" title="View reference 1 in text"><span style='font-family:"Cambria Math","serif"; mso-bidi-font-family:"Cambria Math"'>↵</span></a><o:p></o:p></span></p><br /> <p class=MsoNormal><i><span style='font-size:12.0pt;line-height:115%'>Drauz,<br /> K., Waldmann, H. & Roberts, S. 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Biochem. 44 , 1115–1126.</span></i><span style='font-size:12.0pt;line-height:115%'><o:p></o:p></span></p><br /> <p class=MsoNormal><span style='font-size:12.0pt;line-height:115%'><a href="http://www.pnas.org/external-ref?access_num=5968602&link_type=MED">Medline</a><o:p></o:p></span></p><br /> <p class=MsoNormal><o:p> </o:p></p><br /> </div><br /> </body><br /> <br /> </html>http://scholarpharma.blogspot.com/2012/03/development-of-efficient-scalable.html1margipatel02@gmail.com (margipatel02@gmail.com)tag:blogger.com,1999:blog-8563020669307343167.post-4189432943343391147Sun, 29 Jan 2012 14:37:00 +00002012-01-29T06:41:25.648-08:00Cleaning Validation ProtocolCleaning Validation Protocol<b>Cleaning Validation Protocol<br /> </b><br /> <br /> <br /> 1.0 Introduction:<br /> <br /> The Validation of the Cleaning Procedures is establishing documented evidence that the procedure is effective and capable for removing the contaminants associated with previous products, residues of cleaning agents as well as the control of potential microbial contaminants.<br /> <br /> <br /> <br /> The Cleaning Validation is not only ensuring the compliance of the regulatory requirements, but a more important benefit for performing cleaning procedure validation is the identification and the correction of the potential problems which could compromise the safety, efficacy or quality of the subsequent batches of drug product.<br /> <br /> <br /> <br /> 2.0 Objective:<br /> <br /> The objective of the Cleaning Validation is to verify the effectiveness of the cleaning procedure for removal of product residues, degradation products, preservatives, excipients and/or cleaning agents so that the analytical monitoring may be reduced to a minimum in the routine phase, and to ensure that there is no risk associated with cross-contamination of active ingredients.<br /> <br /> <br /> <br /> The objective of Validation of the Cleaning Procedure (SOP No._______________) being used for the cleaning of Machine Name (Machine No. ________________) is to prove that the product contact parts of the Machine Name (Machine No. ________________) have been cleaned and that the contamination level (Chemical and Microbial Contaminants) has been reduced below to an acceptable level.<br /> <br /> <br /> <br /> To achieve these acceptable levels, cleaning procedure (SOP No._______________) need to be established and validated; sampling and analysis will be carried out for this purpose to assure that the cleaning of Machine complies with specified limits.<br /> <br /> Cleaning Validation will verify the effectiveness of cleaning procedure.<br /> <br /> <br /> <br /> 3.0 Scope:<br /> <br /> i. This document on cleaning validation is intended to address special consideration and issues pertaining to validation of cleaning procedure (SOP No._______________) of Machine Name (Machine No. ________________) used for Tablets Compression of Pharmaceutical products.<br /> <br /> <br /> <br /> ii. This document is also intended to establish inspection consistency and uniformity with respect to equipment cleaning procedures.<br /> <br /> <br /> <br /> iii. This document is intended to cover validation of equipment cleaning for the removal of contaminants associated to the previous product, residues of cleaning agents as well as the control of potential microbial contaminants.<br /> <br /> <br /> <br /> 4.0 Responsibility:<br /> <br /> <br /> <br /> i. QA/ QC Manager<br /> <br /> ii. Validation Team Leader<br /> <br /> iii. Validation Officer.<br /> <br /> iv. Representative of Production Department.<br /> <br /> v. Analyst<br /> <br /> vi. Microbiologist<br /> <br /> <br /> <br /> 5.0 Validation Program:<br /> <br /> Equipment cleaning validation may be performed concurrently with actual production steps during process development and bulk manufacturing. Validation programs should be continued through full scale commercial production<br /> <br /> <br /> <br /> The concept “Test-Until-Clean” will be applied. This concept involves cleaning, sampling and testing with repetition of this sequence until an acceptable residue limit is attained.<br /> <br /> <br /> <br /> A validation program generally encompasses at least three consecutive successful replicate to establish that the procedure is reproducibly effective.<br /> <br /> <br /> <br /> If the equipment of the similar size, design and construction is cleaned by the same procedure, studies need not to be conducted on each unit as long as a total of three successful replicates are done on similar piece of equipment; this concept is known as equipment grouping.<br /> <br /> <br /> <br /> 6.0 Change Control:<br /> <br /> Any of the following proposed changes are evaluated fully for their impact on the validated state of the procedure. changes may be,<br /> <br /> <br /> <br /> i. Changing in Machine<br /> <br /> ii. Change in cleaning agents used (if applicable)<br /> <br /> iii. Change in cleaning procedures<br /> <br /> <br /> <br /> If any of the above-cited changes are required it should be performed in accordance with the change control procedure (SOP No. _________________).<br /> <br /> <br /> <br /> After the approval of any change according to procedure, it is required to revalidate the Cleaning Procedure.<br /> <br /> <br /> <br /> 7.0 Acceptance Criteria:<br /> <br /> <br /> <br /> <br /> <br /> S. #<br /> <br /> <br /> Testing Parameter<br /> <br /> <br /> Acceptance Criteria<br /> <br /> 1<br /> <br /> <br /> Physical determination<br /> <br /> <br /> <br /> <br /> The visual examination of the equipment verifying that visible residues or particulate matters.<br /> <br /> 2.<br /> <br /> <br /> Chemical Determination<br /> <br /> <br /> a) NMT 0.1 % of the normal therapeutic dose of any product to appear in the maximum daily dose of the subsequent product.<br /> <br /> b) NMT 10 ppm of any product to appear in the next product.<br /> <br /> c) For certain allergic ingredients, penicillines cephalosporin of steroids and cytotoxic, the limit should be below the limit of detection.<br /> <br /> 3.<br /> <br /> <br /> Microbial Contamination<br /> <br /> <br /> Total aerobic Counts<br /> <br /> a) Bacterial Counts = NMT 20 CFU<br /> <br /> b) Molds = NMT 02 CFU<br /> <br /> <br /> <br /> 8.0 Sampling Procedure:<br /> <br /> <br /> <br /> Direct Surface Sampling (Swab Method):<br /> <br /> <br /> <br /> a) Area difficult to clean and which are reasonably clean can be evaluated by direct surface sampling method (Swab Method), leading to establish a level of contamination or residue per given area i.e. 60 – 100 in2. The residue that are dried out or are insoluble can be sampled by Swab Method.<br /> <br /> <br /> <br /> b) The suitability of the method to be used for sampling and of sampling medium should be determined. The ability to recover the sample accurately may be affected by the choice of sampling method. It is important to assure the sampling medium and solvent (used for extraction from the medium) are satisfactory and can be readily used.<br /> <br /> <br /> <br /> c) For determination of the Microbiological Contamination on surfaces is to use sterile cotton swabs moistened with sterile peptone water, WFI, or Phosphate Buffer. Using sterile forceps and aseptic technique, an area of predetermined size, e.g. 60 - 100 in2, is wiped with a sterile swab. The swab is then aseptically transferred to a sterile tube containing a suitable diluent. The tube is then agitated to suspend any viable microorganisms and aliquots are placed in a semisolid medium to obtain quantitative results.<br /> <br /> 9.0 Cleaning Procedure: SOP No. ________________<br /> <br /> <br /> <br /> i. Switch Off the Machine<br /> <br /> ii. Write down complete cleaning procedure step wise<br /> <br /> iii. After cleaning paste Cleaning Status Label and enter in Logbook<br /> <br /> 10.0 Testing Procedure :<br /> <br /> i. Physical Testing:<br /> <br /> Along with taking samples, it is important to perform visual inspection as well to ensure the process acceptability<br /> <br /> <br /> <br /> ii. Chemical Testing:<br /> <br /> Write down the analytical procedure for determination of traces at least three Active Pharmaceutical Ingredients.<br /> <br /> <br /> <br /> iii. Microbiological Testing:<br /> <br /> <br /> <br /> Swab Test<br /> <br /> · Cotton Swabs prepared on S.S sticks are sterilized.<br /> <br /> · Phosphate buffer pH 7.2 prepared and dispensed 5 ml in each screw capped test<br /> <br /> tubes is sterilized.<br /> <br /> · Material is transferred into sterile area for swab test after disinfection.<br /> <br /> · Remove the sterilized swab, soak in phosphate buffer and touch to the surface to be checked<br /> <br /> · 2 ½ x 2 ½ inch2 area is touched against each soaked swab.<br /> <br /> · Place back the swab into the tube containing phosphate buffer and label the tube with the<br /> <br /> testing part and date.<br /> <br /> · Transfer the tested swab to micro lab. for microbiological test.<br /> <br /> · Pour plate method is used to check the contaminants.<br /> <br /> · Plates are incubated for 48 hours, the results are declared as number of CFU per<br /> <br /> part or surface.<br /> <br /> <br /> <br /> <br /> <br /> 11.0 Overall Validation Procedure:<br /> <br /> <br /> <br /> i. Intimate the Production Department for the Cleaning Validation of Machine Name (Machine No. ________________) before starting the activity through Cleaning Validation Schedule.<br /> <br /> <br /> <br /> ii. After Cleaning of the Machine Name (Machine No. ________________) according to procedure (SOP No. ____________) Production Department inform the Validation Section for conducting the Validation activities.<br /> <br /> <br /> <br /> iii. Validation Officer takes the Swab Sample for Chemical Determination, whereas Microbiologist takes the Swab Sample for Microbiological Determination.<br /> <br /> <br /> <br /> iv. Send the Samples to Quality Control along with Technical Information Sheet for analysis.<br /> <br /> <br /> <br /> v. QCD analyzes the sample according to procedure and provide the results to Validation Section.<br /> <br /> <br /> <br /> vi. Repeat the steps ii, iii and iv after the change of consecutive three different products.<br /> <br /> <br /> <br /> vii. Validation Section analyzes all the results and compiles the report.<br /> <br /> <br /> <br /> viii. If the results comply with the specified limits than the Machine Name (Machine No.<br /> <br /> ________________) is considered as cleaned and the Cleaning Procedure (SOP No. _____________) is considered as Validated.<br /> <br /> <br /> <br /> ix. If the results do not comply with the specified limits, then repeat the overall Validation actives for further two consecutive changes of different products i.e. to provide the validation data of three consecutive API’s<br /> <br /> <br /> <br /> x. If the validation results do not comply with the specification, improve the cleaning procedure and continue it until all the results comply with the specified limits. <br /> <br /> <br /> <br /> 12.0 Inspection Criteria: (For three consecutive products)<br /> <br /> <br /> <br /> <br /> <br /> 12.1 Previous Product<br /> <br /> <br /> <br /> <br /> <br /> Batch No.<br /> <br /> <br /> <br /> <br /> <br /> <br /> While taking samples from Machine Name (Machine No. ________________), note down the following points.<br /> <br /> <br /> <br /> · Description of machine/equipment/area: <br /> <br /> · Major Product contact components: <br /> <br /> · Product Contact Area: <br /> <br /> · Previous Batch completed on: <br /> <br /> · Equipment cleaned on: <br /> <br /> · Detergent / Solvent used: <br /> <br /> · Composition of the detergent used: <br /> <br /> · Cleaning Tools: <br /> <br /> · Ancillary Utilities: <br /> <br /> · Cleaning Cycles: <br /> <br /> · Cleaned by: <br /> <br /> · Supervised by: <br /> <br /> · Sampled by (Chemical) <br /> <br /> · Sampled by (Microbiological) <br /> <br /> · After cleaning the Equipment used on: <br /> <br /> · Subsequent Product: <br /> <br /> · Batch No. <br /> <br /> · Name of API: <br /> <br /> · Batch Size of the subsequent product: <br /> <br /> · Maximum daily dose of the subsequent Product: <br /> <br /> 12.2 Previous Product<br /> <br /> <br /> <br /> <br /> <br /> Batch No.<br /> <br /> <br /> <br /> <br /> <br /> <br /> While taking samples from Machine Name (Machine No. ________________), note down the following points.<br /> <br /> <br /> <br /> · Description of machine/equipment/area: <br /> <br /> · Major Product contact components: <br /> · Product Contact Area: <br /> <br /> · Previous Batch completed on: <br /> · Equipment cleaned on: <br /> <br /> · Detergent / Solvent used: <br /> · Composition of the detergent used: <br /> <br /> · Cleaning Tools: <br /> · Ancillary Utilities: <br /> <br /> · Cleaning Cycles: <br /> <br /> · Cleaned by: <br /> <br /> · Supervised by: <br /> <br /> · Sampled by (Chemical) <br /> <br /> · Sampled by (Microbiological) <br /> <br /> · After cleaning the Equipment used on: <br /> · Subsequent Product: <br /> <br /> · Batch No. <br /> <br /> · Name of API: <br /> <br /> · Batch Size of the subsequent product: <br /> <br /> · Maximum daily dose of the subsequent Product: <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> 12.3 Previous Product<br /> <br /> <br /> <br /> <br /> <br /> Batch No.<br /> <br /> <br /> <br /> <br /> <br /> <br /> While taking samples from Machine Name (Machine No. ________________), note down the following points.<br /> <br /> <br /> <br /> · Description of machine/equipment/area: ____________ <br /> <br /> · Major Product contact components: ______<br /> <br /> · Product Contact Area: ______<br /> <br /> · Previous Batch completed on: ______<br /> <br /> · Equipment cleaned on: ______<br /> <br /> · Detergent / Solvent used: ______<br /> <br /> · Composition of the detergent used: ______<br /> <br /> · Cleaning Tools: ______<br /> <br /> · Ancillary Utilities: <br /> <br /> · Cleaning Cycles: <br /> <br /> · Cleaned by: <br /> <br /> · Supervised by: <br /> <br /> · Sampled by (Chemical) <br /> <br /> · Sampled by (Microbiological) <br /> <br /> · After cleaning the Equipment used on: ______<br /> <br /> · Subsequent Product: ______<br /> <br /> · Batch No. <br /> <br /> · Name of API: ______<br /> <br /> · Batch Size of the subsequent product: ______<br /> <br /> · Maximum daily dose of the subsequent Product: ______<br /> <br /> <br /> <br /> 13.0 Facilities/Responsible Personnel & Documentation:<br /> <br /> <br /> <br /> 13.1 Facilities:<br /> <br /> <br /> <br /> The Validation of Cleaning procedure being used for the cleaning of Machine Name (Machine No. ________________) was performed in ____________ Section of _________ Production at Company Name and Address.<br /> <br /> <br /> <br /> <br /> <br /> 13.2 Identification of Responsible Personnel:<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> Name<br /> <br /> <br /> Job Title<br /> <br /> <br /> Signature<br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> <br /> 13.3 Identification of Documentation:<br /> <br /> <br /> <br /> <br /> <br /> Document Title<br /> <br /> <br /> SOP/QF Number<br /> <br /> Validation Master Plan<br /> <br /> <br /> <br /> <br /> Cleaning Validation (SOP)<br /> <br /> <br /> <br /> <br /> Cleaning Validation Report<br /> <br /> <br /> <br /> <br /> Machine Operating/ Cleaning Procedure (SOP)<br /> <br /> <br /> <br /> <br /> Analytical Result Sheet<br /> <br /> <br /> <br /> <br /> <br /> <br /> 13.4 Other Information: (if any)http://scholarpharma.blogspot.com/2012/01/cleaning-validation-protocol.html7margipatel02@gmail.com (margipatel02@gmail.com)tag:blogger.com,1999:blog-8563020669307343167.post-1253682782138071908Sun, 08 Jan 2012 07:03:00 +00002012-01-07T23:03:45.445-08:00Sampling procedure for purified waterSampling procedure for purified water<b>Sampling procedure for purified water</b><br /> <br /> <b>OBJECTIVE:</b> <br /> <br /> To provide a procedure for sampling of purified water samples for chemical analysis.<br /> <br /> <b>SCOPE:</b><br /> <br /> It applies to purified water from return loop and all points of use.<br /> <br /> <b>RESPONSIBILITY:</b><br /> <br /> Chemist / Officer.<br /> <br /> <b>PROCEDURE:</b> <br /> <br /> Sampling :<br /> <br /> Collect the purified water separately from return loop for complete chemical analysis and<br /> from two points of use in rotation for performing only TOC and conductivity tests. For point<br /> of use and its location refer Annexure – I and for sampling plan refer Annexure – II.<br /> <br /> Initially flush approximate 1 liter of purified water from each point of use and return loop.<br /> <br /> For chemical analysis, collect the purified water in 1000 ml screw cap bottle. Remove the cap of the bottle and rinse with the same purified water prior to sampling. Fill the bottle up to the shoulder so as to collect approximately 900 ml of purified water.<br /> <br /> For TOC analysis, collect the purified water in 100 ml glass stoppered flask dedicated for it.<br /> Remove the stopper of the flask and rinse with the sample to be collected prior to<br /> sampling. Immediately stopper the flask after sampling of the purified water, to avoid<br /> <br /> contamination of atmospheric carbon in sampled purified water. <br /> Bring all collected purified water samples to Q.C. laboratory for testing.http://scholarpharma.blogspot.com/2012/01/sampling-procedure-for-purified-water.html2margipatel02@gmail.com (margipatel02@gmail.com)tag:blogger.com,1999:blog-8563020669307343167.post-3573450978084271388Fri, 06 Jan 2012 04:10:00 +00002012-01-05T20:10:20.676-08:00SOP OF SOPSOP OF SOP<html xmlns:o="urn:schemas-microsoft-com:office:office" xmlns:w="urn:schemas-microsoft-com:office:word" xmlns="http://www.w3.org/TR/REC-html40"> <br /> <br /> <head> <br /> <meta http-equiv=Content-Type content="text/html; charset=windows-1252"> <br /> <meta name=ProgId content=Word.Document> <br /> <meta name=Generator content="Microsoft Word 11"> <br /> <meta name=Originator content="Microsoft Word 11"> <br /> <link rel=File-List href="SOP%20of%20SOP_files/filelist.xml"> <br /> <title>SOP of SOP (SOP on SOP) in Pharmaceuticals</title> <br />  <br /> <style>  </style> <br />  <br /> </head> <br /> <br /> <body lang=EN-US style='tab-interval:.5in'> <br /> <br /> <div class=Section1> <br /> <p class=MsoNormal style='line-height:13.2pt;mso-outline-level:3'><b><span style='font-size:11.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>SOP of SOP (SOP on SOP) in Pharmaceuticals<o:p></o:p></span></b></p> <br /> <p class=MsoNormal style='margin-left:.5in;text-indent:-.5in;line-height:15.6pt'><b><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>1.0</span></b><b><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman";color:#333333'>             </span></b><b><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;mso-bidi-font-family:"Times New Roman"; color:#333333'> </span></b><b><span style='font-size:9.0pt;font-family: Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>OBJECTIVE</span></b><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-size:9.0pt; font-family:Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>To<br /> lay down a procedure for the preparation, approval, authorization, control and<br /> revision of Standard Operating Procedures.<o:p></o:p></span></p> <br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-size:9.0pt; font-family:Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'><o:p> </o:p></span></p> <br /> <p class=MsoNormal style='margin-left:.5in;text-indent:-.5in;line-height:15.6pt'><b><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>2.0</span></b><b><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman";color:#333333'>             </span></b><b><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;mso-bidi-font-family:"Times New Roman"; color:#333333'> </span></b><b><span style='font-size:9.0pt;font-family: Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>SCOPE</span></b><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-size:9.0pt; font-family:Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>This<br /> SOP describes the basic principles, defines the responsibilities and lays down<br /> the procedure for preparing SOPs. This SOP shall be applicable to all the SOPs<br /> at ................<o:p></o:p></span></p> <br /> <p class=MsoNormal style='margin-left:.5in;text-indent:-.5in;line-height:15.6pt'><b><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>3.0</span></b><b><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman";color:#333333'>             </span></b><b><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;mso-bidi-font-family:"Times New Roman"; color:#333333'> </span></b><b><span style='font-size:9.0pt;font-family: Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>RESPONSIBILITY</span></b><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='margin-left:.5in;text-indent:-.5in;line-height:15.6pt'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>3.1       Preparation &<br /> Execution: Executive and above<o:p></o:p></span></p> <br /> <p class=MsoNormal style='margin-left:.5in;text-indent:-.5in;line-height:15.6pt'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>3.2       Approval: Asst. Manager<br /> and above<o:p></o:p></span></p> <br /> <p class=MsoNormal style='margin-left:.5in;text-indent:-.5in;line-height:15.6pt'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>3.3       Authorization: Asst.<br /> General Manager and above<o:p></o:p></span></p> <br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-size:9.0pt; font-family:Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'><o:p> </o:p></span></p> <br /> <p class=MsoNormal style='margin-left:.5in;text-indent:-.5in;line-height:15.6pt'><b><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>4.0</span></b><b><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman";color:#333333'>             </span></b><b><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;mso-bidi-font-family:"Times New Roman"; color:#333333'> </span></b><b><span style='font-size:9.0pt;font-family: Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>ACCOUNTABILITY</span></b><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-size:9.0pt; font-family:Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>Head<br /> of the Concerned Department<o:p></o:p></span></p> <br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-size:9.0pt; font-family:Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'><o:p> </o:p></span></p> <br /> <p class=MsoNormal style='margin-left:.5in;text-indent:-.5in;line-height:15.6pt'><b><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>5.0</span></b><b><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman";color:#333333'>             </span></b><b><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;mso-bidi-font-family:"Times New Roman"; color:#333333'> </span></b><b><span style='font-size:9.0pt;font-family: Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>PROCEDURE</span></b><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='text-align:justify;line-height:15.6pt'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p> </o:p></span></p> <br /> <p class=MsoNormal style='text-align:justify;line-height:15.6pt'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p> </o:p></span></p> <br /> <p class=MsoNormal style='margin-left:.5in;text-align:justify;text-indent:-.5in; line-height:15.6pt'><span style='font-size:9.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>5.1</span><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman";color:#333333'>             </span><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;mso-bidi-font-family:"Times New Roman"; color:#333333'> </span><span style='font-size:9.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>Prepare the SOP on the approved<br /> format on A-4 size paper.<o:p></o:p></span></p> <br /> <p class=MsoNormal style='text-align:justify;line-height:15.6pt'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p> </o:p></span></p> <br /> <p class=MsoNormal style='margin-left:.5in;text-align:justify;text-indent:-.5in; line-height:15.6pt'><span style='font-size:9.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>5.2</span><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman";color:#333333'>             </span><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;mso-bidi-font-family:"Times New Roman"; color:#333333'> </span><span style='font-size:9.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>Prepare the SOPs to<br /> describe the operating procedures and steps.<o:p></o:p></span></p> <br /> <p class=MsoNormal style='text-align:justify;line-height:15.6pt'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p> </o:p></span></p> <br /> <p class=MsoNormal style='margin-left:.5in;text-align:justify;text-indent:-.5in; line-height:15.6pt'><span style='font-size:9.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>5.3</span><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman";color:#333333'>             </span><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;mso-bidi-font-family:"Times New Roman"; color:#333333'> </span><span style='font-size:9.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>Write all the SOPs in<br /> clear, unambiguous language, easy to understand and easy to follow.<o:p></o:p></span></p> <br /> <p class=MsoNormal style='text-align:justify;line-height:15.6pt'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p> </o:p></span></p> <br /> <p class=MsoNormal style='margin-left:.5in;text-align:justify;text-indent:-.5in; line-height:15.6pt'><span style='font-size:9.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>5.4</span><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman";color:#333333'>             </span><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;mso-bidi-font-family:"Times New Roman"; color:#333333'> </span><span style='font-size:9.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>Write the SOPs under the<br /> following sub-headings:<o:p></o:p></span></p> <br /> <p class=MsoNormal style='text-align:justify;line-height:15.6pt'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p> </o:p></span></p> <br /> <p class=MsoNormal style='text-align:justify;line-height:15.6pt'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p> </o:p></span></p> <br /> <p class=MsoNormal style='margin-left:30.15pt;text-align:justify;text-indent: -30.15pt;line-height:15.6pt'><b><span style='font-size:9.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>1.0</span></b><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman";color:#333333'>         </span></b><b><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;mso-bidi-font-family:"Times New Roman"; color:#333333'> </span></b><b><span style='font-size:9.0pt;font-family: Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>OBJECTIVE</span></b><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='margin-left:30.15pt;text-align:justify;text-indent: -30.15pt;line-height:15.6pt'><b><span style='font-size:9.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>2.0</span></b><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman";color:#333333'>         </span></b><b><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;mso-bidi-font-family:"Times New Roman"; color:#333333'> </span></b><b><span style='font-size:9.0pt;font-family: Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>SCOPE</span></b><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='margin-left:30.15pt;text-align:justify;text-indent: -30.15pt;line-height:15.6pt'><b><span style='font-size:9.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>3.0</span></b><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman";color:#333333'>         </span></b><b><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;mso-bidi-font-family:"Times New Roman"; color:#333333'> </span></b><b><span style='font-size:9.0pt;font-family: Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>RESPONSIBILITY</span></b><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='margin-left:30.15pt;text-align:justify;text-indent: -30.15pt;line-height:15.6pt'><b><span style='font-size:9.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>4.0</span></b><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman";color:#333333'>         </span></b><b><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;mso-bidi-font-family:"Times New Roman"; color:#333333'> </span></b><b><span style='font-size:9.0pt;font-family: Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>ACCOUNTABILITY</span></b><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='margin-left:30.15pt;text-align:justify;text-indent: -30.15pt;line-height:15.6pt'><b><span style='font-size:9.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>5.0</span></b><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman";color:#333333'>         </span></b><b><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;mso-bidi-font-family:"Times New Roman"; color:#333333'> </span></b><b><span style='font-size:9.0pt;font-family: Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>PROCEDURE</span></b><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='margin-left:30.15pt;text-align:justify;text-indent: -30.15pt;line-height:15.6pt'><b><span style='font-size:9.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>6.0</span></b><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman";color:#333333'>         </span></b><b><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;mso-bidi-font-family:"Times New Roman"; color:#333333'> </span></b><b><span style='font-size:9.0pt;font-family: Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>REFERENCES</span></b><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='margin-left:30.15pt;text-align:justify;text-indent: -30.15pt;line-height:15.6pt'><b><span style='font-size:9.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>7.0</span></b><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman";color:#333333'>         </span></b><b><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;mso-bidi-font-family:"Times New Roman"; color:#333333'> </span></b><b><span style='font-size:9.0pt;font-family: Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>ANNEXURES</span></b><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='margin-left:30.15pt;text-align:justify;text-indent: -30.15pt;line-height:15.6pt'><b><span style='font-size:9.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>8.0</span></b><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman";color:#333333'>         </span></b><b><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;mso-bidi-font-family:"Times New Roman"; color:#333333'> </span></b><b><span style='font-size:9.0pt;font-family: Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>ABBREVIATIONS</span></b><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p></o:p></span></p> <br /> <span style='font-size:12.0pt;font-family:"Times New Roman";mso-fareast-font-family: "Times New Roman";mso-bidi-font-family:"Times New Roman";color:#333333; mso-ansi-language:EN-US;mso-fareast-language:EN-US;mso-bidi-language:HI'><br clear=all style='mso-special-character:line-break;page-break-before:always'> <br /> </span> <br /> <br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-size:9.0pt; font-family:Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'><o:p> </o:p></span></p> <br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-size:9.0pt; font-family:Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'><o:p> </o:p></span></p> <br /> <p class=MsoNormal style='margin-left:.75in;text-indent:-.75in;line-height: 15.6pt'><b><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family: "Times New Roman";color:#333333'>5.4.1</span></b><b><span style='font-size: 9.0pt;mso-bidi-font-family:"Times New Roman";color:#333333'>                   </span></b><b><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;mso-bidi-font-family:"Times New Roman"; color:#333333'> </span></b><b><span style='font-size:9.0pt;font-family: Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>OBJECTIVE</span></b><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='text-align:justify;line-height:15.6pt'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>Write here the reason for preparing the SOP in one sentence or<br /> maximum two sentences starting with a letter</span><span style='font-size:9.0pt; mso-bidi-font-size:12.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'> </span><b><span style='font-size:9.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>‘To’</span></b><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>.<o:p></o:p></span></p> <br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-size:9.0pt; font-family:Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'><o:p> </o:p></span></p> <br /> <p class=MsoNormal style='margin-left:.75in;text-indent:-.75in;line-height: 15.6pt'><b><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family: "Times New Roman";color:#333333'>5.4.2</span></b><b><span style='font-size: 9.0pt;mso-bidi-font-family:"Times New Roman";color:#333333'>                   </span></b><b><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;mso-bidi-font-family:"Times New Roman"; color:#333333'> </span></b><b><span style='font-size:9.0pt;font-family: Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>SCOPE</span></b><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='text-align:justify;line-height:15.6pt'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>This Section defines the applicability of the SOP and also<br /> specifies departments, areas or sections to which this SOP shall be applicable.<o:p></o:p></span></p> <br /> <p class=MsoNormal style='text-indent:.75in;line-height:15.6pt'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p> </o:p></span></p> <br /> <p class=MsoNormal style='margin-left:.75in;text-indent:-.75in;line-height: 15.6pt'><b><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family: "Times New Roman";color:#333333'>5.4.3</span></b><b><span style='font-size: 9.0pt;mso-bidi-font-family:"Times New Roman";color:#333333'>                   </span></b><b><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;mso-bidi-font-family:"Times New Roman"; color:#333333'> </span></b><b><span style='font-size:9.0pt;font-family: Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>RESPONSIBILITY</span></b><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='text-align:justify;line-height:15.6pt'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>Write here the designation of the person / persons who are<br /> directly responsible for the operations mentioned in the</span><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'> </span><b><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>‘Objective’</span></b><span style='font-size:9.0pt;mso-bidi-font-size: 12.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'> </span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>of the SOP.<o:p></o:p></span></p> <br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-size:9.0pt; font-family:Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'><o:p> </o:p></span></p> <br /> <p class=MsoNormal style='margin-left:.75in;text-indent:-.75in;line-height: 15.6pt'><b><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family: "Times New Roman";color:#333333'>5.4.4</span></b><b><span style='font-size: 9.0pt;mso-bidi-font-family:"Times New Roman";color:#333333'>                   </span></b><b><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;mso-bidi-font-family:"Times New Roman"; color:#333333'> </span></b><b><span style='font-size:9.0pt;font-family: Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>ACCOUNTABILITY</span></b><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='text-align:justify;line-height:15.6pt'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>Write here the Head of the Department who is accountable for<br /> compliance of the SOP.<o:p></o:p></span></p> <br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-size:9.0pt; font-family:Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'><o:p> </o:p></span></p> <br /> <p class=MsoNormal style='margin-left:.75in;text-indent:-.75in;line-height: 15.6pt'><b><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family: "Times New Roman";color:#333333'>5.4.5</span></b><b><span style='font-size: 9.0pt;mso-bidi-font-family:"Times New Roman";color:#333333'>                   </span></b><b><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;mso-bidi-font-family:"Times New Roman"; color:#333333'> </span></b><b><span style='font-size:9.0pt;font-family: Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>PROCEDURE</span></b><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='margin-left:71.1pt;text-align:justify;text-indent: -71.1pt;line-height:15.6pt'><span style='font-size:9.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>     <br /> 5.4.5.1   Write the procedure/method in short sentences. Do not write<br /> the instructions in long paragraphs.<o:p></o:p></span></p> <br /> <p class=MsoNormal style='text-align:justify;line-height:15.6pt'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p> </o:p></span></p> <br /> <p class=MsoNormal style='margin-left:54.9pt;text-align:justify;text-indent: -54.9pt;line-height:15.6pt'><span style='font-size:9.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>5.4.5.2   <br />  Mention all the checks to be carried out, records to be maintained,<br /> frequency of various operations, checks and special precautions, if any.<o:p></o:p></span></p> <br /> <p class=MsoNormal style='text-align:justify;line-height:15.6pt'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>5.4.5.4       Enclose all the<br /> Annexures with SOP if applicable.<o:p></o:p></span></p> <br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-size:9.0pt; font-family:Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'><o:p> </o:p></span></p> <br /> <p class=MsoNormal style='margin-left:.75in;text-indent:-.75in;line-height: 15.6pt'><b><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family: "Times New Roman";color:#333333'>5.4.6</span></b><b><span style='font-size: 9.0pt;mso-bidi-font-family:"Times New Roman";color:#333333'>                   </span></b><b><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;mso-bidi-font-family:"Times New Roman"; color:#333333'> </span></b><b><span style='font-size:9.0pt;font-family: Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>REFERENCES</span></b><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-size:9.0pt; font-family:Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>Mention<br /> a list of references or any other guidance documents based on which the SOP has<br /> been prepared. If there is no reference for the SOP, mention ‘Not Applicable’<br /> under this subheading.<o:p></o:p></span></p> <br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-size:9.0pt; font-family:Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'><o:p> </o:p></span></p> <br /> <p class=MsoNormal style='margin-left:.75in;text-indent:-.75in;line-height: 15.6pt'><b><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family: "Times New Roman";color:#333333'>5.4.7</span></b><b><span style='font-size: 9.0pt;mso-bidi-font-family:"Times New Roman";color:#333333'>                   </span></b><b><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;mso-bidi-font-family:"Times New Roman"; color:#333333'> </span></b><b><span style='font-size:9.0pt;font-family: Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>ANNEXURES</span></b><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='margin-left:.75in;text-indent:-.75in;line-height: 15.6pt'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family: "Times New Roman";color:#333333'>                 <br /> Mention a list of all Annexures enclosed in the SOP. If there is no Annexure in<br /> the SOP, mention ‘Not Applicable’ under this subheading.<o:p></o:p></span></p> <br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-size:9.0pt; font-family:Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'><o:p> </o:p></span></p> <br /> <p class=MsoNormal style='margin-left:63.0pt;text-indent:-63.0pt;line-height: 15.6pt'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family: "Times New Roman";color:#333333'><o:p> </o:p></span></p> <br /> <p class=MsoNormal style='margin-left:63.0pt;text-indent:-63.0pt;line-height: 15.6pt'><b><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family: "Times New Roman";color:#333333'>5.4.8</span></b><b><span style='font-size: 9.0pt;mso-bidi-font-family:"Times New Roman";color:#333333'>       </span></b><b><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;mso-bidi-font-family:"Times New Roman"; color:#333333'> </span></b><b><span style='font-size:9.0pt;font-family: Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>ABBREVIATIONS :</span></b><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-size:9.0pt; font-family:Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>Mention<br /> a list of all abbreviations & their full forms/descriptions used in the<br /> SOP. If there is no Abbreviation in the SOP, mention ‘Not Applicable’ under<br /> this subheading.<o:p></o:p></span></p> <br /> <p class=MsoNormal style='text-align:justify;line-height:15.6pt'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p> </o:p></span></p> <br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-size:9.0pt; font-family:Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'><o:p> </o:p></span></p> <br /> <p class=MsoNormal style='margin-left:.95in;text-indent:-.95in;line-height: 15.6pt'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family: "Times New Roman";color:#333333'>5.5</span><span style='font-size:9.0pt; mso-bidi-font-family:"Times New Roman";color:#333333'>                </span><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;mso-bidi-font-family:"Times New Roman"; color:#333333'> </span><span style='font-size:9.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>Write the SOP in English<br /> (If required, some of the SOPs shall be written in local language i.e Hindi).<o:p></o:p></span></p> <br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-size:9.0pt; font-family:Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'><o:p> </o:p></span></p> <br /> <p class=MsoNormal style='margin-left:40.5pt;text-indent:-40.5pt;line-height: 15.6pt'><b><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family: "Times New Roman";color:#333333'>5.6</span></b><b><span style='font-size:9.0pt; mso-bidi-font-family:"Times New Roman";color:#333333'>                </span></b><b><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;mso-bidi-font-family:"Times New Roman"; color:#333333'> </span></b><b><span style='font-size:9.0pt;font-family: Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>FORMAT<br /> REQUIREMENTS :</span></b><span style='font-size:9.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='text-align:justify;line-height:15.6pt'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>Prepare all the SOPs as per specimen format given as Annexure I<br /> to this SOP.<o:p></o:p></span></p> <br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-size:9.0pt; font-family:Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>The<br /> type of font for the contents in SOPs shall be  ‘Times New Roman’</span><b><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'> </span></b><b><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>.</span></b><span style='font-size:9.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>The font size to be used<br /> for contents of SOPs shall be as follows:<o:p></o:p></span></p> <br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-size:9.0pt; font-family:Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'><o:p> </o:p></span></p> <br /> <p class=MsoNormal style='margin-left:40.5pt;text-indent:-40.5pt;line-height: 15.6pt'><b><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family: "Times New Roman";color:#333333'>5.6.1</span></b><b><span style='font-size: 9.0pt;mso-bidi-font-family:"Times New Roman";color:#333333'>          </span></b><b><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;mso-bidi-font-family:"Times New Roman"; color:#333333'> </span></b><b><span style='font-size:9.0pt;font-family: Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>FONTS</span></b><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-size:9.0pt; font-family:Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'><o:p> </o:p></span></p> <br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-size:9.0pt; font-family:Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'><o:p> </o:p></span></p> <br /> <table class=MsoNormalTable border=0 cellspacing=0 cellpadding=0 style='margin-left:.7in;border-collapse:collapse;mso-padding-alt:0in 0in 0in 0in'> <tr style='mso-yfti-irow:0;mso-yfti-firstrow:yes;height:15.35pt'> <td width=432 valign=top style='width:4.5in;border:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:15.35pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;line-height:15.6pt'><b><span style='mso-bidi-font-family: "Times New Roman"'>Content of SOP</span></b><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> </td> <td width=180 valign=top style='width:135.0pt;border:solid windowtext 1.0pt; border-left:none;mso-border-left-alt:inset #EFEFEF .75pt;padding:0in 5.4pt 0in 5.4pt; height:15.35pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;line-height:15.6pt'><b><span style='mso-bidi-font-family: "Times New Roman"'>Size of Font</span></b><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> </td> </tr> <tr style='mso-yfti-irow:1;height:15.35pt'> <td width=612 colspan=2 valign=top style='width:459.0pt;border:solid windowtext 1.0pt; border-top:none;mso-border-top-alt:inset #EFEFEF .75pt;padding:0in 5.4pt 0in 5.4pt; height:15.35pt'> <br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:15.6pt'><b><span style='mso-bidi-font-family:"Times New Roman"'>Header</span></b><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> </td> </tr> <tr style='mso-yfti-irow:2;height:14.25pt'> <td width=432 valign=top style='width:4.5in;border:solid windowtext 1.0pt; border-top:none;mso-border-top-alt:inset #EFEFEF .75pt;padding:0in 5.4pt 0in 5.4pt; height:14.25pt;border-top-width:initial;border-top-style:initial'> <br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:15.6pt'><span style='mso-bidi-font-family:"Times New Roman"'>“STANDARD<br /> OPERATING PROCEDURE” & “TITLE”<o:p></o:p></span></p> </td> <td width=180 valign=top style='width:135.0pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt;height:14.25pt'> <br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:15.6pt'><span style='mso-bidi-font-family:"Times New Roman"'>12<br /> Bold in Upper Case<o:p></o:p></span></p> </td> </tr> <tr style='mso-yfti-irow:3;height:13.15pt'> <td width=432 valign=top style='width:4.5in;border:solid windowtext 1.0pt; border-top:none;mso-border-top-alt:inset #EFEFEF .75pt;padding:0in 5.4pt 0in 5.4pt; height:13.15pt'> <br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:15.6pt'><span style='mso-bidi-font-family:"Times New Roman"'>Torrent<br /> Logo on the right hand corner<o:p></o:p></span></p> </td> <td width=180 valign=top style='width:135.0pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt;height:13.15pt'> <br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:15.6pt'><span style='mso-bidi-font-family:"Times New Roman"'>30<br /> mm (L) x 6 mm(H)<o:p></o:p></span></p> </td> </tr> <tr style='mso-yfti-irow:4;height:14.25pt'> <td width=432 valign=top style='width:4.5in;border:solid windowtext 1.0pt; border-top:none;mso-border-top-alt:inset #EFEFEF .75pt;padding:0in 5.4pt 0in 5.4pt; height:14.25pt'> <br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:15.6pt'><span style='mso-bidi-font-family:"Times New Roman"'>“TORRENT”<br /> ( on top left corner )<o:p></o:p></span></p> </td> <td width=180 valign=top style='width:135.0pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt;height:14.25pt'> <br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:15.6pt'><span style='mso-bidi-font-family:"Times New Roman"'>14<br /> Bold in Upper Case<o:p></o:p></span></p> </td> </tr> <tr style='mso-yfti-irow:5;height:45.6pt'> <td width=432 valign=top style='width:4.5in;border:solid windowtext 1.0pt; border-top:none;mso-border-top-alt:inset #EFEFEF .75pt;padding:0in 5.4pt 0in 5.4pt; height:45.6pt'> <br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:15.6pt'><span style='mso-bidi-font-family:"Times New Roman"'>“Pharmaceutical<br /> Ltd.” “Restricted Circulation” “Location”, “Dept.”, “Area”, “Page”, “SOP<br /> No.”, “Revision No.” “Effective Date”, “Supersedes”, “Review Date”,<br /> “Initiated By”, “Approved By”, “Authorized By”, “Name”, “Signature &<br /> Date”<o:p></o:p></span></p> </td> <td width=180 valign=top style='width:135.0pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt;height:45.6pt'> <br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:15.6pt'><span style='mso-bidi-font-family:"Times New Roman"'>10<br /> Bold in Title Case<o:p></o:p></span></p> </td> </tr> <tr style='mso-yfti-irow:6;height:21.1pt'> <td width=432 valign=top style='width:4.5in;border:solid windowtext 1.0pt; border-top:none;mso-border-top-alt:inset #EFEFEF .75pt;padding:0in 5.4pt 0in 5.4pt; height:21.1pt'> <br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:15.6pt'><span style='mso-bidi-font-family:"Times New Roman"'>Actual<br /> Title ( detailed heading ) of SOP<o:p></o:p></span></p> </td> <td width=180 valign=top style='width:135.0pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt;height:21.1pt'> <br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:15.6pt'><span style='mso-bidi-font-family:"Times New Roman"'>12<br /> Bold in Upper Case<o:p></o:p></span></p> </td> </tr> <tr style='mso-yfti-irow:7;height:14.35pt'> <td width=612 colspan=2 valign=top style='width:459.0pt;border:solid windowtext 1.0pt; border-top:none;mso-border-top-alt:inset #EFEFEF .75pt;padding:0in 5.4pt 0in 5.4pt; height:14.35pt'> <br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; line-height:15.6pt'><b><span style='mso-bidi-font-family:"Times New Roman"'>Body</span></b><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> </td> </tr> <tr style='mso-yfti-irow:8;height:14.25pt'> <td width=432 valign=top style='width:4.5in;border:solid windowtext 1.0pt; border-top:none;mso-border-top-alt:inset #EFEFEF .75pt;padding:0in 5.4pt 0in 5.4pt; height:14.25pt;border-top-width:initial;border-top-style:initial'> <br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; text-align:justify;line-height:15.6pt'><span style='mso-bidi-font-family: "Times New Roman"'>Subheadings<o:p></o:p></span></p> </td> <td width=180 valign=top style='width:135.0pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt;height:14.25pt'> <br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; text-align:justify;line-height:15.6pt'><span style='mso-bidi-font-family: "Times New Roman"'>12 Bold in Upper Case<o:p></o:p></span></p> </td> </tr> <tr style='mso-yfti-irow:9;height:14.25pt'> <td width=432 valign=top style='width:4.5in;border:solid windowtext 1.0pt; border-top:none;mso-border-top-alt:inset #EFEFEF .75pt;padding:0in 5.4pt 0in 5.4pt; height:14.25pt'> <br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; text-align:justify;line-height:15.6pt'><span style='mso-bidi-font-family: "Times New Roman"'>Write up of SOP<o:p></o:p></span></p> </td> <td width=180 valign=top style='width:135.0pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt;height:14.25pt'> <br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; text-align:justify;line-height:15.6pt'><span style='mso-bidi-font-family: "Times New Roman"'>12 in Sentence Case<o:p></o:p></span></p> </td> </tr> <tr style='mso-yfti-irow:10;height:14.25pt'> <td width=612 colspan=2 valign=top style='width:459.0pt;border:solid windowtext 1.0pt; border-top:none;mso-border-top-alt:inset #EFEFEF .75pt;padding:0in 5.4pt 0in 5.4pt; height:14.25pt'> <br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; text-align:justify;line-height:15.6pt'><b><span style='mso-bidi-font-family: "Times New Roman"'>Footer</span></b><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> </td> </tr> <tr style='mso-yfti-irow:11;height:18.15pt'> <td width=432 valign=top style='width:4.5in;border:solid windowtext 1.0pt; border-top:none;mso-border-top-alt:inset #EFEFEF .75pt;padding:0in 5.4pt 0in 5.4pt; height:18.15pt;border-top-width:initial;border-top-style:initial'> <br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; text-align:justify;line-height:15.6pt'><span style='mso-bidi-font-family: "Times New Roman"'>“Format No.”<o:p></o:p></span></p> </td> <td width=180 valign=top style='width:135.0pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt;height:18.15pt'> <br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; text-align:justify;line-height:15.6pt'><span style='mso-bidi-font-family: "Times New Roman"'>10 in Title Case<o:p></o:p></span></p> </td> </tr> <tr style='mso-yfti-irow:12;mso-yfti-lastrow:yes;height:18.15pt'> <td width=432 valign=top style='width:4.5in;border:solid windowtext 1.0pt; border-top:none;mso-border-top-alt:inset #EFEFEF .75pt;padding:0in 5.4pt 0in 5.4pt; height:18.15pt'> <br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; text-align:justify;line-height:15.6pt'><span style='mso-bidi-font-family: "Times New Roman"'>Actual format number<o:p></o:p></span></p> </td> <td width=180 valign=top style='width:135.0pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt;height:18.15pt'> <br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; text-align:justify;line-height:15.6pt'><span style='mso-bidi-font-family: "Times New Roman"'>10 in Upper Case<o:p></o:p></span></p> </td> </tr> </table> <br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-size:9.0pt; font-family:Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'><o:p> </o:p></span></p> <br /> <p class=MsoNormal style='margin-left:80.4pt;text-indent:-80.4pt;line-height: 15.6pt'><b><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family: "Times New Roman";color:#333333'>5.7</span></b><b><span style='font-size:9.0pt; mso-bidi-font-family:"Times New Roman";color:#333333'>          </span></b><b><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;mso-bidi-font-family:"Times New Roman"; color:#333333'> </span></b><b><span style='font-size:9.0pt;font-family: Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>   NUMBERING<br /> SYSTEM OF  SOP</span></b><span style='font-size:9.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-size:9.0pt; font-family:Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'><o:p> </o:p></span></p> <br /> <p class=MsoNormal style='margin-left:40.5pt;text-indent:-40.5pt;line-height: 15.6pt'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family: "Times New Roman";color:#333333'>5.7.1      Each SOP<br /> shall have a unique numbering system. Once number is allocated to any SOP, the<br /> same   number shall not be repeated to other SOP.<o:p></o:p></span></p> <br /> <p class=MsoNormal style='margin-left:40.5pt;text-indent:-40.5pt;line-height: 15.6pt'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family: "Times New Roman";color:#333333'><o:p> </o:p></span></p> <br /> <p class=MsoNormal style='margin-left:40.5pt;text-indent:-40.5pt;line-height: 15.6pt'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family: "Times New Roman";color:#333333'>5.7.2      Each SOP<br /> No. consists of seven alphanumerical characters. For example first SOP prepared<br /> in the QA department shall be numbered as BQA-001.<o:p></o:p></span></p> <br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-size:9.0pt; font-family:Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>5.7.2.1  <br /> 1<sup>st</sup></span><sup><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt; font-family:Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'> </span></sup><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>alpha character indicates the location code where ‘B’ indicates<br /> for Baddi.<o:p></o:p></span></p> <br /> <p class=MsoNormal style='margin-left:42.0pt;text-indent:-42.0pt;line-height: 15.6pt'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family: "Times New Roman";color:#333333'>5.7.2.2</span><span style='font-size:9.0pt; mso-bidi-font-family:"Times New Roman";color:#333333'>     </span><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;mso-bidi-font-family:"Times New Roman"; color:#333333'> </span><span style='font-size:9.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>2<sup>nd</sup></span><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'> </span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>alpha character indicates department code and 3<sup>rd</sup></span><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'> </span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>alpha character indicates subsection/area code  for the<br /> departments mentioned in the point no. 5.7.3.<o:p></o:p></span></p> <br /> <p class=MsoNormal style='margin-left:42.0pt;text-indent:-42.0pt;line-height: 15.6pt'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family: "Times New Roman";color:#333333'>5.7.2.3</span><span style='font-size:9.0pt; mso-bidi-font-family:"Times New Roman";color:#333333'>     </span><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;mso-bidi-font-family:"Times New Roman"; color:#333333'> </span><span style='font-size:9.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>For departments other<br /> than point no. 5.7.3,  2<sup>nd</sup>   & 3<sup>rd</sup></span><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'> </span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>alpha characters indicate department code as mentioned in the<br /> point no. 5.7.4.<o:p></o:p></span></p> <br /> <p class=MsoNormal style='margin-left:42.0pt;text-indent:-42.0pt;line-height: 15.6pt'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family: "Times New Roman";color:#333333'>5.7.2.4</span><span style='font-size:9.0pt; mso-bidi-font-family:"Times New Roman";color:#333333'>     </span><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;mso-bidi-font-family:"Times New Roman"; color:#333333'> </span><span style='font-size:9.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>4<sup>th</sup></span><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'> </span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>character is dash’-‘ for separator.<o:p></o:p></span></p> <br /> <p class=MsoNormal style='margin-left:42.0pt;text-indent:-42.0pt;line-height: 15.6pt'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family: "Times New Roman";color:#333333'>5.7.2.5</span><span style='font-size:9.0pt; mso-bidi-font-family:"Times New Roman";color:#333333'>     </span><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;mso-bidi-font-family:"Times New Roman"; color:#333333'> </span><span style='font-size:9.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>5<sup>th</sup></span><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'> </span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>,6<sup>th</sup></span><span style='font-size:9.0pt;mso-bidi-font-size: 12.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'> </span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>& 7<sup>th</sup></span><span style='font-size:9.0pt; mso-bidi-font-size:12.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'> </span><span style='font-size:9.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>numerical characters<br /> indicate serial number of that particular department code. ‘001’ indicates<br /> first SOP prepared under particular department code.<o:p></o:p></span></p> <br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-size:9.0pt; font-family:Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'><o:p> </o:p></span></p> <br /> <p class=MsoNormal style='margin-left:42.0pt;text-indent:-42.0pt;line-height: 15.6pt'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family: "Times New Roman";color:#333333'>5.7.3</span><span style='font-size:9.0pt; mso-bidi-font-family:"Times New Roman";color:#333333'>           </span><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;mso-bidi-font-family:"Times New Roman"; color:#333333'> </span><span style='font-size:9.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>Department wise Code for<br /> SOP Numbering system for Manufacturing and Quality Control:<o:p></o:p></span></p> <br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-size:9.0pt; font-family:Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'><o:p> </o:p></span></p> <br /> <table class=MsoNormalTable border=0 cellspacing=0 cellpadding=0 style='margin-left:.7in;border-collapse:collapse;mso-padding-alt:0in 0in 0in 0in'> <tr style='mso-yfti-irow:0;mso-yfti-firstrow:yes;page-break-inside:avoid'> <td width=132 valign=top style='width:99.0pt;border:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><b><span style='mso-bidi-font-family: "Times New Roman"'>Department</span></b><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> </td> <td width=96 valign=top style='width:1.0in;border:solid windowtext 1.0pt; border-left:none;mso-border-left-alt:inset #EFEFEF .75pt;padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><b><span style='mso-bidi-font-family: "Times New Roman"'>Department Code</span></b><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> </td> <td width=81 valign=top style='width:60.95pt;border:solid windowtext 1.0pt; border-left:none;mso-border-left-alt:inset #EFEFEF .75pt;padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><b><span style='mso-bidi-font-family: "Times New Roman"'>General</span></b><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> </td> <td width=114 valign=top style='width:85.5pt;border:solid windowtext 1.0pt; border-left:none;mso-border-left-alt:inset #EFEFEF .75pt;padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><b><span style='mso-bidi-font-family: "Times New Roman"'>Operational & Calibration</span></b><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> </td> <td width=93 valign=top style='width:69.55pt;border:solid windowtext 1.0pt; border-left:none;mso-border-left-alt:inset #EFEFEF .75pt;padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><b><span style='mso-bidi-font-family: "Times New Roman"'>Cleaning</span></b><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> </td> <td width=108 valign=top style='width:81.0pt;border:solid windowtext 1.0pt; border-left:none;mso-border-left-alt:inset #EFEFEF .75pt;padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><b><span style='mso-bidi-font-family: "Times New Roman"'>Code for SOP No.</span></b><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> </td> </tr> <tr style='mso-yfti-irow:1;page-break-inside:avoid'> <td width=624 colspan=6 valign=top style='width:6.5in;border:solid windowtext 1.0pt; border-top:none;mso-border-top-alt:inset #EFEFEF .75pt;padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; mso-line-height-alt:8.15pt'><b><span style='mso-bidi-font-family:"Times New Roman"'>Beta<br /> Lactam</span></b><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> </td> </tr> <tr style='mso-yfti-irow:2;page-break-inside:avoid'> <td width=132 valign=top style='width:99.0pt;border:solid windowtext 1.0pt; border-top:none;mso-border-top-alt:inset #EFEFEF .75pt;padding:0in 5.4pt 0in 5.4pt; border-top-width:initial;border-top-style:initial'> <br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; text-align:justify;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>Mfg. & Packing<o:p></o:p></span></p> </td> <td width=96 valign=top style='width:1.0in;border-top:none;border-left:none; border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>B<o:p></o:p></span></p> </td> <td width=81 valign=top style='width:60.95pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>G<o:p></o:p></span></p> </td> <td width=114 valign=top style='width:85.5pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>O<o:p></o:p></span></p> </td> <td width=93 valign=top style='width:69.55pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>C<o:p></o:p></span></p> </td> <td width=108 valign=top style='width:81.0pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>BG/BO/BC<o:p></o:p></span></p> </td> </tr> <tr style='mso-yfti-irow:3;page-break-inside:avoid'> <td width=624 colspan=6 valign=top style='width:6.5in;border:solid windowtext 1.0pt; border-top:none;mso-border-top-alt:inset #EFEFEF .75pt;padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; mso-line-height-alt:8.15pt'><b><span style='mso-bidi-font-family:"Times New Roman"'>Non<br /> Beta Lactam</span></b><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> </td> </tr> <tr style='mso-yfti-irow:4;page-break-inside:avoid'> <td width=132 valign=top style='width:99.0pt;border:solid windowtext 1.0pt; border-top:none;mso-border-top-alt:inset #EFEFEF .75pt;padding:0in 5.4pt 0in 5.4pt; border-top-width:initial;border-top-style:initial'> <br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; text-align:justify;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>Capsules<o:p></o:p></span></p> </td> <td width=96 valign=top style='width:1.0in;border-top:none;border-left:none; border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>C<o:p></o:p></span></p> </td> <td width=81 valign=top style='width:60.95pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>G<o:p></o:p></span></p> </td> <td width=114 valign=top style='width:85.5pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>O<o:p></o:p></span></p> </td> <td width=93 valign=top style='width:69.55pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>C<o:p></o:p></span></p> </td> <td width=108 valign=top style='width:81.0pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>CG/CO/CC<o:p></o:p></span></p> </td> </tr> <tr style='mso-yfti-irow:5;page-break-inside:avoid'> <td width=132 valign=top style='width:99.0pt;border:solid windowtext 1.0pt; border-top:none;mso-border-top-alt:inset #EFEFEF .75pt;padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; text-align:justify;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>Liquid Orals<o:p></o:p></span></p> </td> <td width=96 valign=top style='width:1.0in;border-top:none;border-left:none; border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>L<o:p></o:p></span></p> </td> <td width=81 valign=top style='width:60.95pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>G<o:p></o:p></span></p> </td> <td width=114 valign=top style='width:85.5pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>O<o:p></o:p></span></p> </td> <td width=93 valign=top style='width:69.55pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>C<o:p></o:p></span></p> </td> <td width=108 valign=top style='width:81.0pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>LG/LO/LC<o:p></o:p></span></p> </td> </tr> <tr style='mso-yfti-irow:6;page-break-inside:avoid'> <td width=132 valign=top style='width:99.0pt;border:solid windowtext 1.0pt; border-top:none;mso-border-top-alt:inset #EFEFEF .75pt;padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; text-align:justify;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>Packing<o:p></o:p></span></p> </td> <td width=96 valign=top style='width:1.0in;border-top:none;border-left:none; border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>P<o:p></o:p></span></p> </td> <td width=81 valign=top style='width:60.95pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>G<o:p></o:p></span></p> </td> <td width=114 valign=top style='width:85.5pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>O<o:p></o:p></span></p> </td> <td width=93 valign=top style='width:69.55pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>C<o:p></o:p></span></p> </td> <td width=108 valign=top style='width:81.0pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>PG/PO/PC<o:p></o:p></span></p> </td> </tr> <tr style='mso-yfti-irow:7;page-break-inside:avoid'> <td width=132 valign=top style='width:99.0pt;border:solid windowtext 1.0pt; border-top:none;mso-border-top-alt:inset #EFEFEF .75pt;padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; text-align:justify;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>Quality Control<o:p></o:p></span></p> </td> <td width=96 valign=top style='width:1.0in;border-top:none;border-left:none; border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>Q<o:p></o:p></span></p> </td> <td width=81 valign=top style='width:60.95pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>G<o:p></o:p></span></p> </td> <td width=114 valign=top style='width:85.5pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>O<o:p></o:p></span></p> </td> <td width=93 valign=top style='width:69.55pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>C<o:p></o:p></span></p> </td> <td width=108 valign=top style='width:81.0pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>QG/QO/QC<o:p></o:p></span></p> </td> </tr> <tr style='mso-yfti-irow:8;page-break-inside:avoid'> <td width=132 valign=top style='width:99.0pt;border:solid windowtext 1.0pt; border-top:none;mso-border-top-alt:inset #EFEFEF .75pt;padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; text-align:justify;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>Tablets<o:p></o:p></span></p> </td> <td width=96 valign=top style='width:1.0in;border-top:none;border-left:none; border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>T<o:p></o:p></span></p> </td> <td width=81 valign=top style='width:60.95pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>G<o:p></o:p></span></p> </td> <td width=114 valign=top style='width:85.5pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>O<o:p></o:p></span></p> </td> <td width=93 valign=top style='width:69.55pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>C<o:p></o:p></span></p> </td> <td width=108 valign=top style='width:81.0pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>TG/TO/TC<o:p></o:p></span></p> </td> </tr> <tr style='mso-yfti-irow:9;page-break-inside:avoid'> <td width=624 colspan=6 valign=top style='width:6.5in;border:solid windowtext 1.0pt; border-top:none;mso-border-top-alt:inset #EFEFEF .75pt;padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; mso-line-height-alt:8.15pt'><b><span style='mso-bidi-font-family:"Times New Roman"'>Other<br /> Departments</span></b><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> </td> </tr> <tr style='mso-yfti-irow:10;page-break-inside:avoid'> <td width=132 valign=top style='width:99.0pt;border:solid windowtext 1.0pt; border-top:none;mso-border-top-alt:inset #EFEFEF .75pt;padding:0in 5.4pt 0in 5.4pt; border-top-width:initial;border-top-style:initial'> <br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; text-align:justify;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>Engineering<o:p></o:p></span></p> </td> <td width=96 valign=top style='width:1.0in;border-top:none;border-left:none; border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>E<o:p></o:p></span></p> </td> <td width=81 valign=top style='width:60.95pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>G<o:p></o:p></span></p> </td> <td width=114 valign=top style='width:85.5pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>O<o:p></o:p></span></p> </td> <td width=93 valign=top style='width:69.55pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>C<o:p></o:p></span></p> </td> <td width=108 valign=top style='width:81.0pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>EG/EO/EC<o:p></o:p></span></p> </td> </tr> <tr style='mso-yfti-irow:11;page-break-inside:avoid'> <td width=132 valign=top style='width:99.0pt;border:solid windowtext 1.0pt; border-top:none;mso-border-top-alt:inset #EFEFEF .75pt;padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family:"Times New Roman"'>Safety,<br /> Health & Environment<o:p></o:p></span></p> </td> <td width=96 valign=top style='width:1.0in;border-top:none;border-left:none; border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>S<o:p></o:p></span></p> </td> <td width=81 valign=top style='width:60.95pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>G<o:p></o:p></span></p> </td> <td width=114 valign=top style='width:85.5pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>O<o:p></o:p></span></p> </td> <td width=93 valign=top style='width:69.55pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>C<o:p></o:p></span></p> </td> <td width=108 valign=top style='width:81.0pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>SG/SO/SC<o:p></o:p></span></p> </td> </tr> <tr style='mso-yfti-irow:12;mso-yfti-lastrow:yes;page-break-inside:avoid'> <td width=132 valign=top style='width:99.0pt;border:solid windowtext 1.0pt; border-top:none;mso-border-top-alt:inset #EFEFEF .75pt;padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family:"Times New Roman"'>Ware<br /> House<o:p></o:p></span></p> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family:"Times New Roman"'>(<br /> RM, PM, FG Quarantine )<o:p></o:p></span></p> </td> <td width=96 valign=top style='width:1.0in;border-top:none;border-left:none; border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>W<o:p></o:p></span></p> </td> <td width=81 valign=top style='width:60.95pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>G<o:p></o:p></span></p> </td> <td width=114 valign=top style='width:85.5pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>O<o:p></o:p></span></p> </td> <td width=93 valign=top style='width:69.55pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>C<o:p></o:p></span></p> </td> <td width=108 valign=top style='width:81.0pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>WG/WO/WC<o:p></o:p></span></p> </td> </tr> </table> <br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-size:9.0pt; font-family:Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'><o:p> </o:p></span></p> <br /> <p class=MsoNormal style='margin-left:38.4pt;text-indent:-38.4pt;line-height: 15.6pt'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family: "Times New Roman";color:#333333'>5.7.4</span><span style='font-size:9.0pt; mso-bidi-font-family:"Times New Roman";color:#333333'>             </span><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;mso-bidi-font-family:"Times New Roman"; color:#333333'> </span><span style='font-size:9.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>Department wise Code for<br /> SOP Numbering system for other departments:<o:p></o:p></span></p> <br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-size:9.0pt; font-family:Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'><o:p> </o:p></span></p> <br /> <table class=MsoNormalTable border=0 cellspacing=0 cellpadding=0 style='margin-left:59.4pt;border-collapse:collapse;mso-padding-alt:0in 0in 0in 0in'> <tr style='mso-yfti-irow:0;mso-yfti-firstrow:yes'> <td width=492 valign=top style='width:369.0pt;border:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><b><span style='mso-bidi-font-family: "Times New Roman"'>Department</span></b><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> </td> <td width=108 valign=top style='width:81.0pt;border:solid windowtext 1.0pt; border-left:none;mso-border-left-alt:inset #EFEFEF .75pt;padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><b><span style='mso-bidi-font-family: "Times New Roman"'>Code for SOP No.</span></b><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> </td> </tr> <tr style='mso-yfti-irow:1'> <td width=492 valign=top style='width:369.0pt;border:solid windowtext 1.0pt; border-top:none;mso-border-top-alt:inset #EFEFEF .75pt;padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family:"Times New Roman"'>Accounts<o:p></o:p></span></p> </td> <td width=108 valign=top style='width:81.0pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>AC<o:p></o:p></span></p> </td> </tr> <tr style='mso-yfti-irow:2'> <td width=492 valign=top style='width:369.0pt;border:solid windowtext 1.0pt; border-top:none;mso-border-top-alt:inset #EFEFEF .75pt;padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family:"Times New Roman"'>Administration<o:p></o:p></span></p> </td> <td width=108 valign=top style='width:81.0pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>AD<o:p></o:p></span></p> </td> </tr> <tr style='mso-yfti-irow:3'> <td width=492 valign=top style='width:369.0pt;border:solid windowtext 1.0pt; border-top:none;mso-border-top-alt:inset #EFEFEF .75pt;padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family:"Times New Roman"'>Human<br /> Resources & Development<o:p></o:p></span></p> </td> <td width=108 valign=top style='width:81.0pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>HR<o:p></o:p></span></p> </td> </tr> <tr style='mso-yfti-irow:4'> <td width=492 valign=top style='width:369.0pt;border:solid windowtext 1.0pt; border-top:none;mso-border-top-alt:inset #EFEFEF .75pt;padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family:"Times New Roman"'>Information<br /> Technology<o:p></o:p></span></p> </td> <td width=108 valign=top style='width:81.0pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>IT<o:p></o:p></span></p> </td> </tr> <tr style='mso-yfti-irow:5'> <td width=492 valign=top style='width:369.0pt;border:solid windowtext 1.0pt; border-top:none;mso-border-top-alt:inset #EFEFEF .75pt;padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family:"Times New Roman"'>Production<br /> Planning & Supply Chain<o:p></o:p></span></p> </td> <td width=108 valign=top style='width:81.0pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>PP<o:p></o:p></span></p> </td> </tr> <tr style='mso-yfti-irow:6'> <td width=492 valign=top style='width:369.0pt;border:solid windowtext 1.0pt; border-top:none;mso-border-top-alt:inset #EFEFEF .75pt;padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family:"Times New Roman"'>Purchase<o:p></o:p></span></p> </td> <td width=108 valign=top style='width:81.0pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>PU<o:p></o:p></span></p> </td> </tr> <tr style='mso-yfti-irow:7;mso-yfti-lastrow:yes'> <td width=492 valign=top style='width:369.0pt;border:solid windowtext 1.0pt; border-top:none;mso-border-top-alt:inset #EFEFEF .75pt;padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family:"Times New Roman"'>Quality<br /> Assurance<o:p></o:p></span></p> </td> <td width=108 valign=top style='width:81.0pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; mso-border-top-alt:inset #EFEFEF .75pt;mso-border-left-alt:inset #EFEFEF .75pt; padding:0in 5.4pt 0in 5.4pt'> <br /> <p class=MsoNormal align=center style='mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;text-align:center;mso-line-height-alt:8.15pt'><span style='mso-bidi-font-family: "Times New Roman"'>QA<o:p></o:p></span></p> </td> </tr> </table> <br /> <p class=MsoNormal style='text-indent:16.5pt;line-height:15.6pt'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p> </o:p></span></p> <br /> <p class=MsoNormal style='margin-left:38.4pt;text-indent:-38.4pt;line-height: 15.6pt'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family: "Times New Roman";color:#333333'>5.7.5</span><span style='font-size:9.0pt; mso-bidi-font-family:"Times New Roman";color:#333333'>             </span><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;mso-bidi-font-family:"Times New Roman"; color:#333333'> </span><span style='font-size:9.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>For example, the first<br /> General SOP of Tablet department shall be numbered as BTG-001.<o:p></o:p></span></p> <br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-size:9.0pt; font-family:Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'><o:p> </o:p></span></p> <br /> <p class=MsoNormal style='line-height:15.6pt'><b><span style='font-size:9.0pt; font-family:Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>  <br /> 5.8        CONTENTS OF HEADER</span></b><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='line-height:15.6pt'><b><span style='font-size:9.0pt; font-family:Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>  </span></b><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='margin-left:45.0pt;text-indent:-45.0pt;line-height: 15.6pt'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family: "Times New Roman";color:#333333'>5.8.1</span><span style='font-size:9.0pt; mso-bidi-font-family:"Times New Roman";color:#333333'>             </span><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;mso-bidi-font-family:"Times New Roman"; color:#333333'> </span><b><span style='font-size:9.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>Location :</span></b><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'> </span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>The name of location of the plant  for which SOP is<br /> applicable.<o:p></o:p></span></p> <br /> <p class=MsoNormal style='margin-left:45.0pt;text-indent:-45.0pt;line-height: 15.6pt'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family: "Times New Roman";color:#333333'>5.8.2</span><span style='font-size:9.0pt; mso-bidi-font-family:"Times New Roman";color:#333333'>             </span><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;mso-bidi-font-family:"Times New Roman"; color:#333333'> </span><b><span style='font-size:9.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>Department :</span></b><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'> </span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>The name of the Department for which SOP is applicable.<o:p></o:p></span></p> <br /> <p class=MsoNormal style='margin-left:45.0pt;text-indent:-45.0pt;line-height: 15.6pt'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family: "Times New Roman";color:#333333'>5.8.3</span><span style='font-size:9.0pt; mso-bidi-font-family:"Times New Roman";color:#333333'>             </span><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;mso-bidi-font-family:"Times New Roman"; color:#333333'> </span><b><span style='font-size:9.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>Area:</span></b><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'> </span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>The area / sub-section of the Department shall be mentioned<br /> wherever applicable.<o:p></o:p></span></p> <br /> <p class=MsoNormal style='margin-left:45.0pt;text-indent:-45.0pt;line-height: 15.6pt'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family: "Times New Roman";color:#333333'>5.8.4</span><span style='font-size:9.0pt; mso-bidi-font-family:"Times New Roman";color:#333333'>             </span><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;mso-bidi-font-family:"Times New Roman"; color:#333333'> </span><b><span style='font-size:9.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>Title:</span></b><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'> </span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>Detailed heading of the SOP.<o:p></o:p></span></p> <br /> <p class=MsoNormal style='margin-left:45.0pt;text-indent:-45.0pt;line-height: 15.6pt'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family: "Times New Roman";color:#333333'>5.8.5</span><span style='font-size:9.0pt; mso-bidi-font-family:"Times New Roman";color:#333333'>             </span><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;mso-bidi-font-family:"Times New Roman"; color:#333333'> </span><b><span style='font-size:9.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>SOP No.:</span></b><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'> </span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>Unique SOP No. as per procedures described in the point no. 5.7<br /> shall be mentioned here.<o:p></o:p></span></p> <br /> <p class=MsoNormal style='margin-left:45.0pt;text-indent:-45.0pt;line-height: 15.6pt'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family: "Times New Roman";color:#333333'>5.8.6</span><span style='font-size:9.0pt; mso-bidi-font-family:"Times New Roman";color:#333333'>             </span><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;mso-bidi-font-family:"Times New Roman"; color:#333333'> </span><b><span style='font-size:9.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>Revision No. :</span></b><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'> </span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'> Revision No. consists of two numerical characters which<br /> start from ‘00’ with increment in one digit after each revision. ‘00’ indicates<br /> the first issuance of that particular SOP.<o:p></o:p></span></p> <br /> <p class=MsoNormal style='margin-left:45.0pt;text-indent:-45.0pt;line-height: 15.6pt'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family: "Times New Roman";color:#333333'>5.8.7</span><span style='font-size:9.0pt; mso-bidi-font-family:"Times New Roman";color:#333333'>             </span><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;mso-bidi-font-family:"Times New Roman"; color:#333333'> </span><b><span style='font-size:9.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>Effective Date:</span></b><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'> </span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>The effective date shall be stamped by Q.A. after final<br /> authorization before circulating the SOPs.<o:p></o:p></span></p> <br /> <p class=MsoNormal style='margin-left:45.0pt;text-indent:-45.0pt;line-height: 15.6pt'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family: "Times New Roman";color:#333333'>5.8.8</span><span style='font-size:9.0pt; mso-bidi-font-family:"Times New Roman";color:#333333'>             </span><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;mso-bidi-font-family:"Times New Roman"; color:#333333'> </span><b><span style='font-size:9.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>Supersedes:</span></b><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'> </span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>For the first issuance, ‘New introduction’ shall be mentioned in<br /> this column, otherwise  effective date of obsolete ( previous) SOP shall<br /> be mentioned.<o:p></o:p></span></p> <br /> <p class=MsoNormal style='margin-left:45.0pt;text-indent:-45.0pt;line-height: 15.6pt'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family: "Times New Roman";color:#333333'>5.8.9</span><span style='font-size:9.0pt; mso-bidi-font-family:"Times New Roman";color:#333333'>             </span><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;mso-bidi-font-family:"Times New Roman"; color:#333333'> </span><b><span style='font-size:9.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>Review Date:</span></b><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'> </span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>The normal review period will be 2 years from the effective date<br /> of the SOP. For example if any SOP is having effective date “07-10-2004”, its<br /> review date will be “07-10-2006”. Revision of SOPs shall be done as per<br /> procedure mentioned in the point no. 5.13.<o:p></o:p></span></p> <br /> <p class=MsoNormal style='margin-left:45.0pt;text-indent:-45.0pt;line-height: 15.6pt'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family: "Times New Roman";color:#333333'>5.8.10</span><span style='font-size:9.0pt; mso-bidi-font-family:"Times New Roman";color:#333333'>         </span><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;mso-bidi-font-family:"Times New Roman"; color:#333333'> </span><b><span style='font-size:9.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>Page :</span></b><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'> </span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>The  page number shall be mentioned in ‘xx of yy’ format.<o:p></o:p></span></p> <br /> <p class=MsoNormal style='margin-left:45.0pt;text-indent:-45.0pt;line-height: 15.6pt'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family: "Times New Roman";color:#333333'>5.8.11</span><span style='font-size:9.0pt; mso-bidi-font-family:"Times New Roman";color:#333333'>         </span><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;mso-bidi-font-family:"Times New Roman"; color:#333333'> </span><b><span style='font-size:9.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>Signatures :</span></b><b><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'> </span></b><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>The Header</span><b><span style='font-size:9.0pt;mso-bidi-font-size: 12.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'> </span></b><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>comprises of three columns i.e.</span><b><span style='font-size: 9.0pt;mso-bidi-font-size:12.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'> </span></b><b><span style='font-size:9.0pt;font-family: Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>Initiated By,<br /> Approved By & Authorized by.</span></b><span style='font-size:9.0pt; font-family:Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='margin-left:45.0pt;text-align:justify;text-indent: -45.0pt;line-height:15.6pt'><span style='font-size:9.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>              <br /> Each of the three columns consist of 3 rows i.e. Name of the person who signs<br /> the SOP in full signature and the date on which the person signs the SOP.<o:p></o:p></span></p> <br /> <p class=MsoNormal style='margin-left:45.0pt;text-indent:-45.0pt;line-height: 15.6pt'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family: "Times New Roman";color:#333333'>5.8.11.1</span><span style='font-size:9.0pt; mso-bidi-font-family:"Times New Roman";color:#333333'>   </span><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;mso-bidi-font-family:"Times New Roman"; color:#333333'> </span><b><span style='font-size:9.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>Initiated by :</span></b><b><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'> </span></b><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>Designated person, who has initiated  the SOP shall<br /> write  name clearly  with  signature &  date in blue<br /> ink in the column “Initiated By”. <o:p></o:p></span></p> <br /> <p class=MsoNormal style='margin-left:45.0pt;text-indent:-45.0pt;line-height: 15.6pt'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family: "Times New Roman";color:#333333'>5.8.11.2</span><span style='font-size:9.0pt; mso-bidi-font-family:"Times New Roman";color:#333333'>   </span><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;mso-bidi-font-family:"Times New Roman"; color:#333333'> </span><b><span style='font-size:9.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>Approved by:</span></b><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'> </span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>Two persons shall approve the SOP after review. One of them<br /> shall be concerned Department Head and the other shall be Head of Quality<br /> Assurance. They shall write name clearly with signature and date in blue ink.<br /> In case of QA SOPs first approval shall be done by Asst. Manager and above and<br /> second approval shall be done by the Manager and above of the  Quality<br /> Assurance Department.<o:p></o:p></span></p> <br /> <p class=MsoNormal style='margin-left:45.0pt;text-indent:-45.0pt;line-height: 15.6pt'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family: "Times New Roman";color:#333333'>5.8.11.3</span><span style='font-size:9.0pt; mso-bidi-font-family:"Times New Roman";color:#333333'>   </span><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;mso-bidi-font-family:"Times New Roman"; color:#333333'> </span><b><span style='font-size:9.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>Authorized by:</span></b><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'> </span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>The person finally authorizing the SOP, shall sign here.<br /> Authorization shall be done by Location Head, who shall write name clearly with<br /> signature and date in blue ink. In case of QA SOPs, the Location QA Head shall<br /> authorize all the SOPs except the SOP No. BQA-001 (Preparation, Approval,<br /> Authorization, Control and Revision of SOPs). This SOP shall be authorized by<br /> Vice President – Corporate QA.<o:p></o:p></span></p> <br /> <p class=MsoNormal style='margin-left:45.0pt;text-indent:-45.0pt;line-height: 15.6pt'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family: "Times New Roman";color:#333333'><o:p> </o:p></span></p> <br /> <p class=MsoNormal style='margin-left:45.0pt;text-indent:-45.0pt;line-height: 15.6pt'><b><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family: "Times New Roman";color:#333333'>5.9     <br />    CONTENTS OF FOOTER</span></b><span style='font-size:9.0pt; font-family:Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='margin-left:45.0pt;text-align:justify;text-indent: -45.0pt;mso-line-height-alt:7.45pt'><span style='font-size:9.0pt;font-family: Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'><o:p> </o:p></span></p> <br /> <p class=MsoNormal style='margin-left:45.0pt;text-align:justify;text-indent: -45.0pt;mso-line-height-alt:7.45pt'><span style='font-size:9.0pt;font-family: Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>5.9.1      </span><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'> </span><b><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>Format No.:</span></b><span style='font-size:9.0pt;mso-bidi-font-size: 12.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'> </span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>This is a unique number assigned to the format used for<br /> preparation of all SOPs as described in the point no. 5.11.4.<o:p></o:p></span></p> <br /> <p class=MsoNormal style='margin-left:45.0pt;text-align:justify;text-indent: -45.0pt;mso-line-height-alt:7.45pt'><span style='font-size:9.0pt;font-family: Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'><o:p> </o:p></span></p> <br /> <p class=MsoNormal style='margin-left:45.0pt;text-indent:-45.0pt;mso-line-height-alt: 7.45pt'><b><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family: "Times New Roman";color:#333333'>5.10</span></b><b><span style='font-size:9.0pt; mso-bidi-font-family:"Times New Roman";color:#333333'>               </span></b><b><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;mso-bidi-font-family:"Times New Roman"; color:#333333'> </span></b><b><span style='font-size:9.0pt;font-family: Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>GENERATION OF NEW<br /> SOPs</span></b><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family: "Times New Roman";color:#333333'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='margin-left:45.0pt;text-indent:-45.0pt;mso-line-height-alt: 7.45pt'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family: "Times New Roman";color:#333333'><o:p> </o:p></span></p> <br /> <p class=MsoNormal style='margin-left:45.0pt;text-indent:-45.0pt;mso-line-height-alt: 7.45pt'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family: "Times New Roman";color:#333333'>5.10.1</span><span style='font-size:9.0pt; mso-bidi-font-family:"Times New Roman";color:#333333'>         </span><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;mso-bidi-font-family:"Times New Roman"; color:#333333'> </span><span style='font-size:9.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>User dept. shall prepare<br /> the draft SOP as per the procedure described in the point no.5.4 to 5.9. Draft<br /> copy shall be identified by stamping or water mark on each page.<o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-line-height-alt:7.45pt'><span style='font-size: 9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'><o:p> </o:p></span></p> <br /> <p class=MsoNormal style='margin-left:45.0pt;text-indent:-45.0pt;mso-line-height-alt: 7.45pt'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family: "Times New Roman";color:#333333'>5.10.2</span><span style='font-size:9.0pt; mso-bidi-font-family:"Times New Roman";color:#333333'>         </span><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;mso-bidi-font-family:"Times New Roman"; color:#333333'> </span><span style='font-size:9.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>Draft copy shall be<br /> circulated to the responsible persons for its review. The responsible persons<br /> may recommend  for any changes in the text.<o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-line-height-alt:7.45pt'><span style='font-size: 9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'><o:p> </o:p></span></p> <br /> <p class=MsoNormal style='margin-left:45.0pt;text-indent:-45.0pt;line-height: 15.6pt'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family: "Times New Roman";color:#333333'>5.10.3</span><span style='font-size:9.0pt; mso-bidi-font-family:"Times New Roman";color:#333333'>         </span><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;mso-bidi-font-family:"Times New Roman"; color:#333333'> </span><span style='font-size:9.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>Based on the<br /> recommendation, user dept. shall correct the draft SOP and take final print out<br /> for approval and authorization along with Change History Log.<o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-line-height-alt:7.45pt'><span style='font-size: 9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'><o:p> </o:p></span></p> <br /> <p class=MsoNormal style='margin-left:44.1pt;text-indent:-44.1pt;mso-line-height-alt: 7.45pt'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family: "Times New Roman";color:#333333'>5.10.4</span><span style='font-size:9.0pt; mso-bidi-font-family:"Times New Roman";color:#333333'>         </span><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;mso-bidi-font-family:"Times New Roman"; color:#333333'> </span><span style='font-size:9.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>After approval and<br /> authorization, user dept. shall submit the Original Copy ( Master Copy ) of SOP<br /> along with ‘Change History Log’ to QA for control and issuance and shall<br /> destroy the draft SOP.<o:p></o:p></span></p> <br /> <p class=MsoNormal><o:p> </o:p></p> <br /> </div> <br /> </body> <br /> <br /> </html>http://scholarpharma.blogspot.com/2012/01/sop-of-sop.html4margipatel02@gmail.com (margipatel02@gmail.com)tag:blogger.com,1999:blog-8563020669307343167.post-7570339650803055764Fri, 06 Jan 2012 04:01:00 +00002012-01-05T20:01:59.450-08:00Difference among calibrationvalidation and qualificationDifference among calibration, validation & qualification<b>Difference among calibration, validation & qualification</b><br /> <br /> A lot of pharmaceutical professionals are having a big confusion among calibration, validation and qualification, hence I am trying to washout the confusion. I think it will make a clear image about these three concepts.<br /> <br /> <b>Calibration:</b><br /> <br /> The set of operations that establish, under specified conditions, the relationship between values indicated by an instrument or system for measuring (for example, weight, temperature and pH), recording, and controlling, or the values represented by a material measure, and the corresponding known values of a reference standard. Limits for acceptance of the results of measuring should be established. Always remember any reference standard is always used in calibration.<br /> <br /> <b>Validation:</b><br /> <br /> Action of proving and documenting that any process, procedure or method actually and consistently leads to the expected results. It can better understand that the validation is a documented evidence to and done to prove the consistency of the expected results of any process, procedure or method.<br /> <br /> <b>Qualification:</b><br /> <br /> Action of proving and documenting that any premises, systems and equipment are properly installed, and/or work correctly and lead to the expected results. Qualification is often a part (the initial stage) of validation, but the individual qualification steps alone do not constitute process validation. Qualification is a part of validation.http://scholarpharma.blogspot.com/2012/01/difference-among-calibration-validation.html1margipatel02@gmail.com (margipatel02@gmail.com)tag:blogger.com,1999:blog-8563020669307343167.post-3641744191264598540Fri, 06 Jan 2012 03:49:00 +00002012-01-05T19:49:19.627-08:00Preparation of Indicator SolutionsPreparation of Indicator Solutions<html xmlns:v="urn:schemas-microsoft-com:vml" xmlns:o="urn:schemas-microsoft-com:office:office" xmlns:w="urn:schemas-microsoft-com:office:word" xmlns="http://www.w3.org/TR/REC-html40"> <br /> <br /> <head> <br /> <meta http-equiv=Content-Type content="text/html; charset=windows-1252"> <br /> <meta name=ProgId content=Word.Document> <br /> <meta name=Generator content="Microsoft Word 11"> <br /> <meta name=Originator content="Microsoft Word 11"> <br /> <link rel=File-List href="Preparation%20of%20Indicator%20Solutions_files/filelist.xml"> <br /> <link rel=Edit-Time-Data href="Preparation%20of%20Indicator%20Solutions_files/editdata.mso"> <br />  <br /> <title>Preparation of Indicator Solutions </title> <br />  <br /> <style>  </style> <br />  <br /> </head> <br /> <br /> <body lang=EN-US style='tab-interval:.5in'> <br /> <br /> <div class=Section1> <br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; mso-outline-level:3'><b><span style='font-size:13.5pt;mso-bidi-font-family: "Times New Roman"'>Preparation of Indicator Solutions <o:p></o:p></span></b></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family: "Times New Roman"'>Indicators</span></b><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>In the test and<br /> assays of the Pharmacopoeia, indicators are required to indicate the completion<br /> of a <span class=SpellE>chemlcal</span> reaction in volumetric analysis or to<br /> indicate the pH of solutions. Indicators may be substituted for one another<br /> provided the <span class=SpellE>colours</span> change over approximately the<br /> same range of pH but in the event of doubt or dispute as to the equivalence of<br /> indicators for a particular procedure, the indicator specified in the<br /> individual monograph is alone authoritative.</span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Any solvent<br /> required in a <span class=SpellE>determlnation</span> or test in which an<br /> indicator is specified should be previously neutralized to the indicator unless<br /> a blank <span class=SpellE>determlnation</span> is performed or specified.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Given below are<br /> materials which are to be used as indicators and the manner in which solutions<br /> of indicators are to be prepared.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Table 1 lists<br /> the more commonly used pH indicators in ascending order of the lower <span class=SpellE>limlt</span> of their range with the corresponding <span class=SpellE>colour</span> changes.</span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family: "Times New Roman"'>Alizarin Red S; CI 58005; Alizarin S; <span class=SpellE>MordantRedB</span>;<br /> Sodium <span class=SpellE>Alizarine</span> <span class=SpellE>Sulphonate</span>;<br /> 9,l0-dihydro- 3,4-dihydroxy-9, l0-dioxo2- <span class=SpellE>anthrancesulphonic</span> <br /> Acid Monosodium salt:</span></b><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>C<sub>14</sub>H<sub>7</sub>NaO<sub>7</sub>S.H<sub>2</sub>0<br /> = 360.27</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>General<br /> laboratory reagent grade of <span class=GramE>commerce .</span></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Yellowish<br /> brown or orange-yellow powder.</span></span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family: "Times New Roman"'>Alizarin Red S Solution; Alizarin S Solution:</span></b><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'> <br /> A0.1 per cent w/v solution of <i>alizarin red </i>S. Complies with the<br /> following test.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>SENSITIVITY TO<br /> BARIUM - To 5 ml of <i>0.05 M <span class=SpellE>sulphuric</span> acid </i>add<br /> 5 ml of <i>water, </i>50 ml of <i>acetate buffer pH </i>3.7 and 0.5 ml of<i> </i>the<br /> solution under <span class=SpellE>examlnation</span>. Add, <span class=SpellE>dropwise</span>,<br /> <i>0.05 M barium <span class=SpellE>perchlorate</span>; </i>the <span class=SpellE>colour</span> changes from yellow to orange-red.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=SpellE><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'>Azo</span></b></span><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'> Violet; <span class=SpellE>Magneson</span>;<br /> 4-(p-<span class=SpellE>Nitrophenylazo</span><span class=GramE>)resorcinol</span>:</span></b><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>C12H9N304=259.22</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Red<br /> powder; mp, about 1930, with decomposition.</span></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family: "Times New Roman"'>Brilliant Green; CI 42040; Malachite Green G; Basic Green 1:</span></b><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>C<sub>27</sub>H<sub>34</sub>N<sub>2</sub>O<sub>4</sub>S=482.64</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Technical<br /> Grade of commerce.</span></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Small,<br /> glistening golden crystals.</span></span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family: "Times New Roman"'>Brilliant Green Solution:</span></b><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'> A 0.5 per cent<br /> w/v solution of <i>brilliant green </i>in <i>glacial acetic acid.</i></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=SpellE><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'>Bromocresol</span></b></span><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'> Green; <span class=SpellE>Bromocresol</span> <br /> Blue; <i>4<span class=GramE>,4</span>-(3H-2,1</i>Benzoxathiol-3-ylidene)<span class=SpellE>bis</span>(2,6-dibromo-m-cresol) S,S-dioxide:</span></b><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>C<sub>21</sub>H<sub>I4</sub>Br<sub>4</sub>O<sub>5</sub>S=<br /> 698.01</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>White<br /> or pale buff-<span class=SpellE>coloured</span> powder.</span></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal align=center style='text-align:center'><span style='mso-bidi-font-family:"Times New Roman"'><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj5hs5jTTJc_-a0nQzv9Y2cb_kI3p7Npfzo0VdhoZaRkHDD6NEZs67lvlLGGhgLZt9JczCb4E2hq94jUV04xQbT64Ddn7EQObajIhXmkvdfWK1uezauxEEM3MetjACuHyTzNW_4oGX6zc4/s1600/indicator.bmp"><span style='font-family:Arial;text-decoration:none;text-underline:none'><![if !vml]><img border=0 width=288 height=517 src="Preparation%20of%20Indicator%20Solutions_files/image001.jpg" kca=true v:shapes="_x0000_i1025"><![endif]></span></a><o:p></o:p></span></p> <br /> <p class=MsoNormal style='margin-bottom:12.0pt'><span style='mso-bidi-font-family: "Times New Roman"'><o:p> </o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=SpellE><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'>Bromocresol</span></b></span><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'> Green Reagent:</span></b><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'> <br /> Prepare a phosphate buffer solution by dissolving 43.0 g of <i>sodium <span class=SpellE>dihydrogen</span> phosphate</i> and 2.0 g of <i>anhydrous sodium<br /> phosphate </i>in sufficient <i>water</i> to make 1000 ml. Dissolve 0.2 g of <span class=SpellE><i>bromocresol</i></span><i> green </i>in 30 ml of <i>water </i>and<br /> 6.5 ml of <i>0.1 M sodium hydroxide. </i>Dilute to 500 ml with the phosphate<br /> buffer solution, <span class=SpellE>mlx</span> and adjust the pH to 4.6 with <i>0.1<br /> M hydrochloric acid.</i></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=SpellE><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'>Bromocresol</span></b></span><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'> Green Solution:</span></b><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'> <br /> Dissolve 50 mg of <span class=SpellE><i>bromocresol</i></span><i> green </i>in<br /> 0.72 ml of <i>0.1 M sodium hydroxide </i>and 20 ml of<i> ethanol </i>(95 <i>per<br /> cent). </i>After solution is <span class=GramE>effected</span>, add sufficient<i> <br /> water </i>to produce 100 ml.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Complies<br /> with the following test.</span></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>SENSITIVITY - <span class=GramE>A</span> <span class=SpellE>mlxture</span> of 0.2 ml of the sol <span class=SpellE>ution</span> and 100 ml of <i>carbon dioxide-free water </i>is<br /> blue. Not more than 0.2 ml of <i>0.02 M hydrochloric acid </i>is required to<br /> change the <span class=SpellE>colour</span> of the solution to yellow.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=SpellE><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'>Bromocresol</span></b></span><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'> Purple; 4<span class=GramE>,4'</span> <br /> <i>-(3H-2, </i>1-Benzoxathiol-3-ylidene)<span class=SpellE>bis</span>(6-bromo-o-cresol)<br /> S,S-dioxide: </span></b><span style='font-size:9.0pt;font-family:Arial; mso-bidi-font-family:"Times New Roman"'>C<sub>2I</sub>H<sub>16</sub>Br<sub>2</sub>O<sub>5</sub>S=<br /> 540.23</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>White<br /> to pink, crystalline powder.</span></span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=SpellE><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'>Bromocresol</span></b></span><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'> Purple Solution:</span></b><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'> <br /> Dissolve 50 mg of <span class=SpellE><i>bromocresol</i></span><i> purple </i>in<br /> 0.92 ml of <i>0.1 M sodium hydroxide </i>and 20 ml of<i> ethanol </i>(95 <i>per<br /> cent). </i>After solution is <span class=GramE>effected</span>, add sufficient<i> <br /> water </i>to produce 100 ml.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Complies<br /> with the following test.</span></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>SENSITIVITY - <span class=GramE>A</span> <span class=SpellE>mlxture</span> of 0.2 ml of the<br /> solution and 100 ml of <i>carbon dioxide-free water </i>to which 0.05 ml of <i>0.02<br /> M sodium</i> <i>hydroxide </i>has been added is bluish violet. Not more than<br /> 0.2 ml of <i>0.02 M hydrochloric acid </i>is required to change the <span class=SpellE>colour</span> to yellow.</span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=SpellE><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'>Bromocresol</span></b></span><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'> Purple Solution,<br /> Phosphate-buffered:</span></b><span style='font-size:9.0pt;font-family:Arial; mso-bidi-font-family:"Times New Roman"'> Dissolve 43 g of <i>potassium <span class=SpellE>dihydrogen</span> phosphate </i>and 5 g of <i>sodium</i> <i>phosphate<br /> </i>in <i>water </i>to make 1000 ml. Adjust the pH of the solution to 5.3 ±<br /> 0.1, if necessary (Solution A). Dissolve 0.4 g of <span class=SpellE><i>bromocresol</i></span><i> <br /> purple </i>in 30 ml of <i>water, </i>add 6.3 ml of <i>0.1 M sodium hydroxide </i>and<br /> dilute with <i>water </i>to make 500 ml (Solution B). Shake equal volumes of<br /> solution <span class=GramE>A</span>, solution B and <i>chloroform </i>in a<br /> separator, allow the layers to separate and discard the chloroform. If<br /> appreciable <span class=SpellE>colour</span> is extracted by the chloroform,<br /> repeat with additional quantities of <i>chloroform </i>until no further <span class=SpellE>colour</span> is extracted.</span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=SpellE><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'>Bromophenol</span></b></span><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'> Blue; 4<span class=GramE>,4'</span> <br /> <i>-(3H- </i>2,1- <span class=SpellE>Benzoxathiol</span>- 3-ylidene)<span class=SpellE>bis</span>(2,6-dibromophenol) S,S-dioxide:</span></b><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'> <br /> C<sub>19</sub>H<sub>10</sub>Br<sub>4</sub>O<sub>5</sub>S= 669.96</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Pinkish<br /> crystals.</span></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=SpellE><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'>Bromophenol</span></b></span><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'> Blue Solution; Strong <span class=SpellE>Bromophenol</span> Blue Solution; <span class=SpellE>Ethanolic</span> <br /> <span class=SpellE>Bromophenol</span> Blue Solution:</span></b><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'> <br /> <span class=SpellE>Dissovle</span> 0.1 g of <span class=SpellE><i>bromophenol</i></span><i> <br /> blue </i>with gentle heating in 1.5 ml of 0.1 M <i>sodium hydroxide </i>and 20<br /> ml of <i>ethanol </i>(95 <i>per cent)</i> and add sufficient <i>water </i>to<br /> produce 100 ml.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Complies<br /> with the following test.</span></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>SENSITIVITY- A <span class=SpellE>mlxture</span> of 0.05 ml of the solution and 20 ml of <i>carbon<br /> dioxide-free water </i>to which 0.05 ml of <i>0.1 M</i> <i>hydrochloric acid </i>has<br /> been added is yellow. Not more than 0.1 ml of <i>0.1 M sodium hydroxide </i>is<br /> required to change the <span class=SpellE>colour</span> to bluish violet.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=SpellE><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'>Bromophenol</span></b></span><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'> Blue Reagent:</span></b><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'> <br /> Dissolve 50 mg of <span class=SpellE><i>bromophenol</i></span><i> blue </i>with<br /> gentle heating in 3.73 ml of <i>0.02 M sodium hydroxide </i>and dilute to 100<br /> ml with <i>water.</i></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=SpellE><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'>Bromothymol</span></b></span><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'> Blue; 4<span class=GramE>,4'</span> <br /> <i>-(3H-2, </i>I-Benzoxathiol-3-ylidene)<span class=SpellE>bis</span>(</span></b><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family: "Times New Roman"'>2-bromothymol) S<span class=GramE>,S</span>-dioxide:</span></b><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'> <br /> C<sub>27</sub>H<sub>28</sub>Br<sub>2</sub>O<sub>5</sub>S=624.39.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=SpellE><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family: "Times New Roman"'>Crearn-coloured</span></span></span><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'> <br /> powder.</span></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=SpellE><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'>Bromothymol</span></b></span><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'> Blue Solution; Aqueous <span class=SpellE>Bromothymol</span> Blue Solution:</span></b><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'> <br /> Dissolve 50 mg of <span class=SpellE><i>bromothymol</i></span><i> blue </i>in 4<br /> ml of <i>0.02</i><b style='mso-bidi-font-weight:normal'> </b><i>M sodium<br /> hydroxide </i>and 20 ml of <i>ethanol </i>(95 <i>per cent). </i>After<b style='mso-bidi-font-weight:normal'> </b>solution is <span class=GramE>effected</span>,<br /> add sufficient <i>water </i>to produce 100 ml.</span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Complies<br /> with the following test.</span></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>SENSITIVITY - <span class=GramE>A</span> <span class=SpellE>mlxture</span> of 0.3 ml of the<br /> solution and 100 ml of <i>carbon dioxide- free water </i>is yellow. Not more<br /> than 0.1 ml of <i>0.02 M sodium hydroxide </i>is required to change the <span class=SpellE>colour</span> to blue.</span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=SpellE><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'>Calcon</span></b></span><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'>; CI 15705; <span class=SpellE>SolochromeDarkBlue</span>;<br /> Mordant Black 17; Sodium 2-hydroxy-l-(2-hydroxy-I-<span class=GramE>naphthylazo<br /> )</span>-naphthalene4- <span class=SpellE>sulphonate</span>:</span></b><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'> <br /> C<sub>20</sub>H<sub>13</sub>N<sub>2</sub>NaO<sub>5</sub>S=416.38</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>General<br /> laboratory reagent grade of commerce.</span></span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Brownish<br /> black powder with a violet sheen.</span></span><span style='font-size:9.0pt; font-family:Arial;mso-bidi-font-family:"Times New Roman"'> <span class=GramE>Gives<br /> a <span class=SpellE>purplered</span> <span class=SpellE>colour</span> with<br /> calcium ions in alkaline solution.</span> When metal ions are absent, for<br /> example, in the presence of an excess of <span class=SpellE>disodium</span> <span class=SpellE>edetate</span>, the solution is blue.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=SpellE><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'>Calcon</span></b></span><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'> <span class=SpellE>Mlxture</span>:</span></b><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'> <br /> <span class=GramE>A</span> <span class=SpellE>mlxture</span> of 1 part of <span class=SpellE><i>calcon</i></span><i> </i>with 99 parts of freshly ignited <i>anhydrous<br /> sodium <span class=SpellE>sulphate</span>.</i></span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Complies<br /> with the following test.</span></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>SENSITIVITY –<br /> Dissolve 0.l gin 2.5 ml of <i>water. </i>To l ml of the solution add 50 ml of <i>water,<br /> </i>10 ml of 1 <i>M sodium hydroxide</i> and 1 ml of a 1 per cent w/v solution<br /> of <i>magnesium <span class=SpellE>sulphate</span>;</i> the solution is blue.<br /> Add 0.1 ml of a 0.15 per cent w/v solution of <i>calcium chloride; </i>the<br /> solution becomes violet and on subsequent addition of 0.1 ml of <i>0.01 M <span class=SpellE>disodium</span> edentate</i> turns to blue again.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family: "Times New Roman"'>Congo Red; CI 22120; <span class=SpellE>Disodium</span> (4<span class=GramE>,4'</span> -<span class=SpellE>bipheny</span> Ibis- 2,2-azo) <span class=SpellE>bis</span>(1-amlnonaphthalene-4-sulphonate):</span></b><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'> <br /> C<sub>32</sub>H<sub>22</sub>N<sub>6</sub>Na<sub>2</sub>O<sub>6</sub>S<sub>2</sub>=<br /> 696.66</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Dark<br /> red or reddish brown powder.</span></span><span style='font-size:9.0pt; font-family:Arial;mso-bidi-font-family:"Times New Roman"'> <span class=GramE>Decomposes<br /> on exposure to acid fumes.</span></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family: "Times New Roman"'>Congo <span class=GramE>Red</span> Fibrin:</span></b><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'> <br /> Soak washed and shredded <i>fibrin </i><span class=SpellE>ovemlght</span> in a<br /> 2 per cent w/v solution of <span class=SpellE><i>congo</i></span><i> red </i>in<br /> <i>ethanol (90 per</i> <i>cent), </i>strain, wash the product with <i>water </i>and<br /> store under <i>ether.</i></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family: "Times New Roman"'>Cresol Red; 4<span class=GramE>,4'</span> <i>-(3H-2, </i>1-Benzoxathiol-<br /> 3-ylidene) <span class=SpellE>di</span>-o-cresol S,S-dioxide:</span></b><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'> <br /> C<sub>21</sub>H<sub>I8</sub>O<sub>5</sub>S=382.44</span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Red<br /> brown powder.</span></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family: "Times New Roman"'>Cresol Red Solution:</span></b><span style='font-size:9.0pt; font-family:Arial;mso-bidi-font-family:"Times New Roman"'> Warm 0.1 g of <i>cresol<br /> red </i>in a <span class=SpellE>mlxture</span> of 2.65 ml of <i>0.1 M sodium<br /> hydroxide </i>and 20 ml of <i>ethanol</i> <i>(95 per cent). </i>After solution<br /> is <span class=GramE>effected</span>, add sufficient <i>water</i> to produce<br /> 100 ml.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Complies<br /> with the following test.</span></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>SENSITIVITY - <span class=GramE>A</span> <span class=SpellE>mlxture</span> of 0.1 ml of the<br /> solution and 100 ml of <i>carbon dioxide-free water </i>to which 0.15 ml of <i>0.02<br /> M sodium</i> <i>hydroxide </i>has been added is purplish red. Not more than 0.1<br /> 5 ml of <i>0.02 M hydrochloric acid </i>is required to change the <span class=SpellE>colour</span> to yellow.</span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family: "Times New Roman"'>Crystal Violet; CI 42555; Basic Violet 3; <span class=SpellE>Hexamethylp-rosaniline</span> Chloride:</span></b><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'> <br /> C<sub>25</sub>H<sub>30</sub>CIN<sub>3</sub>= 407.98</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>When used for<br /> titrations in non-aqueous media, changes from violet (basic) through blue-green<br /> (neutral) to yellowish green (acidic).</span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family: "Times New Roman"'>Crystal Violet Solution:</span></b><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'> A 0.5 per cent<br /> w/v solution of <i>crystal violet </i>in <i>anhydrous glacial acetic acid.</i></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Complies<br /> with the following test.</span></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>SENSITIVITY - <span class=GramE>A</span> <span class=SpellE>mlxture</span> of 0.1 ml of the<br /> solution and 50 ml of <i>anhydrous glacial acetic acid </i>is bluish purple.<br /> Add 0.1 ml of <i>0.1 M <span class=SpellE>perchloric</span> acid; </i>the<br /> solution turns blue-green.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=SpellE><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'>Dimethyl</span></b></span><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'> Yellow; CI 11020;<br /> 4-Dimethylamlnoazobenzene: </span></b><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'>C<sub>I4</sub>H<sub>I5</sub>N<sub>3</sub>=<br /> 225.29</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Yellow<br /> crystalline leaflets; mp, about I16°.</span></span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Complies<br /> with the following test.</span></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>HOMOGENEITY -<br /> Carry out the method for <i>thin-layer <span class=SpellE>chromatorgraphy</span></i>,<br /> using <i>silica gel </i>G as the coating<i> </i><span class=SpellE>susbtance</span> <br /> and <i>dichloromethane </i>as the mobile phase. Apply<i> </i>to the plate 10 µl<br /> of a 0.01 per cent w/v solution in <i>dichloromethane.</i></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>The<br /> chromatogram shows only one spot.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=SpellE><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'>Dimethyl</span></b></span><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'> Yellow Solution:</span></b><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'> <br /> A 0.2 per cent w/v solution of <span class=SpellE><i>dimethyl</i></span><i> <br /> yellow </i>in <i>ethanol (90 per cent).</i></span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Complies<br /> with the following test.</span></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>SENSITIVITY - A<br /> solution containing 2 g of <i>ammonium chloride </i>in 25 ml of <i>carbon<br /> dioxide-free water, </i>to which is<i> </i>added 0.1 ml of the <span class=SpellE><i>dimethyl</i></span><i> yellow solution, </i>is yellow. Not<i> </i>more<br /> than 0.1 ml of <i>0.1 M hydrochloric acid </i>is required to<i> </i>change the <span class=SpellE>colour</span> to red.</span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=SpellE><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'>Dimethyl</span></b></span><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'> Yellow-<span class=SpellE>Oracet</span> <br /> Blue B Solution; <span class=SpellE>Dimethyl</span> <span class=SpellE>YellowSolvent</span> <br /> Blue 19 Solution:</span></b><span style='font-size:9.0pt;font-family:Arial; mso-bidi-font-family:"Times New Roman"'> Dissolve 15 mg of <span class=SpellE><i>dimethyl</i></span><i> <br /> yellow</i><b style='mso-bidi-font-weight:normal'> </b>and 15 mg of <span class=SpellE><i>oracet</i></span><i> blue B </i>in <i>chloroform </i>and dilute<br /> to 500 ml<b style='mso-bidi-font-weight:normal'> </b>with <i>chloroform.</i></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Eosin; CI<br /> 45380; Acid red 87: C<sub>20</sub>H<sub>6</sub>Br<sub>4</sub>Na<sub>2</sub>O<sub>5</sub>=<br /> 691.86</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>General<br /> laboratory reagent grade of commerce.</span></span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Red<br /> powder.</span></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family: "Times New Roman"'>Eosin Solution:</span></b><span style='font-size:9.0pt; font-family:Arial;mso-bidi-font-family:"Times New Roman"'> A 0.5 per cent w/v<br /> solution of <i>eosin </i>in <i>water.</i></span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=SpellE><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'>Eriochrome</span></b></span><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'> Black T; CI 14645; Mordant Black<br /> 11<span class=GramE>;SolochromeBlack</span>; Sodium 1-(l-hydroxy-2-naphthylazo<br /> )-5-nitro-2naphthol-4-sulphonate:</span></b><span style='font-size:9.0pt; font-family:Arial;mso-bidi-font-family:"Times New Roman"'> C<sub>20</sub>H<sub>I2</sub>N<sub>3</sub>NaO<sub>7</sub>S=<br /> 461.38</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>General<br /> laboratory reagent grade of commerce.</span></span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Brownish<br /> black powder having a faint, metallic sheen.</span></span><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'> <br /> <span class=GramE>Gives a red <span class=SpellE>colour</span> with calcium,<br /> magnesium, zinc and certain other metals in alkaline solutions.</span> When<br /> metal ions are absent, for example in the presence of an excess of <span class=SpellE>disodium</span> <span class=SpellE>edetate</span>, the solution is<br /> blue.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Store protected<br /> from light and moisture.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Complies<br /> with the following test.</span></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>SENSITIVITY -<br /> To 10 ml of a 1 in 200,000 solution in <span class=GramE>a</span> <span class=SpellE>mlxture</span> of equal parts of <i>methanol </i>and <i>water </i>add<br /> a 1 per cent w/v solution of <i>sodium hydroxide </i>until the pH is 10; the<br /> solution is pure blue in <span class=SpellE>colour</span> and free from<br /> cloudiness. Add 0.01 ml of <i>0.05 M magnesium <span class=SpellE>sulphate</span>;<br /> </i>the <span class=SpellE>colour</span> of the solution changes to red-violet,<br /> and on adding more <i>0.05 M magnesium</i> <span class=SpellE><i>sulphate</i></span><i>,<br /> </i>the solution becomes wine-red in <span class=SpellE>colour</span>.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=SpellE><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'>Eriochrome</span></b></span><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'> Black T <span class=SpellE>Mlxture</span>;<br /> <span class=SpellE>Eriochrome</span> Black T Triturate; Mordant Black 11 <span class=SpellE>Mlxture</span>:</span></b><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'> <span class=GramE>A</span> <span class=SpellE>mlxture</span> of 1 part of <span class=SpellE><i>eriochrome</i></span><b style='mso-bidi-font-weight:normal'> </b><i>black T </i>and 99 parts of <i>sodium<br /> chloride.</i></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Store protected<br /> from light and moisture.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Complies<br /> with the following test.</span></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>SENSITIVITY -<br /> Dissolve 50 mg <span class=GramE>in ]</span> 00 ml of <i>water, </i>a brownish<br /> violet <span class=SpellE>colour</span> is produced. Add 0.3 ml of 6 <i>M<br /> ammonia; </i>the <span class=SpellE>colour</span> changes to blue. Add 0.1 ml<br /> of a 1 per cent w/v solution of <i>magnesium <span class=SpellE>sulphate</span>;<br /> </i>the <span class=SpellE>colour</span> changes to violet.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=SpellE><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'>Eriochrome</span></b></span><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'> Black T Solution; Mordant Black<br /> 11 <span class=SpellE>Soluton</span>:</span></b><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Dissolve 0.2 g<br /> of <span class=SpellE><i>eriochrome</i></span><i> black T </i>and 2 g of <span class=SpellE><i>hydroxylamlne</i></span><i> hydrochloride </i>in sufficient <i>methanol<br /> </i>to produce 50 m\.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Prepare<br /> immediately before use.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family: "Times New Roman"'>Fast Blue B Salt; CI 37235:</span></b><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'> <br /> C<sub>I4</sub>H<sub>l2</sub>Cl<sub>2</sub>N<sub>4</sub>O<sub>2</sub>= 339.18</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>General<br /> laboratory reagent grade of commerce.</span></span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Dark<br /> green powder, <span class=SpellE>stabilised</span> by the addition of zinc<br /> chloride.</span></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Store protected<br /> from moisture in a cold place.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=SpellE><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'>Ferroin</span></b></span><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'> Solution; <span class=SpellE>Ferroin</span> <br /> <span class=SpellE>Sulphate</span> Solution; <span class=SpellE>Tris</span>-(l,<br /> 10phenanthroline) ferrous <span class=SpellE>Sulphate</span> Complex:</span></b><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'> <br /> Dissolve 0.7 g of <i>ferrous <span class=SpellE>sulphate</span> </i>and 1.5 g<br /> of 1<span class=GramE>,1</span> <i>O-<span class=SpellE>phenanthroline</span></i> <br /> <i>hydrochloride </i>in 70 ml of <i>water </i>and add sufficient <i>water </i>to<br /> produce 100 ml.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Complies<br /> with the following test.</span></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>SENSITIVITY -<br /> Add 0.1 ml of the solution and 0.15 ml of <span class=SpellE><i>osmlc</i></span><i> <br /> acid solution </i>to 50 ml of 1 <i>M <span class=SpellE>sulphuric</span> acid. </i>Add<br /> 0.1 ml of<i> 0.1 M eerie ammonium nitrate; </i>the <span class=SpellE>colour</span> <br /> changes from red<i> </i>to light blue.</span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=SpellE><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'>Indophenol</span></b></span><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'> Blue; CI49700:</span></b><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'> <br /> C<sub>I8</sub>H<sub>26</sub>N<sub>2</sub>O=276.34</span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>General<br /> laboratory reagent grade of commerce.</span></span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Dark<br /> purple powder.</span></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Complies<br /> with the following test.</span></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>HOMOGENEITY -<br /> Carry out the method for <i>thin-layer chromatography </i>(2.4.17), using <i>silica<br /> gel </i>G as the coating<i> </i>substance and <i>dichloromethane </i>as the<br /> mobile phase. Apply<i> </i>to the plate 10 /11 of a 0.0 I per cent w/v solution<br /> in<i> dichloromethane. </i>After removal of the plate, allow it to dry in<i> </i>air.<br /> The chromatogram shows only one spot, but a stain may<i> </i>remain at the<br /> point of origin.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family: "Times New Roman"'>Litmus:</span></b><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'> Fragments of blue pigment<br /> prepared from various species of <span class=SpellE><i>Rocella</i></span><i>, <span class=SpellE>Lecanora</span> </i>or other lichens. It has a characteristic <span class=SpellE>odour</span>. <span class=GramE>Partly soluble in <i>water </i>and<br /> in <i>ethanol.</i></span></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><i><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>NOTE<br /> </span></i><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family: "Times New Roman"'>- <i>Litmus is unsuitable for <span class=SpellE>determlning</span> <br /> the pH of alkaloids, carbonates and bicarbonates.</i></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family: "Times New Roman"'>Litmus Solution:</span></b><span style='font-size:9.0pt; font-family:Arial;mso-bidi-font-family:"Times New Roman"'> Boil 25 g of<br /> coarsely powdered <i>litmus </i>with 100 ml of <i>ethanol (90 per cent) </i>under<br /> a reflux condenser for 1 hour and discard the clear liquid. Repeat this<br /> operation with two quantities, each of 75 ml of <i>ethanol (90 per cent). </i>Digest<br /> the extracted litmus with 250 ml of <i>water </i>and filter.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=SpellE><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'>Metacresol</span></b></span><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'> Purple; 4<span class=GramE>,4'</span> <br /> <i>-(3H-2, </i>I-Benzoxanthiol-3-ylidene)-dim- cresol S,S-dioxide:</span></b><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'> <br /> C<sub>21</sub>H<sub>16</sub>O<sub>5</sub>S= 380.40</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>General<br /> laboratory reagent grade of commerce.</span></span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=SpellE><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'>Metalphthalein</span></b></span><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'>; <span class=SpellE>Phthalein</span> <br /> Purple:</span></b><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family: "Times New Roman"'> C<sub>32</sub>H<sub>32</sub>N<sub>2</sub>O<sub>12</sub>+aq</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Creamy<br /> white brown powder.</span></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Complies<br /> with the following test.</span></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>SENSITIVITY -<br /> Dissolve 10 mg in 1 ml of <i>strong ammonia solution </i>and dilute to <span class=SpellE>lOaml</span> with <i>water. </i>To 5 ml of the solution<i> </i>add<br /> 95 ml of <i>water, </i>4 ml of <i>strong ammonia solution, </i>50 ml of<i> <br /> ethanol </i>(95 <i>per cent) </i>and 0.2 ml of <i>0.1 M barium chloride; </i>the<br /> solution is bluish violet. Add 0.24 ml of <i>0.05 M <span class=SpellE>disodium</span> <br /> <span class=SpellE>edetate</span>; </i>the solution becomes <span class=SpellE>colourless</span>.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=SpellE><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'>Metanil</span></b></span><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'> Yellow; CI 13065; Sodium<br /> 4-anilinoazobenzene-3sulphonate:</span></b><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>C<sub>18</sub>H<sub>14</sub>N<sub>3</sub>NaO<sub>3</sub>S<br /> = 375.40</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Brownish yellow<br /> powder; soluble in <i>water </i>and in <i>ethanol; </i>slightly soluble in <i>acetone<br /> </i>and in <i>ether.</i></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=SpellE><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'>Metanil</span></b></span><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'> Yellow Solution:</span></b><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'> <br /> A 0.1 per cent w/v solution of <span class=SpellE><i>metanil</i></span><i> <br /> yellow </i>in <i>methanol.</i></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Complies<br /> with the following test.</span></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>SENSITIVITY -<br /> Add 0.1 ml of the solution to 50 ml of <i>anhydrous glacial acetic acid; </i>the<br /> <span class=SpellE>mlxture</span> is pinkish red.</span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Add 0.05 ml of <i>0.1<br /> M <span class=SpellE>perchloric</span> acid; </i>the <span class=SpellE>colour</span> <br /> changes to violet.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family: "Times New Roman"'>Methyl Orange; CI 13025; Sodium 4-dimethylamlnoazobenzene-<br /> 4-sulphonate:</span></b><span style='font-size:9.0pt;font-family:Arial; mso-bidi-font-family:"Times New Roman"'> C<sub>14</sub>H<sub>14</sub>N<sub>3</sub>NaO<sub>3</sub>S<br /> = 327.34</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Orange-yellow<br /> powder or crystalline scales; <span class=GramE>Sparingly</span> soluble in hot<br /> <i>water; </i>slightly soluble in <i>water; </i>practically insoluble in <i>ethanol.</i></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family: "Times New Roman"'>Methyl Orange Solution:</span></b><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'> Dissolve 0.1 g<br /> of <i>methyl orange </i>in 80 ml of <i>water </i>and add sufficient <i>ethanol </i>(95<br /> <i>per cent) </i>to produce l00 ml.</span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Complies<br /> with the following test.</span></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>SENSITIVITY - <span class=GramE>A</span> <span class=SpellE>mlxture</span> of 0.1 m] of the<br /> solution and 100 ml of <i>carbon dioxide-free water </i>is yellow. Not more<br /> than 0.1 ml of <i>0.1 M hydrochloric acid </i>is required to change the <span class=SpellE>colour</span> to red.</span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family: "Times New Roman"'>Methyl Red; CI 13020; 2-(4-<span class=GramE>Dimethylarninophenylazo<br /> )</span>-benzoic Acid:</span></b><span style='font-size:9.0pt;font-family:Arial; mso-bidi-font-family:"Times New Roman"'> C<sub>15</sub>H<sub>15</sub>N<sub>3</sub>O<sub>2</sub>=269.30</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Dark<br /> red powder or violet crystals; mp, about 182°; soluble in <i>ethanol; </i>practically<br /> insoluble in <i>water.</i></span></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family: "Times New Roman"'>Methyl Red- <span class=SpellE>Methylene</span> Blue<br /> Solution; Methyl Red <span class=SpellE>Mlxed</span> Solution:</span></b><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'> <br /> Dissolve 0.1 g of <i>methyl red </i>and 50 mg of <span class=SpellE><i>methylene</i></span><b style='mso-bidi-font-weight:normal'> </b><i>blue </i>in 100 ml of <i>ethanol </i>(95<br /> <i>per cent). </i><span class=SpellE>Colour</span> changes from<b style='mso-bidi-font-weight:normal'> </b>reddish violet to green (pH range, 5.2<br /> to 5.6).</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family: "Times New Roman"'>Methyl Red Solution:</span></b><span style='font-size:9.0pt; font-family:Arial;mso-bidi-font-family:"Times New Roman"'> Dissolve 50 mg of <i>methyl<br /> red </i>in a <span class=SpellE>mlxture</span> of 1.86 ml of <i>0.1 M sodium<br /> hydroxide </i>and 50 ml of <i>ethanol</i> <i>(95 per cent). </i>After solution<br /> is <span class=GramE>effected</span>, add sufficient <i>water</i> to produce<br /> 100 ml.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Complies<br /> with the following test.</span></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>SENSITIVITY - <span class=GramE>A</span> <span class=SpellE>mlxture</span> of 0.1 ml of the<br /> solution, 100 ml of <i>carbon dioxide-free water </i>and 0.05 ml of <i>0.02 M<br /> hydrochloric</i> <i>acid </i>is red. Not more than 0.1 ml of <i>0.02 M sodium<br /> hydroxide</i> is required to change the <span class=SpellE>colour</span> to<br /> yellow.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=SpellE><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'>Methylenebisacrylamlde</span></b></span><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'>:</span></b><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'> <br /> C<sub>7</sub>H<sub>10</sub>N<sub>2</sub>O<sub>2</sub> = 154.2</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>A<br /> fine, white or almost white powder, slightly soluble in <i>water, </i>soluble<br /> in <i>alcohol.</i></span></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>mp</span></span><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>.<br /> <span class=GramE>it</span> melts with decomposition at a temperature above<br /> 300°.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=SpellE><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'>Methylene</span></b></span><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'> Blue; CI 52015; Basic Blue 9; 3<span class=GramE>,7</span>-Bis-(<span class=SpellE>dimethylamlno</span>)<span class=SpellE>phenothiazin</span>- 5-ium chloride:</span></b><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>C<sub>16</sub>H<sub>18</sub>CIN<sub>3</sub>S.xH<sub>2</sub>0<br /> = 319.86 (anhydrous)</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=SpellE><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family: "Times New Roman"'>Redox</span></span></span><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'> <br /> indicator grade suitable for biological work.</span></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Dark<br /> green or brown crystals with bronze <span class=SpellE>lustre</span> or<br /> crystalline powder; hygroscopic; soluble in <i>water </i>and in <i>chloroform;</i> <br /> sparingly soluble in <i>ethanol; </i>insoluble in <i>ether.</i></span></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=SpellE><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'>Methylene</span></b></span><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'> Blue Solution:</span></b><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'> <br /> Dissolve 150 mg of <span class=SpellE><i>methylene</i></span><i> blue </i>in<br /> 100 ml of <i>ethanol </i>(95 <i>per cent) </i>and dilute with <i>ethanol (95<br /> per cent) </i>to produce 250 ml.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family: "Times New Roman"'>Methyl Orange-<span class=SpellE>Xylene</span> <span class=SpellE>Cyanol</span> FF Solution:</span></b><span style='font-size:9.0pt; font-family:Arial;mso-bidi-font-family:"Times New Roman"'> Dissolve 0.1 g of <i>methyl<br /> orange </i>and 0.26 g of <span class=SpellE><i>xylene</i></span><i> <span class=SpellE>cyanol</span> FF </i>in 50 ml of <i>ethanol </i>(95 <i>per cent) </i>and<br /> add sufficient <i>water </i>to produce l00ml.</span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family: "Times New Roman"'>Methyl <span class=SpellE>Thymol</span> Blue; [3H-2<span class=GramE>,1</span>-Benzoxathiol-3-ylidenebis(6-hydroxy- 5-isopropyl-<br /> 2-methyl-m-pheny <span class=SpellE>lene</span>) <span class=SpellE>methy</span> <br /> <span class=SpellE>lenenitrilo</span>]<span class=SpellE>tetraacetic</span> <br /> acid S, S-dioxide <span class=SpellE>Tetrasodium</span> salt:</span></b><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>C<sub>37</sub>H<sub>40</sub>N<sub>2</sub>Na<sub>4</sub>O<sub>13</sub>S<br /> = 844.75</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>General<br /> laboratory reagent grade of commerce.</span></span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Produces<br /> a blue <span class=SpellE>colour</span> with calcium ions in alkaline solution.</span></span><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'> <br /> When metal ions are absent, for example, in the presence of an excess of <span class=SpellE>disodium</span> <span class=SpellE>edetate</span>, the solution is<br /> grey.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family: "Times New Roman"'>1-Naphtholbenzein; a-<span class=SpellE>Naphtholphthalein</span>;<br /> <span class=SpellE>Phenylbis</span>-(4hydroxynaphthyl<span class=GramE>)methenol:<span style='font-weight:normal'>C<sub>27</sub>H<sub>20</sub>O<sub>3</sub></span></span></span></b><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'> <br /> = 392.50</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'>Brownish red powder or shiny<br /> brownish black crystals.</span></b></span><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'> <br /> 1-Naphtholbenzein Solution; a-<span class=SpellE>Naphtholbenzein</span> <br /> Solution: </span></b><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family: "Times New Roman"'>A 0.2 per cent w/v solution of <i>1-naphtholbenzein </i>in<b style='mso-bidi-font-weight:normal'> </b><i>anhydrous glacial acetic acid.</i></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Complies<br /> with the following test.</span></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>SENSITIVITY -<br /> Add 0.25 ml to 50 ml of <i>anhydrous glacial acetic acid. </i>Not more than<br /> 0.05 ml of 0.1 <i>M <span class=SpellE>perchloric</span> acid </i>is<i> </i>required<br /> to change the <span class=SpellE>colour</span> of the solution from brownish<i> <br /> </i>yellow to green.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family: "Times New Roman"'>Neutral Red; CI 50040; Basic Red 5;<br /> 3-Amlno-7-dimethylamlno2-methylphenazine <span class=SpellE>Monohydrochloride</span>:</span></b><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'> <br /> C<sub>15</sub>H<sub>l6</sub>N<sub>4</sub>.HCI = 288.78</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Reddish to<br /> olive green coarse powder; sparingly soluble in <i>ethanol </i>and in <i>water.</i></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family: "Times New Roman"'>Neutral Red Solution:</span></b><span style='font-size:9.0pt; font-family:Arial;mso-bidi-font-family:"Times New Roman"'> A 0.1 per cent w/v<br /> solution of <i>neutral red </i>in <i>ethanol </i>(50 <i>per cent).</i></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family: "Times New Roman"'>Nile Blue A; CI 51180; 5-Amlno-9-diethylamlnobenzo<span class=GramE>[ a</span>]<span class=SpellE>phenoxazinylium</span> Hydrogen <span class=SpellE>Sulphate</span>:</span></b><span style='font-size:9.0pt; font-family:Arial;mso-bidi-font-family:"Times New Roman"'> C<sub>20</sub>H<sub>21</sub>N<sub>3</sub>O<sub>5</sub>S=415.47</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=SpellE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Green<span class=GramE>,crystalline</span></span></span><span style='font-size:9.0pt; font-family:Arial;mso-bidi-font-family:"Times New Roman"'> powder with a bronze<br /> <span class=SpellE>lustre</span>.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Complies<br /> with the following test.</span></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>LIGHT<br /> ABSORBTION - A 0.0005 per cent w/v solution in <i>ethanol </i>(50 <i>per cent) </i>exhibits<br /> a maximum at about 640 nm.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family: "Times New Roman"'>Nile Blue A Solution:</span></b><span style='font-size:9.0pt; font-family:Arial;mso-bidi-font-family:"Times New Roman"'> A 1 per cent w/v<br /> solution of <span class=SpellE><span class=GramE><i>nile</i></span></span><i> <br /> blue A </i>in <i>anhydrous glacial acetic acid.</i></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Complies<br /> with the following test.</span></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>SENSITIVITY - A<br /> solution containing 0.25 ml in 50 ml of <i>anhydrous glacial acetic acid </i>is<br /> blue. Not more than 0.1 ml of <i>0.1 M <span class=SpellE>perchloric</span> <br /> acid </i>is required to change the <span class=SpellE>colour</span> of the<br /> solution to bluish green.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=SpellE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Colour</span></span><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'> <br /> changes from blue to red (pH range, 9.0 to 13.0).</span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=SpellE><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'>Oracet</span></b></span><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'> Blue B; Solvent Blue 19:</span></b><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'> <br /> <span class=GramE>A</span> <span class=SpellE>mlxture</span> of<br /> 1-methylamlno4-anilinoanthraquinone, C<sub>21</sub>H<sub>16</sub>N<sub>2</sub>O<sub>2</sub>,<br /> and l-amlno-4anilinoanthraq <span class=SpellE>uinone</span>, C<sub>20</sub>H<sub>14</sub>N<sub>2</sub>O<sub>2</sub>.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>When used for<br /> titration in non-aqueous media, it changes from blue (basic) through purple<br /> (neutral) to pink (acidic).</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=SpellE><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'>Oracet</span></b></span><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'> Blue B Solution:</span></b><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'> <br /> A 0.5 per cent w/v solution of <span class=SpellE><i>oracet</i></span><i> blue<br /> B </i>in <i>anhydrous glacial acetic acid.</i></span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family: "Times New Roman"'>Phenol Red; <span class=SpellE>Phenolsulphonphthalein</span>;<br /> 4<span class=GramE>,4'</span> <i>-(3H-2,1</i>Benzoxathiol-3-ylidene )<span class=SpellE>diphenol</span> S,S-dioxide:</span></b><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>C<sub>19</sub>H<sub>I4</sub>O<sub>5</sub>S=<br /> 354.39</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Bright to dark<br /> red crystalline powder; freely soluble in solutions of alkali carbonates and<br /> hydroxides; slightly soluble in <i>ethanol </i>(95 <i>per cent); </i>very<br /> slightly soluble in <i>water.</i></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family: "Times New Roman"'>Phenol Red Solution:</span></b><span style='font-size:9.0pt; font-family:Arial;mso-bidi-font-family:"Times New Roman"'> Dissolve 0.1 g of <i>phenol<br /> red </i>in 2.82 ml of 0.1 <i>M sodium hydroxide </i>and 20 ml of <i>ethanol </i>(95<br /> <i>per</i> <i>cent). </i>After solution is <span class=GramE>effected</span>,<br /> add sufficient <i>water </i>to produce l00 ml.</span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Complies<br /> with the following test.</span></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>SENSITIVITY - <span class=GramE>A</span> <span class=SpellE>mlxture</span> of 0.1 ml of the<br /> solution and 100 ml of <i>carbon dioxide-free water </i>is yellow. Not more<br /> than 0.1 ml of 0.02 <i>M sodium hydroxide </i>is required to change the <span class=SpellE>colour</span> of the solution to reddish violet.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family: "Times New Roman"'>Phenol Red Reagent:</span></b><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>SOLUTION I -<br /> Dissolve 33 mg of <i>phenol red </i>in 1.5 ml of 2 <i>M sodium hydroxide </i>and<br /> dilute to 100 ml with <i>water.</i></span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>SOLUTION n -<br /> Dissolve 25 mg of <i>ammonium <span class=SpellE>sulphate</span> </i>in 235 ml<br /> of <i>water, </i>add 105 ml of 2 <i>M sodium hydroxide </i>and 135 ml of 2 <i>M<br /> acetic acid.</i></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Add 25 ml of<br /> solution I to solution II. If necessary, adjust the pH of the mixture to 4.7.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family: "Times New Roman"'>Phenolphthalein:</span></b><span style='font-size:9.0pt; font-family:Arial;mso-bidi-font-family:"Times New Roman"'> Of the Indian<br /> Pharmacopoeia.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family: "Times New Roman"'>Phenolphthalein Solution:</span></b><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'> A 1.0 per cent<br /> w/v solution of <i>phenolphthalein </i>in <i>ethanol </i>(95 <i>per cent).</i></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family: "Times New Roman"'>Phenolphthalein Solution, Dilute:</span></b><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'> <br /> Dissolve 0.1 g of <i>phenolphthalein </i>in 80 ml of <i>ethanol </i>(95 <i>per<br /> cent) </i>and add sufficient <i>water </i>to produce 100 m<span class=GramE>!.</span></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Complies<br /> with the following test.</span></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>SENSITIVITY - <span class=GramE>A</span> <span class=SpellE>mlxture</span> of 0.1 ml of the<br /> solution and 100 ml of <i>carbon dioxide-free water </i>is <span class=SpellE>colourless</span>.<br /> Not more than 0.2 ml of 0.02 <i>M sodium hydroxide </i>is required to change<br /> the <span class=SpellE>colour</span> to pink.</span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family: "Times New Roman"'>Phenolphthalein-<span class=SpellE>Thymol</span> Blue<br /> Solution:</span></b><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family: "Times New Roman"'> Dissolve 0.1 g of <span class=SpellE><i>thymol</i></span><i> <br /> blue </i>in a mixture of 2.2 ml of 0.1 <i>M sodium hydroxide</i> and 50 ml of <i>ethanol<br /> </i>(95 <i>per cent) </i>and dilute to 100 ml with <i>water. </i><span class=GramE>Mix 3 volumes of this solution with 2 volumes of <i>phenolphthalein<br /> solution.</i></span></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=SpellE><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'>Pyridylazonaphthol</span></b></span><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'>; PAN; 1-(2-<span class=GramE>Pyridylazo<br /> )</span>-2-naphthol:</span></b><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>C<sub>15</sub>H<sub>11</sub>N<sub>3</sub>O=<br /> 249.27</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>General<br /> laboratory reagent grade of commerce.</span></span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Brick<br /> red or orange-red powder; mp, about 1400.</span></span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=SpellE><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'>Pyridylazonaphthol</span></b></span><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'> Solution:</span></b><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'> <br /> A 0.1 per cent w/v solution in <i>ethanol.</i></span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Complies<br /> with the following test.</span></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>SENSITIVITY -<br /> To 50 ml of <i>water </i>add 10 ml of <i>acetate buffer pH </i>4.4<span class=GramE>,0.1</span> ml of <i>0.02 M <span class=SpellE>disodium</span> <span class=SpellE>edetate</span> </i>and 0.25 ml of the<i> </i>reagent under <span class=SpellE>examlnation</span>; a yellow <span class=SpellE>colour</span> is<br /> produced. Add<i> </i>0.15 ml of a 0.5 per cent w/v solution of <i>cupric <span class=SpellE>sulphate</span>; </i>the<i> </i><span class=SpellE>colour</span> <br /> changes to violet.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=SpellE><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'>Quinaldine</span></b></span><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'> Red; 2-(4-Dimethylamlnostyryl) <span class=SpellE>quinoline</span> <span class=SpellE>Ethiodide</span>:</span></b><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'> <br /> C<sub>21</sub>H<sub>23</sub>IN<sub>2</sub>= 430.33</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>When used for<br /> the non-aqueous titration in <i>anhydrous glacial acetic acid, </i>the <span class=SpellE>colour</span> changes from magenta (basic) to almost<i> </i><span class=SpellE>colourless</span> (acidic).</span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=SpellE><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'>Quinaldine</span></b></span><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'> Red Solution:</span></b><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'> <br /> A 0.1 per cent w/v solution of <span class=SpellE><i>quinaldine</i></span><i> <br /> red </i>in <i>methanol.</i></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family: "Times New Roman"'>Ruthenium Red; Ammoniated Ruthenium <span class=SpellE>Oxychloride</span>:<br /> </span></b><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family: "Times New Roman"'>H12Cl2N1402Ru3<span class=GramE>,4H20</span> = 858.42</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=SpellE><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family: "Times New Roman"'>Mlcroscopical</span></span></span><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'> <br /> staining grade of commerce.</span></span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Brownish<br /> red powder.</span></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family: "Times New Roman"'>Ruthenium Red Solution:</span></b><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'> Dissolve 8 mg<br /> of <i>ruthenium red </i>in</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>10<br /> ml of <i>lead acetate solution.</i></span></span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family: "Times New Roman"'>Sudan Red G; CI 12150; Sudan Red I;<br /> 1-(2'-Methoxyphenylazo)-2-naphthol;</span></b><span style='font-size:9.0pt; font-family:Arial;mso-bidi-font-family:"Times New Roman"'> C<sub>17</sub>H<sub>I4</sub>N<sub>4</sub>O=290.32</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Complies<br /> with the following test.</span></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>HOMOGENEITY -<br /> Carry out the method for <i>thin-layer chromatography</i>, using <i>silica gel </i>G<br /> as the coating<i> </i>substance and <i>dichloromethane </i>as the mobile phase<br /> but<i> </i>allowing the solvent front to ascend 10 cm above the line of<i> </i>application.<br /> Apply to the plate 10 <span class=SpellE>fll</span> of a 0.1 per cent w/v<i> </i>solution<br /> in <i>dichloromethane. </i>After removal of the plate, allow<i> </i>it to dry<br /> in air. The chromatogram shows only one spot.</span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=SpellE><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'>Thymol</span></b></span><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'> Blue; <span class=SpellE>Thymolsulphonphthalein</span>;<br /> 4<span class=GramE>,4'</span> <i>-(3H)-2, 1</i>Benzoxathiol-3-ylidene) <span class=SpellE>dithymol</span> S,S-dioxide:</span></b><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'> <span style='mso-bidi-font-style:italic'>C<sub>27</sub>H<sub>30</sub>O<sub>5</sub>S<i> <br /> =</i></span>466.60</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Brownish green,<br /> crystalline powder; soluble in <i>ethanol (95 per cent) </i>and in dilute<br /> alkali solutions; slightly soluble in<i> water.</i></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=SpellE><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'>Thymol</span></b></span><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'> Blue Solution:</span></b><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'> <br /> Dissolve 0.1 g of <span class=SpellE><i>thymol</i></span><i> blue </i>in 2.15<br /> ml of <i>0.1 M sodium hydroxide </i>and 20 ml of <i>ethanol</i> <i>(95 per<br /> cent). </i>After solution is <span class=GramE>effected</span>, add sufficient <i>water</i> <br /> to produce 100 ml.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Complies<br /> with the following test.</span></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>SENSITIVITY - <span class=GramE>A</span> <span class=SpellE>mlxture</span> of 0.1 ml <span class=SpellE>ofthe</span> solution and 100 ml of <i>carbon <span class=SpellE>dioxidejree</span> <br /> water </i>to which 0.2 ml of <i>0.02 M sodium</i> <i>hydroxide </i>has been<br /> added is blue. Not more than 0.1 ml of <i>0.02 M hydrochloric acid </i>is<br /> required to change the <span class=SpellE>colour</span> to yellow.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=SpellE><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'>Thymol</span></b></span><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'> Blue Solution, <span class=SpellE>Ethanolic</span>:</span></b><span style='font-size:9.0pt; font-family:Arial;mso-bidi-font-family:"Times New Roman"'> Dissolve 0.1 g of <span class=SpellE><i>thymol</i></span><i> blue </i>in 100 ml of <i>ethanol </i>(95 <i>per<br /> cent) </i>and filter, if necessary.</span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=SpellE><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'>Thymolphthalein</span></b></span><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'>; 3<span class=GramE>,3</span>-Bis(<br /> 4-hydroxy-5-isopropyl- 2mehtylphenyl)<span class=SpellE>phthalide</span>:</span></b><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'> <br /> C<sub>28</sub>H<sub>30</sub>O<sub>4</sub>=430.55</span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>White to<br /> slightly yellow crystalline powder; soluble in <i>ethanol (95 per cent) </i>and<br /> in solutions of alkali hydroxides; insoluble<i> </i>in <i>water.</i></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=SpellE><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'>Thymolphthalein</span></b></span><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'> Solution:</span></b><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'> <br /> A 0.1 per cent w/v solution of <span class=SpellE><i>thymolphthalein</i></span><i> <br /> </i>in <i>ethanol </i>(95 <i>per cent).</i></span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Complies<br /> with the following test.</span></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>SENSITIVITY - <span class=GramE>A</span> <span class=SpellE>mlxture</span> of 0.05 ml and 100 ml of<br /> <i>carbon dioxide-free water </i>is <span class=SpellE>colourless</span>. Not<br /> more than 0.05 ml of</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><i><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>0.1<br /> M sodium hydroxide </span></i><span style='font-size:9.0pt;font-family:Arial; mso-bidi-font-family:"Times New Roman"'>is required to change the <span class=SpellE>colour</span> to blue.</span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family: "Times New Roman"'>Titan Yellow; CI 19540; <span class=SpellE>Thiazol</span> <br /> Yellow; Sodium 2<span class=GramE>,2</span>[(<span class=SpellE>diazoamlno</span> <br /> )<span class=SpellE>di-p-phenylene</span>] <span class=SpellE>bis</span>(6-methylbenzothiazole-7sulphonate):<br /> </span></b><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family: "Times New Roman"'>C<sub>28</sub>H<sub>I9</sub>N<sub>5</sub>Na<sub>2</sub>O<sub>6</sub>S<sub>4</sub>=<br /> 695.71</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Yellowish<br /> brown powder.</span></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family: "Times New Roman"'>Titan Yellow Solution:</span></b><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'> A 0.05 per<br /> cent w/v solution of <i>titan yellow.</i></span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Complies<br /> with the following test.</span></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>SENSITIVITY -<br /> Add 0.1 ml to <span class=GramE>a</span> <span class=SpellE>mlxture</span> of<br /> 10ml of <i>water, </i>0.2 ml of a 0.0101 per cent w/v solution of <i>magnesium <span class=SpellE>sulphate</span> </i>and 1.0 ml of 1 <i>M sodium hydroxide; </i>a<br /> pink <span class=SpellE>colour</span> is produced.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=SpellE><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'>Xylene</span></b></span><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'> <span class=SpellE>Cyanol</span> <br /> FF:</span></b><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family: "Times New Roman"'> C142135</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Blue,<br /> ethanol-soluble dye used as a screening agent in <i>methyl orange-<span class=SpellE>xylene</span> <span class=SpellE>cyanol</span> FF solution.</i></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=SpellE><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'>Xylenol</span></b></span><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'> Orange; [3H-2<span class=GramE>,1</span>-Benzoxathiol-3-ylidenebis-(6hydroxy-<br /> 5-methyl-m-pheny <span class=SpellE>lene</span> )<span class=SpellE>methylenenitrilo</span> <br /> ]tetra acetic acid S,S-dioxide <span class=SpellE>Tetrasodium</span> Salt:</span></b><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'> <br /> C<sub>3I</sub>H<sub>28</sub>N<sub>2</sub>NH<sub>2</sub>O<sub>I3</sub>S=760.60</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>General<br /> laboratory reagent grade of commerce.</span></span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Reddish brown,<br /> crystalline powder; gives a violet <span class=SpellE>colour</span> with<br /> mercury, lead, zinc and certain other metal ions, in alkaline solutions. When<br /> metal ions are absent, for example in the presence of an excess of <span class=SpellE>disodium</span> <span class=SpellE>edetate</span>, the solution is<br /> yellow.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=SpellE><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'>XylenolOrange</span></b></span><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'> <span class=SpellE>Mlxture</span>;<br /> <span class=SpellE>Xylenol</span> Orange Triturate:</span></b><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'> <br /> Triturate</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>1 part of <span class=SpellE><i>xylenol</i></span><i> orange </i>with 99 parts of <i>potassium<br /> nitrate.</i></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=GramE><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Complies<br /> with the following test.</span></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>SENSITIVITY -<br /> Add 50 mg to <span class=GramE>a</span> <span class=SpellE>mlxture</span> of 50<br /> ml of <i>water, </i>1 ml of 2 <i>M acetic acid </i>and 0.05 ml of <i>lead<br /> nitrate solution. </i>Add sufficient <span class=SpellE><i>hexamlne</i></span><i> <br /> </i>to change the <span class=SpellE>colour</span> from yellow to violet red.<br /> Add 0.1 ml of <i>0.1 M <span class=SpellE>disodium</span> <span class=SpellE>edetate</span>;<br /> </i>the <span class=SpellE>colour</span> changes to yellow.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=SpellE><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'>Xylenol</span></b></span><b style='mso-bidi-font-weight:normal'><span style='font-size:9.0pt;font-family: Arial;mso-bidi-font-family:"Times New Roman"'> Orange Solution:</span></b><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'> <br /> <span class=SpellE>Mlx</span> 0.1 g of <span class=SpellE><i>xylenol</i></span><i> <br /> orange </i>with 100 ml of <i>water </i>and filter, if <span class=SpellE>necessar</span></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><o:p> </o:p></p> <br /> </div> <br /> </body> <br /> <br /> </html> <div class="separator" style="clear: both; text-align: center;"><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEimL_lfDTiI3WPyrjSCVy5XyZekZT_aOGBHfFNJYHYrf4ZfxeY6OhoDqI0HH5W2ZGD0RRbbUJw2TOkr_AJmXriEjRpeZBldGA3f_OCwwbnSYPT15vD4MRMa71jPIQGZfi0PP0IFDVBW1cBV/s1600/image001.jpg" imageanchor="1" style="clear:left; float:left;margin-right:1em; margin-bottom:1em"><img border="0" height="320" width="178" src="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEimL_lfDTiI3WPyrjSCVy5XyZekZT_aOGBHfFNJYHYrf4ZfxeY6OhoDqI0HH5W2ZGD0RRbbUJw2TOkr_AJmXriEjRpeZBldGA3f_OCwwbnSYPT15vD4MRMa71jPIQGZfi0PP0IFDVBW1cBV/s320/image001.jpg" /></a></div>http://scholarpharma.blogspot.com/2012/01/preparation-of-indicator-solutions.html0margipatel02@gmail.com (margipatel02@gmail.com)tag:blogger.com,1999:blog-8563020669307343167.post-6178702340954113374Fri, 06 Jan 2012 03:40:00 +00002012-01-05T19:40:55.650-08:00Preparation of Standard SolutionsPreparation of Standard Solutions<html xmlns:v="urn:schemas-microsoft-com:vml" xmlns:o="urn:schemas-microsoft-com:office:office" xmlns:w="urn:schemas-microsoft-com:office:word" xmlns="http://www.w3.org/TR/REC-html40"> <br /> <br /> <head> <br /> <meta http-equiv=Content-Type content="text/html; charset=windows-1252"> <br /> <meta name=ProgId content=Word.Document> <br /> <meta name=Generator content="Microsoft Word 11"> <br /> <meta name=Originator content="Microsoft Word 11"> <br /> <link rel=File-List href="Preparation%20of%20Standard%20Solutions_files/filelist.xml"> <br /> <title>Preparation of Standard Solutions </title> <br />  <br /> <style>  </style> <br />  <br /> </head> <br /> <br /> <body lang=EN-US style='tab-interval:.5in'> <br /> <br /> <div class=Section1> <br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; mso-outline-level:3'><a name=3065956234078809843></a><b><span style='font-size: 13.5pt;mso-bidi-font-family:"Times New Roman"'>Preparation of Standard<br /> Solutions <o:p></o:p></span></b></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Acetaldehyde<br /> Standard Solution (100 <span class=SpellE>ppm</span> C<sub>2</sub>H<sub>4</sub>O):</span></b><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'> Dissolve 1.0<br /> g of <i>acetaldehyde </i>in sufficient <i>2-propanol </i>to produce 100ml and<br /> dilute 5.0ml of the solution to 500.0 ml with <i>2-propanol.</i></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=SpellE><b style='mso-bidi-font-weight:normal'><span style='font-family:Arial;mso-bidi-font-family: "Times New Roman"'>Alumlnium</span></b></span><b style='mso-bidi-font-weight: normal'><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'> <br /> Standard Solution (2 <span class=SpellE>ppm</span> Al):</span></b><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'> Dilute 2<br /> volumes of a 0.176 per cent w/v solution of <span class=SpellE><i>alumlnium</i></span><i> <br /> potassium <span class=SpellE>sulphate</span></i> in 0.1 M <span class=SpellE><i>sulphuric</i></span><i> <br /> acid </i>to 100 volumes with <i>water.</i></span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=SpellE><b style='mso-bidi-font-weight:normal'><span style='font-family:Arial;mso-bidi-font-family: "Times New Roman"'>Alumlnium</span></b></span><b style='mso-bidi-font-weight: normal'><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'> <br /> Standard Solution (10 <span class=SpellE>ppmAl</span>):</span></b><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'> Dilute 1<br /> volume of a 1.39 per cent w/v solution of <span class=SpellE><i>alumlnium</i></span><i> <br /> nitrate </i>to 100 volumes with <i>water.</i></span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Ammonium<br /> Standard Solution (1ppm NH<sub>4</sub>)<span class=GramE>:<span style='font-weight:normal'>Dilute</span></span></span></b><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'> 10.0ml of a<br /> 0.0741 % w/v solution of <i>ammonium chloride </i>to 25.0 ml with <i>ammonia-free<br /> water. </i>Dilute 1 volume of the resulting solution to 100 volumes with <i>ammonia-free<br /> water </i>immediately before use.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Arsenic<br /> Standard Solution (1 <span class=SpellE>ppm</span> As):</span></b><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'> Dilute J<br /> volume of <i>arsenic standard solution (10 <span class=SpellE>ppm</span> As) </i>to<br /> 10 volumes with <i>water.</i></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Arsenic<br /> Standard Solution (10 <span class=SpellE>ppm</span> <span class=GramE>As</span>):</span></b><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'> Dissolve 0.33<br /> g of <i>arsenic trioxide </i>in 5 ml of 2M <i>sodium hydroxide </i>and dilute<br /> to 250.0 ml with <i>water. </i>Dilute 1 volume of this solution to 100 volumes<br /> with <i>water.</i></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Barium<br /> Standard Solution (10 <span class=SpellE>ppm</span> <span class=SpellE>Ba</span>):</span></b><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'> Dilute 1.0 ml<br /> of a 0.178 per cent w/v solution of <i>barium chloride </i>to 100.0 ml with <i>water.</i></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=SpellE><b style='mso-bidi-font-weight:normal'><span style='font-family:Arial;mso-bidi-font-family: "Times New Roman"'>Cadmlum</span></b></span><b style='mso-bidi-font-weight: normal'><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'> <br /> Standard Solution (10 <span class=SpellE>ppm</span> <span class=SpellE>Cd</span>):</span></b><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'> Dilute 2.0 ml<br /> of a 0.228 per cent w/v solution of <span class=SpellE><i>cadmlum</i></span><i> <br /> <span class=SpellE>sulphate</span> </i>to 200.0 ml with <i>water.</i></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Calcium<br /> Standard Solution (10 <span class=SpellE>ppm</span> Ca):</span></b><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'> Dissolve<br /> 0.624 g of dried <i>calcium carbonate </i>in <i>distilled water </i>containing<br /> 3 ml of <i>5 M acetic acid </i>and dilute to 250.0 ml with <i>distilled water.</i> <br /> Dilute 1 volume of this solution to 100 volumes with <i>distilled</i> <i>water.</i></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Calcium<br /> Standard Solution (100 <span class=SpellE>ppm</span> Ca), <span class=SpellE>Ethanolic</span>:</span></b><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'> Dissolve 2.50<br /> g of dried <i>calcium carbonate </i>in 12 ml of 5 <i>M acetic acid</i> and<br /> dilute to 1000.0 ml with <i>distilled water. </i>Dilute 1 volume of this<br /> solution to 10 volumes with <i>ethanol </i>(95 per cent).</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Chloride<br /> Standard Solution (5 <span class=SpellE>ppm</span> <span class=SpellE>Cl</span>):</span></b><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'> Dilute<br /> 1volume of a 0.0824 per cent w/v solution of <i>sodium chloride </i>to 100<br /> volumes with <i>water.</i></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Chloride<br /> Standard Solution (25 <span class=SpellE>ppm</span> CI):</span></b><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'> Dilute 5<br /> volumes of a 0.0824 per cent w/v solution of <i>sodium chloride </i>to 100<br /> volumes with <i>water.</i></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Copper<br /> Standard Solution:</span></b><span style='font-family:Arial;mso-bidi-font-family: "Times New Roman"'> Dissolve 1.965 g of <i>cupric <span class=SpellE>sulphate</span>,<br /> </i>accurately weighed, in sufficient <i>0.1 M hydrochloric acid </i>to<i> </i>produce<br /> 1000.0 ml. Transfer 3.0 ml to a 1000 ml volumetric flask<i> </i>and dilute to<br /> volume with 0.1 <i>M <span class=SpellE>hdyrochloric</span> acid.</i></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Copper<br /> Standard Solution (10 <span class=SpellE>ppm</span> Cu):</span></b><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'> Dilute<br /> 1volume of a 0.393 per cent w/v solution of <i>cupric <span class=SpellE>sulphate</span> <br /> </i>to 100 volumes with <i>water.</i></span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=SpellE><b style='mso-bidi-font-weight:normal'><span style='font-family:Arial;mso-bidi-font-family: "Times New Roman"'>Digitoxin</span></b></span><b style='mso-bidi-font-weight: normal'><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'> <br /> Standard Solution; <span class=SpellE>Digitoxin</span> Reagent: </span></b><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Dissolve 0.125<br /> g of <span class=SpellE>digitoxin</span> RS in sufficient <i>glacial acetic<br /> acid </i>to produce 100.0 ml. Dilute 4.0 ml of this solution to 100.0 ml with <i>glacial<br /> acetic acid. </i>To 25.0 ml of the resulting solution add 3.0 ml of <i>water </i>and<br /> <span class=SpellE>mlx</span> well.</span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=SpellE><b style='mso-bidi-font-weight:normal'><span style='font-family:Arial;mso-bidi-font-family: "Times New Roman"'>Digoxin</span></b></span><b style='mso-bidi-font-weight: normal'><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'> <br /> Standard Solution:</span></b><span style='font-family:Arial;mso-bidi-font-family: "Times New Roman"'> Dissolve 0.125 g of <span class=SpellE><i>digoxin</i></span><i> <br /> RS </i>in sufficient <i>glacial acetic acid </i>to produce 100.0 ml. Dilute 4.0<br /> ml of this solution to 100.0 ml with <i>glacial acetic acid. </i>To 25.0 ml of<br /> the resulting solution add 3.0 ml of <i>water </i>and <span class=SpellE>mlx</span> <br /> well.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Formaldehyde<br /> Standard Solution (5 <span class=SpellE>ppm</span> CH<sub>2</sub>O):</span></b><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'> Dilute 1<br /> volume of a solution containing 3.0 g of <i>formaldehyde</i> <i>solution </i>in<br /> 1000.0 ml to 200 volumes with <i>water.</i></span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Iron<br /> Standard Solution (2 <span class=SpellE>ppm</span> Fe):</span></b><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'> Dilute<br /> 1volume of <i>iron standard solution (20 <span class=SpellE>ppm</span> Fe) </i>to<br /> 10 volumes with <i>water.</i></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Iron<br /> Standard Solution (8 <span class=SpellE>ppm</span> Fe):</span></b><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'> Dilute 4<br /> volumes of <i>iron standard solution (20 <span class=SpellE>ppm</span> Fe) </i>to<br /> 100 volumes with <span class=GramE><i>water .</i></span></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Iron<br /> Standard Solution (10 <span class=SpellE>ppm</span> Fe):</span></b><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'> Dissolve<br /> 7.022 g <span class=SpellE><i>offerrous</i></span><i> ammonium <span class=SpellE>sulphate</span> </i>in <i>water </i>containing 25 ml of 1<i>M <span class=SpellE>sulphuric</span> acid </i>and add sufficient <i>water </i>to<br /> produce 1000.0 ml. Dilute<i> </i>1 <span class=GramE>volume</span> to 100<br /> volumes with <i>water. </i>Contains iron in ferrous<i> </i>state.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Iron<br /> Standard Solution (20 <span class=SpellE>ppm</span> Fe):</span></b><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'> Dilute 1<br /> volume of a 0.1726 per cent w/v <i>solution of ferric ammonium <span class=SpellE>sulphate</span> </i>in <i>0.05 M <span class=SpellE>sulphuric</span> <br /> acid </i>to 10 volumes with <i>water. </i>Contains iron in ferric state.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Lead<br /> Standard Solution:</span></b><span style='font-family:Arial;mso-bidi-font-family: "Times New Roman"'> On the day of use, dilute 10 ml of <i>lead nitrate stock<br /> solution </i>with <i>water </i>to 100 ml. 1 ml of <i>lead</i> <i>standard<br /> solution </i>contains the equivalent of 10 !<span class=SpellE>lg</span> of<br /> lead. A control comparison solution prepared with 2.0 ml of <i>lead</i> <i>standard<br /> solution </i>contains, when compared to a solution representing 1.0 g of the<br /> substance under <span class=SpellE>examlnation</span>, the equivalent of 20 <span class=SpellE>ppm</span> of lead.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Lead<br /> Standard Solution (1 <span class=SpellE>ppm</span> <span class=SpellE>Pb</span>):</span></b><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'> Dilute<br /> 1volume of <i>lead standard solution (10 <span class=SpellE>ppm</span> <span class=SpellE>Pb</span>) </i>to 10 volumes with <i>water.</i></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Lead<br /> Standard Solution (2 <span class=SpellE>ppm</span> <span class=SpellE>Pb</span>):</span></b><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'> Dilute I<br /> volume of <i>lead standard solution (10 <span class=SpellE>ppm</span> <span class=SpellE>Pb</span>) </i>to 5 volumes with <i>water.</i></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Lead<br /> Standard Solution (10 <span class=SpellE>ppm</span> <span class=SpellE>Pb</span>):</span></b><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'> Dilute I<br /> volume of <i>lead standard solution (100 <span class=SpellE>ppm</span> <span class=SpellE>Pb</span>) </i>to 10 volumes with <i>water.</i></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Lead<br /> Standard Solution (20 <span class=SpellE>ppm</span> <span class=SpellE>Pb</span>):</span></b><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'> Dilute 1<br /> volume of <i>lead standard solution (100 <span class=SpellE>ppm</span> <span class=SpellE>Pb</span>) </i>to 5 volumes with <i>water.</i></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Lead<br /> Standard Solution (100 <span class=SpellE>ppm</span> <span class=SpellE>Pb</span>):</span></b><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'> Dilute 1<br /> volume of <i>lead standard solution (0.1 per cent <span class=SpellE>Pb</span>)<br /> </i>to 10 volumes with <i>water.</i></span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Lead<br /> Standard Solution (0.1 per cent <span class=SpellE>Pb</span>):</span></b><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'> Dissolve 0.4<br /> g of <i>lead nitrate </i>in <i>water </i>containing 2 ml of <i>nitric acid </i>and<br /> add sufficient <i>water </i>to produce 250.0 ml.</span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Nickel<br /> Standard Solution (10 <span class=SpellE>ppm</span> Ni):</span></b><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'> Dilute I<br /> volume of a 0.478 per cent w/v solution of <i>nickel <span class=SpellE>sulphate</span> <br /> </i>to 100 volumes with <i>water.</i></span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Nitrate<br /> Standard Solution (2 <span class=SpellE>ppm</span> N03):</span></b><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'> Dilute<br /> 1volume of <i>nitrate standard solution (100 <span class=SpellE>ppm</span> NOJ)<br /> </i>to 50 volumes with <i>water.</i></span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Nitrate<br /> Standard Solution (100 <span class=SpellE>ppm</span> N03):</span></b><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'> Dilute<br /> 1volume of a 0.163 per cent w/v solution of <i>potassium nitrate </i>to 10<br /> volumes with <i>water.</i></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Phosphate<br /> Standard Solution (5 <span class=SpellE>ppm</span> P04):</span></b><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'> Dilute<br /> 1volume of a 0.143 per cent w/v solution of <i>potassium <span class=SpellE>dihydrogen</span></i> <br /> <i>phosphate </i>to 200 volumes with <i>water.</i></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Silver<br /> Standard Solution (5 <span class=SpellE>ppm</span> Ag):</span></b><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'> Dilute<br /> 1volume of a 0.079 per cent w/v solution of <i>silver nitrate </i>to 100<br /> volumes with <i>water.</i></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span class=SpellE><b style='mso-bidi-font-weight:normal'><span style='font-family:Arial;mso-bidi-font-family: "Times New Roman"'>Sulphate</span></b></span><b style='mso-bidi-font-weight: normal'><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'> <br /> Standard Solution (10 <span class=SpellE>ppm</span> S04):</span></b><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'> Dilute I<br /> volume of a 0.181 per cent w/v solution of <i>potassium <span class=SpellE>sulphate</span> <br /> </i>in <i>distilled</i> <i>water </i>to 100 volumes with the same solvent.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'>.<span class=SpellE>Sulphate</span> Standard Solution (10 <span class=SpellE>ppm</span> <br /> S04), <span class=SpellE>Ethanolic</span>:</span></b><span style='font-family: Arial;mso-bidi-font-family:"Times New Roman"'> Dilute 1 volume of a 0.181 per<br /> cent w/v solution of <i>potassium <span class=SpellE>sulphate</span></i> in <i>ethanol<br /> (30 per cent) </i>to 100 volumes with <i>ethanol (30 per</i> <i>cent).</i></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Tin<br /> Standard Solution (5 <span class=SpellE>ppm</span> <span class=SpellE>Sn</span>):</span></b><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'> Dissolve 0.5<br /> g of <i>tin </i>in <span class=GramE>a</span> <span class=SpellE>mlxture</span> <br /> of 5 ml of <i>water </i>and 25 ml of <i>hydrochloric acid </i>and add<br /> sufficient <i>water </i>to produce 1000.0 ml. Dilute 1 volume of this solution<br /> to 100 volumes with a 2.5 per cent v/v solution of <i>hydrochloric acid.</i></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Zinc<br /> Standard Solution (10 <span class=SpellE>ppm</span> Zn):</span></b><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'> Dilute<br /> 1volume of <i>zinc standard solution (100 <span class=SpellE>ppm</span> Zn) </i>to<br /> 10 volumes with <i>water.</i></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Zinc<br /> Standard Solution (25 <span class=SpellE>ppm</span> Zn):</span></b><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'> Dilute 25<br /> volumes of <i>zinc standard solution </i>(100 <span class=SpellE><i>ppm</i></span><i> <br /> Zn) </i>to 100 volumes with <i>water.</i></span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><b style='mso-bidi-font-weight: normal'><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'>Zinc<br /> Standard Solution (100 <span class=SpellE>ppm</span> Zn):</span></b><span style='font-family:Arial;mso-bidi-font-family:"Times New Roman"'> Dissolve<br /> 0.440 g of <i>zinc <span class=SpellE>sulphate</span> </i>in <i>water </i>containing<br /> 1 ml of 5M acetic acid and add sufficient <i>water </i>to produce 100.0 ml.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='mso-layout-grid-align:none'><span style='font-family: Arial;mso-bidi-font-family:"Times New Roman"'>Dilute 1 volume of this solution<br /> to 10 volumes with <i>water </i>immediately before use.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><o:p> </o:p></p> <br /> </div> <br /> </body> <br /> <br /> </html>http://scholarpharma.blogspot.com/2012/01/preparation-of-standard-solutions.html1margipatel02@gmail.com (margipatel02@gmail.com)tag:blogger.com,1999:blog-8563020669307343167.post-5736524642948673122Fri, 06 Jan 2012 03:31:00 +00002012-01-05T19:36:08.865-08:00Preparation of Buffer SolutionsPreparation of Buffer Solutions<html xmlns:v="urn:schemas-microsoft-com:vml" xmlns:o="urn:schemas-microsoft-com:office:office" xmlns:w="urn:schemas-microsoft-com:office:word" xmlns="http://www.w3.org/TR/REC-html40"> <br /> <br /> <head> <br /> <meta http-equiv=Content-Type content="text/html; charset=windows-1252"> <br /> <meta name=ProgId content=Word.Document> <br /> <meta name=Generator content="Microsoft Word 11"> <br /> <meta name=Originator content="Microsoft Word 11"> <br /> <link rel=File-List href="Preparation%20of%20Buffer%20Solutions_files/filelist.xml"> <br /> <link rel=Edit-Time-Data href="Preparation%20of%20Buffer%20Solutions_files/editdata.mso"> <br />  <br /> <title>Preparation of Buffer Solutions - RAJARSSHI PATEL</title> <br />  <br /> <style>  </style> <br />  <br /> </head> <br /> <br /> <body lang=EN-US link=blue vlink=blue style='tab-interval:.5in'> <br /> <br /> <div class=Section1> <br /> <p class=MsoNormal style='mso-margin-top-alt:auto;mso-margin-bottom-alt:auto; mso-outline-level:3'><b><span style='font-size:13.5pt;mso-bidi-font-family: "Times New Roman"'>Preparation of Buffer Solutions<span style='mso-spacerun:yes'> </span>- RAJARSHI PATEL<o:p></o:p></span></b></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Standard<br /> Buffer Solutions</span></b><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Standard<br /> Buffer Solutions are solutions of standard pH. They are used for reference<br /> purposes in pH measurements and for carrying out many <span class=SpellE>pharmacopoeial</span> <br /> tests which require adjustments to or maintenance of a specified pH. They may<br /> be prepared by the methods described below. The preparation of special buffer<br /> solutions is described in the sections in which their use is specified as in<br /> the <i>microbiological assay of</i> <i>antibiotics </i>or in the individual<br /> monographs where the use of such solutions is indicated.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>The<br /> reagents required for the preparation of standard buffer solutions are<br /> described in Appendix 4.2. All the crystalline reagents except boric acid<br /> should be dried at 110° to 120° for 1 hour before use. <i>Carbon dioxide-free<br /> water </i>should be used for preparing buffer solutions and wherever <i>water </i>is<br /> mentioned for preparation of such solutions the use of <i>carbon</i> <i>dioxide-free<br /> water </i>is implied. The prepared solutions should be stored in chemically<br /> resistant, glass-<span class=SpellE>stoppered</span> bottles of <span class=SpellE>alkakli</span>-free glass and used within 3 months of preparation.<br /> Any solution which has become cloudy or shows any other evidence of<br /> deterioration should be discarded.</span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Standard<br /> buffer solutions for various ranges of pH values 1.2 to 10.0 may be prepared by<br /> appropriate combinations of <i>0.2 M hydrochloric acid </i>or <i>0.2 M sodium<br /> hydroxide </i>and of solutions described below, used in the proportions shown<br /> in the accompanying tables. The standard pH values given in the tables and<br /> elsewhere in the Appendix are considered to be reproducible within </span><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>±<br /> </span><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>0.02<br /> Unit at 25°.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>1.<br /> Boric Acid and Potassium Chloride, 0.2 M:</span></b><span style='font-size: 9.0pt;mso-bidi-font-family:"Times New Roman"'> Dissolve 12.366 g of <i>boric<br /> acid </i>and 14.911 g of <i>potassium chloride </i>in</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><i><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>water<br /> </span></i><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>and<br /> dilute with <i>water </i>to 1000 ml.</span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>2.<br /> <span class=SpellE>Disodium</span> Hydrogen Phosphate, 0.2 M:</span></b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'> Dissolve 71.630<br /> g of <span class=SpellE><i>disodium</i></span><i> hydrogen phosphate </i>in <i>water<br /> </i>and dilute with <i>water </i>to 1000 ml.</span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>3.<br /> Hydrochloric Acid, 0.2 M:</span></b><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman"'> <i>Hydrochloric acid </i>diluted with <i>water </i>to<br /> contain 7.292 g of <span class=SpellE>HCl</span> in 1000 ml.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>4.<br /> Potassium Chloride, 0.2 M:</span></b><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman"'> Dissolve 14.911 g of <i>potassium chloride </i>in <i>water </i>and<br /> dilute with <i>water </i>to 1000 ml.</span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>5.<br /> Potassium <span class=SpellE>Dihydrogen</span> Phosphate, 0.2 M:</span></b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'> Dissolve 27.218<br /> g of <i>potassium <span class=SpellE>dihydrogen</span> phosphate </i>in <i>water<br /> </i>and dilute with <i>water </i>to 1000 ml.</span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>6.<br /> Potassium Hydrogen Phthalate, 0.2 M:</span></b><span style='font-size:9.0pt; mso-bidi-font-family:"Times New Roman"'> Dissolve 40.846 g of <i>potassium<br /> hydrogen phthalate </i>in <i>water </i>and dilute with <i>water </i>to 1000 ml.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>7.<br /> Sodium Hydroxide, 0.2 M:</span></b><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman"'> Dissolve <i>sodium hydroxide </i>in <i>water </i>to produce<br /> a 40 to 60 per cent w/v solution and allow to stand. Taking precautions to<br /> avoid absorption of carbon dioxide, siphon off the clear supernatant liquid and<br /> dilute with <i>carbon dioxide-free water, </i>a suitable volume of the liquid<br /> to contain 8.0 g of <span class=SpellE>NaOH</span> in 1000 ml. </span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><i><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman"'>NOTE </span></i></b><b><span style='font-size:9.0pt; mso-bidi-font-family:"Times New Roman"'>-</span></b><span style='font-size: 9.0pt;mso-bidi-font-family:"Times New Roman"'> <i>0.2 M Sodium hydroxide must<br /> not be used later than one month after preparation.</i></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><span style='mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Composition<br /> of Standard Buffer Solutions</span></b><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Hydrochloric<br /> Acid Buffer: Place 50.0 <span class=SpellE>mI</span> of the <i>0.2Mpotassium<br /> chloride </i>in a 200 ml volumetric flask, add the specified volume<i> </i>of <i>0.2<br /> M hydrochloric acid </i>(see Table I) and then add <i>water </i>to volume.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal align=center style='text-align:center'><span style='mso-bidi-font-family:"Times New Roman"'><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhXoF3uzn7ahR8SYCvIvzgVy1YL_CU8efmORSwPrlyx0YHI_DCRDOgccKzi-IdHW2w-30oz55-PcRLPFYeQSiqWNBIXrvl5lMgi2JKDdhK0u3Jd2RFgpk_axy1R6Dj7dh_loBOthGYOJyo/s1600/Buffer.bmp"><span style='text-decoration:none;text-underline:none'><![if !vml]><span style='mso-ignore:vglayout'><img border=0 width=301 height=155 src="Preparation%20of%20Buffer%20Solutions_files/image001.jpg" v:shapes="_x0000_i1025"></span><![endif]></span></a><br> <br /> <br style='mso-special-character:line-break'> <br /> <![if !supportLineBreakNewLine]><br style='mso-special-character:line-break'> <br /> <![endif]><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Acid<br /> Phthalate Buffer:</span></b><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman"'> Place 50.0 ml of <i>0.2 M potassium hydrogen phthalate </i>in<br /> a 200 ml volumetric flask, add the<i> </i>specified volume of <i>0.2 M<br /> hydrochloric acid </i>(see Table 2)<i> </i>and then add <i>water </i>to volume.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal align=center style='text-align:center'><span style='mso-bidi-font-family:"Times New Roman"'><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgzjWvt7iNI3fwoEKX8E6bRH-HD1aEca-7ti70Rv4RGhk0JLBp3WUs00TtO6Ue7htEj_4g-PiYt3nVxFH3XvozJuMXEtH5BEGGgesl4gBjoXrkIUKE7BOy1BCAEcagwMz-UPt7FLBh7PH0/s1600/Buffer.bmp"><span style='text-decoration:none;text-underline:none'><![if !vml]><span style='mso-ignore:vglayout'><img border=0 width=301 height=140 src="Preparation%20of%20Buffer%20Solutions_files/image002.jpg" v:shapes="_x0000_i1026"></span><![endif]></span></a><br style='mso-special-character:line-break'> <br /> <![if !supportLineBreakNewLine]><br style='mso-special-character:line-break'> <br /> <![endif]><o:p></o:p></span></p> <br /> <p class=MsoNormal><span class=SpellE><b><span style='font-size:9.0pt; mso-bidi-font-family:"Times New Roman"'>Neutralised</span></b></span><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'> Phthalate<br /> Buffer; Phthalate Buffer:</span></b><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman"'> Place 50.0 ml of <i>0.2 M potassium hydrogen phthalate </i>in<br /> a 200 ml volumetric flask, add the specified volume of <i>0.2 M sodium</i> <i>hydroxide<br /> </i>(see Table 3) and then add <i>water </i>to volume.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal align=center style='text-align:center'><span style='mso-bidi-font-family:"Times New Roman"'><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEgj65q5FKGI85ayqHYHMmKbpb-ijDgbtVwknjqV4J_p5WQ0w5pWff7vZCjNcpBBMJi_1oCfxsgQzD3FkArLghG9iYwNMjv2Ktlu7j0Vqyu8LoVh6VuJlpZsqUSL70yGIUr7II4MelE2Il4/s1600/Buffer+1.bmp"><span style='text-decoration:none;text-underline:none'><![if !vml]><span style='mso-ignore:vglayout'><img border=0 width=301 height=131 src="Preparation%20of%20Buffer%20Solutions_files/image003.jpg" v:shapes="_x0000_i1027"></span><![endif]></span></a><br> <br /> <br style='mso-special-character:line-break'> <br /> <![if !supportLineBreakNewLine]><br style='mso-special-character:line-break'> <br /> <![endif]><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Phosphate<br /> Buffer:</span></b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'> <br /> Place 50.0 ml of <i>0.2 M potassium <span class=SpellE>dihydrogen</span> <br /> phosphate </i>in a 200 ml volumetric flask, add the<i> </i>specified volume of <i>0.2<br /> M sodium hydroxide </i>(see Table 4)<i> </i>and then add <i>water </i>to<br /> volume.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal align=center style='text-align:center'><span style='mso-bidi-font-family:"Times New Roman"'><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEj1BLClCaEkxWE5BVm2TuuZ2VR65HEanaIkePFvUl_XyDsHK2P0OCJjKYqtoTF94pa1OiNfSC5giu2B7fXbtCIeTStv9iU3F6gxCd5K9rQyQsmzIUjNWYRkNujjWcRSf5omIyjrLdpFm0A/s1600/Buffer+1.bmp"><span style='text-decoration:none;text-underline:none'><![if !vml]><span style='mso-ignore:vglayout'><img border=0 width=301 height=150 src="Preparation%20of%20Buffer%20Solutions_files/image004.jpg" v:shapes="_x0000_i1028"></span><![endif]></span></a><o:p></o:p></span></p> <br /> <p class=MsoNormal style='margin-bottom:12.0pt'><b><span style='font-size:9.0pt; mso-bidi-font-family:"Times New Roman"'>Alkaline Borate Buffer:</span></b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'> Place 50.0 ml<br /> of <i>0.2 M boric acid </i>and <i>potassium chloride </i>in a 200 ml volumetric<br /> flask, add the<i> </i>specified volume of <i>0.2 M sodium hydroxide </i>(see<br /> Table 5)<i> </i>and then add <i>water </i>to volume.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal align=center style='text-align:center'><span style='mso-bidi-font-family:"Times New Roman"'><a href="https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEi_H8nOUIrgJYIDNuJNA2Rie5_f1XXIuXnQhUNeLIOPHDljj0Rtr4pgggoI8MEkrs7dRGw1c1ZWZ86okBvqoC1yifZtxba8cdrIpCaD-EuRwN53aoYoWxZmrdh0V1CLYQUM51tyjWx53a8/s1600/Buffer+1.bmp"><span style='text-decoration:none;text-underline:none'><![if !vml]><span style='mso-ignore:vglayout'><img border=0 width=301 height=159 src="Preparation%20of%20Buffer%20Solutions_files/image005.jpg" v:shapes="_x0000_i1029"></span><![endif]></span></a><br style='mso-special-character:line-break'> <br /> <![if !supportLineBreakNewLine]><br style='mso-special-character:line-break'> <br /> <![endif]><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:10.0pt;mso-bidi-font-family:"Times New Roman"'>Other<br /> Buffer solutions</span></b><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Acetate<br /> Buffer pH 2.8:</span></b><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman"'> Dissolve 4 g of <i>anhydrous sodium acetate </i>in about<br /> 840 ml of <i>water, </i>add sufficient <i>glacial acetic acid </i>to adjust the<br /> pH to 2.8 (about 155 ml) and dilute with<i> water </i>to 1000 ml.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Acetate<br /> Buffer pH 3.4:</span></b><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman"'> Mix 50 ml of <i>0.1 M sodium acetate </i>with 950 ml of <i>0.1<br /> M acetic acid.</i></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Acetate<br /> Buffer pH 3.5:</span></b><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman"'> Dissolve 25 g of <i>ammonium acetate </i>in 25 ml of <i>water<br /> </i>and add 38 ml of 7 <i>M hydrochloric acid.</i> Adjust the pH to 3.5 with<br /> either 2 <i>M hydrochloric acid </i>or <i>6 M ammonia </i>and dilute with <i>water<br /> </i>to 100 ml.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Acetate<br /> Buffer pH 3.7:</span></b><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman"'> Dissolve 10 g of <i>anhydrous sodium acetate </i>in 300 ml<br /> of <i>water, </i>adjust the pH to 3.7 with <i>glacial acetic acid </i>and<br /> dilute with <i>water </i>to 1000 ml. Before use adjust<i> </i>to pH 3.7, if<br /> necessary, with <i>glacial acetic acid </i>or <i>anhydrous sodium acetate, </i>as<br /> required.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Acetate<br /> Buffer pH 4.0:</span></b><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman"'> Place 2.86 ml of <i>glacial acetic acid </i>and 1.0 ml of a<br /> 50 per cent w/v solution of <i>sodium hydroxide </i>in a 1000 ml volumetric<br /> flask, add <i>water </i>to volume and mix.<i> </i>Adjust the pH, if necessary.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Acetate<br /> Buffer pH 4.4:</span></b><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman"'> Dissolve 136 g of <i>sodium acetate </i>and 77 g of <i>ammonium<br /> acetate </i>in <i>water </i>and dilute with <i>water </i>to 1000 ml. Add 250 ml<br /> of <i>glacial acetic acid </i>and mix.</span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Acetate<br /> Buffer pH 4.6:</span></b><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman"'> Dissolve 5.4 g of <i>sodium acetate </i>in 50 ml of <i>water,<br /> </i>add 2.4 ml of <i>glacial acetic acid </i>and dilute with <i>water </i>to<br /> 100 ml. Adjust the pH, if necessary.</span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Acetate<br /> Buffer pH 4.7:</span></b><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman"'> Dissolve 8.4 g of <i>sodium acetate </i>and 3.35 ml of <i>glacial<br /> acetic acid </i>in sufficient <i>water </i>to produce 1000 ml. Adjust the pH,<br /> if necessary.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Acetate<br /> Buffer pH 5.0:</span></b><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman"'> Dissolve 13.6 g of <i>sodium acetate </i>and6 ml of <i>glacial<br /> acetic acid </i>in sufficient <i>water </i>to produce 1000 ml. Adjust the pH,<br /> if necessary.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Acetate<br /> Buffer pH 5.5:</span></b><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman"'> Dissolve 272 g of <i>sodium acetate </i>in 500 ml of <i>water<br /> </i>by heating to 35°, cool and add slowly 50 ml of <i>glacial acetic acid </i>and<br /> sufficient <i>water </i>to produce 1000 ml. Adjust the pH, if necessary.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Acetate<br /> Buffer pH 6.0:</span></b><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman"'> <span class=SpellE>Dissol</span> <span class=SpellE>ve</span> <br /> 100 g of <i>ammonium acetate </i>in 300 ml of <i>water, </i>add 4.1 ml of <i>glacial<br /> acetic acid, </i>adjust the<i> </i>pH, if necessary, using <i>10M ammonia </i>or<br /> 5 <i>M acetic acid </i>and<i> </i>dilute with <i>water </i>to 500 ml.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Acetate<br /> Buffer Solution:</span></b><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman"'> Dissolve 14 g of <i>potassium acetate </i>and 20.5 ml of <i>glacial<br /> acetic acid </i>in sufficient <i>water </i>to produce 1000 ml.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Acetate-<span class=SpellE>Edetate</span> Buffer pH 5.5:</span></b><span style='font-size: 9.0pt;mso-bidi-font-family:"Times New Roman"'> Dissolve 250 g of <i>ammonium<br /> acetate </i>and 15 g of <span class=SpellE><i>disodium</i></span><i> <span class=SpellE>edetate</span> </i>in 400 ml of <i>water </i>and<i> </i>add 125 ml<br /> of <i>glacial acetic acid </i>in sufficient water to produce<i> </i>1000ml.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Acetic<br /> Acid-Ammonium Acetate Buffer:</span></b><span style='font-size:9.0pt; mso-bidi-font-family:"Times New Roman"'> Dissolve 77.1 g of <i>ammonium acetate<br /> </i>in <i>water, </i>add 57 ml of <i>glacial acetic acid</i> and dilute with <i>water<br /> </i>to 1000 ml.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Acetic<br /> Ammonia Buffer pH 3.7, <span class=SpellE>Ethanolic</span>:</span></b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'> To 15 ml of <i>5<br /> M acetic acid </i>add 60 ml of <i>ethanol </i>(95 <i>per cent) </i>and 24 ml of<br /> <i>water. </i>Adjust the pH to 3.7 with <i>10 M ammonia </i>and dilute with <i>water<br /> </i>to 100 ml.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Acetone<br /> Solution, Buffered:</span></b><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman"'> Dissolve 8. 15 g of <i>sodium acetate </i>and 42 g of <i>sodium<br /> chloride </i>in <i>water, </i>add 68 ml of<i> 0.1 M hydrochloric acid </i>and<br /> 150 ml of <i>acetone </i>and dilute with <i>water </i>to 500 ml.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Albumin<br /> Phosphate Buffer pH 7.2; </span></b><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman"'>Phosphate-albumin</span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Buffered<br /> Saline pH 7.2:</span></b><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman"'> Dissolve 10.75 g of <span class=SpellE><i>disodium</i></span><i> <br /> hydrogen phosphate, </i>7.6 g of <i>sodium chloride </i>and 10 g of<i> bovine<br /> albumin </i>in sufficient <i>water </i>to produce 1000 ml. Before<i> </i>use<br /> adjust to pH 7.2 with 2 M <i>sodium hydroxide </i>or a 10 per<i> </i>cent w/v<br /> solution of <i>phosphoric acid </i>as required.</span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Ammonia-Ammonium<br /> Chloride Buffer:</span></b><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman"'> Dissolve 67.5 g of <i>ammonium chloride </i>in about 200 ml<br /> of <i>water, </i>add 570 ml of <i>strong ammonia solution </i>and dilute with <i>water<br /> </i>to 1000 ml.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Ammonia<br /> Buffer pH 9.5:</span></b><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman"'> Dissolve 33.5 g of <i>ammonium chloride </i>in ISO ml of <i>water,<br /> </i>and 42 ml of <i>10M ammonia </i>and dilute with <i>water </i>to 250 ml.<br /> Store in polyethylene containers.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Ammonia<br /> Buffer pH 10.0:</span></b><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman"'> Dissolve 5.4 g of <i>ammonium chloride </i>in 20 ml of <i>water,<br /> </i>add 35 ml of 10 <i>M ammonia </i>and dilute with <i>water </i>to 100 ml.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Ammonia<br /> Buffer pH 10.9:</span></b><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman"'> Dissolve 67.5 g of <i>ammonium chloride </i>in sufficient <i>10<br /> M ammonia </i>to produce 1000 ml.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><span class=SpellE><b><span style='font-size:9.0pt; mso-bidi-font-family:"Times New Roman"'>Barbitone</span></b></span><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'> Buffer pH 7.4: </span></b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Mix 50 ml of<br /> solution containing 1.944 per cent w/v of <i>sodium acetate </i>and 2.946 per<br /> cent w/v of <span class=SpellE><i>barbitone</i></span><i> sodium </i>with 50.5<br /> ml of <i>0.1 M hydrochloric acid,</i> add 20 ml of an 8.5 per cent w/v solution<br /> of <i>sodium chloride</i> and dilute with <i>water </i>to 250 ml.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><span class=SpellE><b><span style='font-size:9.0pt; mso-bidi-font-family:"Times New Roman"'>Barbitone</span></b></span><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'> Buffer pH 8.6,<br /> Mixed;</span></b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'> <br /> <span class=SpellE><b>Barbitone</b></span><b> Buffer pH 8.6:</b> Dissolve 1.38<br /> g of <span class=SpellE><i>barbitone</i></span><i>, </i>8.76 g of <span class=SpellE><i>barbitone</i></span><i> sodium </i>and 0.38 g of <i>calcium<br /> lactate </i>in sufficient <i>water </i>to produce 1000 ml.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Boric<br /> Buffer pH 9.0; Borate Buffer pH 9.0:</span></b><span style='font-size:9.0pt; mso-bidi-font-family:"Times New Roman"'> Dissolve 6.20 g of <i>boric acid </i>in<br /> 500 ml of <i>water, </i><span class=SpellE>adjustto</span> pH 9.0 with] <i>M<br /> sodium</i> <i>hydroxide </i>(about 41.5 ml) and dilute with <i>water </i>to<br /> 1000 ml.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Buffer<br /> Solution pH 2.5:</span></b><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman"'> To 25.0 ml of <i>0.2 M potassium hydrogen phthalate </i>add<br /> 37.0 ml of <i>0.1 M hydrochloric acid </i>and dilute with sufficient <i>water </i>to<br /> produce 100.0 ml.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Buffer<br /> (HEPES) solution pH 7.5:</span></b><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman"'> Dissolve 2.38 g of <i>2[4-( <span class=SpellE>hydroxyethyl</span>)piperazin-1-yljethanesulphonic<br /> acid </i>in about 90 ml of <i>water. </i>Adjust the pH to 7.5 with <i>sodium</i> <br /> <i>hydroxide solution. </i>Dilute to 100 ml with <i>water.</i></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Carbonate<br /> Buffer pH 9.7:</span></b><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman"'> Dissolve 8.4 g of <i>sodium bicarbonate </i>and 10.6 g of <i>sodium<br /> carbonate </i>in sufficient<i> water </i>to produce 500 ml.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Chloride<br /> Buffer pH 2.0:</span></b><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman"'> Dissolve 6.57 g of <i>potassium chloride </i>in <i>water, </i>add<br /> 119.0 ml of <i>0.1 M hydrochloric acid </i>and dilute<i> </i>with <i>water </i>to<br /> 1000 ml.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Citrate<br /> Buffer:</span></b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'> <br /> Dissolve 0.5 g of <i>citric acid monohydrate </i>and 0.4 g of <i>dibasic sodium<br /> phosphate </i>in sufficient <i>water </i>to<i> </i>produce 1000 ml.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><span class=SpellE><b><span style='font-size:9.0pt; mso-bidi-font-family:"Times New Roman"'>Citro</span></b></span><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>-phosphate<br /> Buffer pH 5.0:</span></b><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman"'> Mix 48.5 ml of <i>0.1 M citric acid </i>with sufficient <i>0.2<br /> M <span class=SpellE>disodium</span> hydrogen phosphate </i>to<i> </i>produce<br /> 100 ml.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><span class=SpellE><b><span style='font-size:9.0pt; mso-bidi-font-family:"Times New Roman"'>Citro</span></b></span><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>-phosphate<br /> Buffer pH 6.0:</span></b><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman"'> Mix 36.8 ml of a 2.1 per cent w/v solution of <i>citric<br /> acid </i>with 63.2 ml of a 7.15 per cent w/v solution of <span class=SpellE><i>disodium</i></span><i> <br /> hydrogen phosphate.</i></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><span class=SpellE><b><span style='font-size:9.0pt; mso-bidi-font-family:"Times New Roman"'>Citro</span></b></span><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>-phosphate<br /> Buffer pH 7.0:</span></b><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman"'> Mix 17.6 ml of a 2.1 percent w/v solution of <i>citric acid<br /> </i>with 82.4 ml of a 7.15 per cent w/v solution of <span class=SpellE><i>disodium</i></span><i> <br /> hydrogen phosphate.</i></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><span class=SpellE><b><span style='font-size:9.0pt; mso-bidi-font-family:"Times New Roman"'>Citro</span></b></span><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>-phosphate<br /> Buffer pH 7.2:</span></b><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman"'> Mix 13.0 ml of a 2.1 percent w/v solution of <i>citric acid<br /> </i>with 87.0 ml of a 7.15 per cent w/v solution of <span class=SpellE><i>disodium</i></span><i> <br /> hydrogen phosphate.</i></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><span class=SpellE><b><span style='font-size:9.0pt; mso-bidi-font-family:"Times New Roman"'>Citro</span></b></span><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>-phosphate<br /> Buffer pH 7.6:</span></b><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman"'> Dissolve 1.33 g of <i>citric acid </i>and 67.1 g of <span class=SpellE><i>disodium</i></span><i> hydrogen phosphate </i>in sufficient <i>water<br /> </i>to produce 1000 ml.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Cupric<br /> <span class=SpellE>Sulphate</span> Solution pH 2.0, Buffered:</span></b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'> Mix 5.3 ml of <i>0.2<br /> M hydrochloric acid </i>and 25 ml of <i>0.2 M potassium</i> <i>chloride, </i>add<br /> 4 ml of a 0.393 per cent w/v solution of <i>cupric</i> <span class=SpellE><i>sulphate</i></span><i> <br /> </i>and dilute to 100 ml of <i>water.</i></span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Cupric<br /> <span class=SpellE>Sulphate</span> Solution pH 4.0, Buffered:</span></b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'> Dissolve 0.25 g<br /> <i>cupric <span class=SpellE>sulphate</span> </i>and 4.5 g of <i>ammonium<br /> acetate </i>in sufficient <i>water </i>to produce 100 ml.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Cupric<br /> <span class=SpellE>Sulphate</span> Solution pH 5.2, Buffered:</span></b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'> Dissolve 1.522<br /> g of <i>anhydrous <span class=SpellE>disodium</span> hydrogen phosphate </i>in<br /> sufficient <i>water </i>to produce 53.6 ml and add a 2.1 per cent solution of <i>citric<br /> acid </i>until the pH of the solution is between 5.15 and 5.25 (about 46 ml).<br /> Mix 98.5 ml of the resulting solution with 1.5 ml of a 0.393 per cent solution<br /> of <i>cupric <span class=SpellE>sulphate</span>.</i></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><span class=SpellE><b><span style='font-size:9.0pt; mso-bidi-font-family:"Times New Roman"'>Diethanolamine</span></b></span><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'> Buffer pH 10.0:</span></b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'> Dissolve 96.4 g<br /> of <span class=SpellE><i>diethanolamine</i></span><i> </i>in sufficient <i>water<br /> </i>to produce 400 ml. Add 0.5 ml of an 18.6 per cent w/v solution of <i>magnesium<br /> chloride,</i> adjust the pH to 10.0 with 1 <i>M hydrochloric acid </i>and<br /> dilute with <i>water </i>to 500 ml.</span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><span class=SpellE><b><span style='font-size:9.0pt; mso-bidi-font-family:"Times New Roman"'>Glycine</span></b></span><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'> Buffer pH 11.3:</span></b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'> Mix a solution<br /> containing 0.75 per cent w/v of <span class=SpellE><i>glycine</i></span><i> </i>and<br /> 0.58 per cent w/v of <i>sodium chloride</i> with an equal volume of <i>0.1 M<br /> sodium hydroxide. </i>Adjust the pH if necessary.</span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><span class=SpellE><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman"'>Glycine</span></span><span style='font-size:9.0pt; mso-bidi-font-family:"Times New Roman"'> Buffer Solution: Mix 42 g of <i>sodium<br /> bicarbonate </i>and 50 g of <i>potassium bicarbonate </i>with 180 ml of <i>water<br /> </i>and<i> </i>add a solution containing 37.5 g of <span class=SpellE><i>glycine</i></span><i> <br /> </i>and IS ml of <i>strong ammonia </i>in 180 ml of <i>water. </i>Dilute with <i>water<br /> </i>to 500 ml and<i> </i>stir until solution is complete.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><span class=SpellE><b><span style='font-size:9.0pt; mso-bidi-font-family:"Times New Roman"'>Imidazole</span></b></span><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'> Buffer pH 6.5:</span></b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'> Dissolve 6.81 g<br /> of <span class=SpellE><i>imidazole</i></span><i> </i>and 1.23 g of <i>magnesium<br /> <span class=SpellE>sulphate</span> </i>in 752 ml of <i>0.] M hydrochloric</i> <i>acid,<br /> </i>adjust the pH if necessary and dilute with <i>water </i>to produce 1000 ml.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><span class=SpellE><b><span style='font-size:9.0pt; mso-bidi-font-family:"Times New Roman"'>Imidazole</span></b></span><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'> Buffer pH 7.4:</span></b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'> Dissolve 3.40 g<br /> of <span class=SpellE><i>imidazole</i></span><i> </i>and 5.84 g of <i>sodium<br /> chloride </i>in <i>water, </i>and 18.6 ml of] <i>M hydrochloric</i> <i>acid </i>and<br /> dilute with <i>water </i>to produce 1000 ml.</span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Palladium<br /> Chloride Solution, Buffered:</span></b><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman"'> To 0.5 g of <i>palladium chloride </i>add 5 ml of <i>hydrochloric<br /> acid </i>and warm on a <span class=SpellE>waterbath</span>.<i> </i>Add 200 <i>ml<br /> </i>of hot <i>water </i>in small portions with continued<i> </i>heating until<br /> solution is complete. Cool and dilute with<i> </i>sufficient <i>water </i>to<br /> produce 250.0 ml. To 50.0 ml of the resulting<i> </i>solution add 10.0 ml of] <i>M<br /> sodium acetate, </i>9.6 <i>ml of] M hydrochloric acid </i>and sufficient <i>water<br /> </i>to produce 100.0 ml.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Phosphate-albumin<br /> buffered saline pH 7.2:</span></b><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman"'> Dissolve 10.75 g of <span class=SpellE><i>disodium</i></span><i> <br /> hydrogen phosphate, </i>7.6 g of <i>sodium chloride</i> and 10 g of <i>bovine<br /> albumin </i>in <i>water </i>and dilute to 1000.0 ml with the same solvent.<br /> Immediately before use adjust the pH using <i>dilute sodium hydrogen solution </i>or<br /> <i>dilute</i> <i>phosphoric acid.</i></span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Phosphate<br /> Buffer pH 2.0:</span></b><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman"'> Dissolve 0.136 g of <i>potassium <span class=SpellE>dihydrogen</span> <br /> phosphate </i>in 800 ml of <i>water, </i>adjust the pH to 2.0<i> </i>with <i>hydrochloric<br /> acid </i>and add sufficient <i>water </i>to produce l000ml.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Phosphate<br /> Buffer pH 2.5</span></b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>:<br /> Dissolve 100 g of <i>potassium <span class=SpellE>dihydrogen</span> phosphate </i>in<br /> 800 ml of <i>water, </i>adjust the pH to 2.5<i> </i>with <i>hydrochloric acid </i>and<br /> add sufficient <i>water </i>to produce<i> </i>l000ml.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Phosphate<br /> Buffer pH 3.0:</span></b><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman"'> Dissolve 1.36 g of <i>potassium <span class=SpellE>dihydrogen</span> <br /> orthophosphate </i>and 2 ml of <span class=SpellE><i>triethylamine</i></span><i> <br /> </i>in 800<i> </i>ml of <i>water, </i>adjust the pH to 3.0 with <span class=SpellE><i>orthophosphoric</i></span><i> acid </i>and add sufficient <i>water<br /> </i>to produce 1000 ml.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Phosphate<br /> Buffer pH 3.6:</span></b><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman"'> Dissolve 0.900 g of <i>anhydrous <span class=SpellE>disodium</span> <br /> hydrogen phosphate </i>and 1.298 g of <i>citric acid monohydrate </i>in<br /> sufficient <i>water </i>to produce 1000 ml.</span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Phosphate<br /> Buffer pH 4.0, Mixed:</span></b><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman"'> Dissolve 5.04 g <span class=SpellE><i>disodium</i></span><i> <br /> hydrogen phosphate </i>and 3.01 g of <i>potassium <span class=SpellE>dihydrogen</span> <br /> phosphate </i>in sufficient <i>water </i>to produce 1000 ml. Adjust the<i> </i>pH<br /> with <i>glacial acetic acid.</i></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Phosphate<br /> Buffer pH 4.9:</span></b><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman"'> Dissolve 40 g of <i>sodium <span class=SpellE>dihydrogen</span> <br /> phosphate </i>and 1.2 g of <i>sodium hydroxide </i>in sufficient <i>water </i>to<br /> produce 100 ml. If necessary, adjust the pH with 1 M <span class=SpellE><i>sulphuric</i></span><i> <br /> acid </i>or <i>1 M sodium hydroxide </i>as required.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Phosphate<br /> Buffer pH 5.0:</span></b><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman"'> Dissolve 6.8 g of <i>potassium <span class=SpellE>dihydrogen</span> <br /> phosphate </i>in 1000 ml of <i>water </i>and adjust the pH<i> </i>to 5.0 with<br /> ]0 <i>M potassium hydroxide.</i></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Phosphate<br /> Buffer pH 5.5, Mixed:</span></b><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:7.0pt;mso-bidi-font-family:"Times New Roman"'>SOLUTION<br /> I -</span></b><span style='font-size:7.0pt;mso-bidi-font-family:"Times New Roman"'> <br /> </span><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Dissolve<br /> 13.61 g of <i>potassium <span class=SpellE>dihydrogen</span> phosphate </i>in<br /> sufficient <i>water </i>to produce 1000 ml.</span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:7.0pt;mso-bidi-font-family:"Times New Roman"'>SOLUTION<br /> II -</span></b><span style='font-size:7.0pt;mso-bidi-font-family:"Times New Roman"'> <br /> </span><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Dissolve<br /> 35.81 g of <span class=SpellE><i>disodium</i></span><i> hydrogen phosphate </i>in<br /> sufficient <i>water </i>to produce 1000 ml.</span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Mix<br /> 96.4 ml of solution I with 3.6 ml of solution II.</span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Phosphate<br /> Buffer pH 6.5:</span></b><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman"'> Dissolve 60.5 g of <span class=SpellE><i>disodium</i></span></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><i><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>hydrogen<br /> phosphate </span></i><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>and<br /> 46 g of <i>potassium <span class=SpellE>dihydrogen</span> phosphate </i>in <i>water,<br /> </i>add 100 ml of <i>0.02 M <span class=SpellE>disodium</span> edentate </i>and<br /> 20 mg of <i>mercuric chloride </i>and dilute with <i>water </i>to produce I000<br /> ml.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Phosphate<br /> Buffer pH 6.8, Mixed:</span></b><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman"'> Dissolve 28.?0 g of <span class=SpellE><i>disodium</i></span><i> <br /> hydrogen phosphate </i>and 11.45 g of <i>potassium <span class=SpellE>dihydrogen</span> <br /> phosphate </i>in sufficient <i>water </i>to produce 1000 ml.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Phosphate<br /> Buffer pH 6.8, 0.2 M Mixed:</span></b><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman"'> Dissolve 13.872 g of <i>potassium <span class=SpellE>dihydrogen</span> <br /> phosphate </i>and 35.084 g of <span class=SpellE><i>disodium</i></span> <i>hydrogen<br /> phosphate </i>in sufficient <i>water </i>to produce 1000 ml. Store in a cold<br /> place.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Phosphate<br /> Buffer pH 7.0, Mixed:</span></b><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman"'> Dissolve 0.50 g of <i>anhydrous <span class=SpellE>disodium</span> <br /> hydrogen phosphate </i>0.301 g of <i>potassium</i></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><span class=SpellE><i><span style='font-size:9.0pt; mso-bidi-font-family:"Times New Roman"'>dihydrogen</span></i></span><i><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'> phosphate </span></i><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>in sufficient <i>water<br /> </i>to produce</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Phosphate<br /> Buffer pH 7.0 with <span class=SpellE>Azide</span>, Mixed:</span></b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'> To 1000 ml of a<br /> solution containing 1.8 per cent w/v of <span class=SpellE><i>disodium</i></span><i> <br /> hydrogen</i> <i>phosphate </i>and 2.3 per cent w/v of <i>sodium chloride, </i>add<br /> sufficient of a solution containing 0.78 per cent w/v of <i>sodium <span class=SpellE>dihydrogen</span> phosphate </i>and 2.3 per cent w/v of <i>sodium<br /> chloride </i>(about 280 ml) to produce a pH of 7.0. Dissolve sufficient<i> <br /> sodium <span class=SpellE>azide</span> </i>in the resulting solution to give a<br /> 0.02 per cent<i> </i>w/v solution.</span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Phosphate<br /> Buffer pH 7.0, 0.067 M Mixed:</span></b><span style='font-size:9.0pt; mso-bidi-font-family:"Times New Roman"'> Dissolve 3.532 g of <i>potassium <span class=SpellE>dihydrogen</span> phosphate </i>and 14.542 g of <span class=SpellE><i>disodium</i></span> <i>hydrogen phosphate </i>in sufficient <i>water<br /> </i>to produce 1000 ml.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Phosphate<br /> Buffer pH 7.0, 0.1 M Mixed; Phosphate Buffer pH 7.0, 0.1 M:</span></b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'> Dissolve 1.361<br /> g of <i>potassium <span class=SpellE>dihydrogen</span></i><b> </b><i>orthophosphate<br /> </i>in sufficient <i>water </i>to produce 100 ml and adjust the pH using 3.5<br /> per cent w/v solution of <span class=SpellE><i>disodium</i></span><b> </b><i>hydrogen<br /> orthophosphate.</i></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Phosphate<br /> Buffer pH 7.5:</span></b><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman"'> Dissolve 6.8 g of <i>potassium <span class=SpellE>dihydrogen</span> <br /> orthophosphate </i>and 1.56 g of <i>sodium hydroxide </i>in 900 ml of <i>water </i>adjust<br /> the pH 7.5 with <i>sodium hydroxide solution </i>and dilute with <i>water </i>to<br /> produce 1000 ml.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Phosphate<br /> Buffer pH 7.5, 0.2 M:</span></b><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman"'> Dissolve 27.2 g of <i>potassium <span class=SpellE>dihydrogen</span> <br /> phosphate </i>with 930 ml of <i>water </i>adjust the pH 7.5<i> </i>with 0.3 per<br /> cent w/v solution of <i>potassium hydroxide </i>and<i> </i>add sufficient <i>water<br /> </i>to produce 1000 ml.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Phosphate<br /> Buffer pH 7.5, 0.33 M Mixed:</span></b><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:7.0pt;mso-bidi-font-family:"Times New Roman"'>SOLUTION<br /> I -</span></b><span style='font-size:7.0pt;mso-bidi-font-family:"Times New Roman"'> <br /> </span><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Dissolve<br /> 119.3 I g of <span class=SpellE><i>disodium</i></span><i> hydrogen phosphate </i>in<br /> sufficient <i>water </i>to produce 1000 ml.</span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:7.0pt;mso-bidi-font-family:"Times New Roman"'>SOLUTION<br /> II -</span></b><span style='font-size:7.0pt;mso-bidi-font-family:"Times New Roman"'> <br /> </span><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Dissolve<br /> 45.36 g of <i>potassium <span class=SpellE>dihydrogen</span> phosphate </i>in<br /> sufficient <i>water </i>to produce 1000 ml.</span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Mix<br /> 85 ml of solution I and 15 ml of solution II and adjust the pH if necessary.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Phosphate<br /> Buffer pH 8.0, 0.02 M:</span></b><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman"'> Mix 50 ml of <i>0.2 </i></span><i><span style='font-size: 9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>M </span></i><i><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>potassium <span class=SpellE>dihydrogen</span> phosphate </span></i><span style='font-size: 9.0pt;mso-bidi-font-family:"Times New Roman"'>with 46.8 ml of <i>0.2 M sodium</i></span><i><span style='font-size:9.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'> <br /> </span></i><i><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>hydroxide<br /> </span></i><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>and<br /> add sufficient <i>water </i>to produce 500 ml.</span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Phosphate<br /> Buffer, 0.025 M Standard:</span></b><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman"'> Dissolve 3.40 g of <i>potassium <span class=SpellE>dihydrogen</span> <br /> phosphate </i>and 3.55 g of <i>anhydrous</i> <span class=SpellE><i>disodium</i></span><i> <br /> hydrogen phosphate, </i>both previously dried at </span><span style='font-size: 8.0pt;mso-bidi-font-family:"Times New Roman"'>1100</span><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'> to </span><span style='font-size:8.0pt;mso-bidi-font-family:"Times New Roman"'>1300 </span><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>for 2 hours, in<br /> sufficient <i>water </i>to produce 1000 ml.</span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Phosphate<br /> Buffer, 0.05 M:</span></b><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman"'> Dissolve 6.8 g of <i>potassium <span class=SpellE>dihydrogen</span> <br /> orthophosphate </i>in sufficient <i>water </i>to produce<i> </i>l000ml.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Saline,<br /> Phosphate-buffered:</span></b><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman"'> Dissolve 2.5 g of <i>sodium <span class=SpellE>dihydrogen</span> <br /> phosphate, </i>2.523 g of <span class=SpellE><i>disodium</i></span><i> hydrogen<br /> phosphate </i>and 8.2 g of <i>sodium chloride </i>in sufficient <i>water </i>to<i> <br /> </i>produce 1000 ml.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Saline<br /> pH 6.4, Phosphate-buffered:</span></b><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman"'> Dissolve 1.79g of <span class=SpellE><i>disodium</i></span><i> <br /> hydrogen phosphate, </i>1.36 g of <i>potassium <span class=SpellE>dihydrogen</span> <br /> phosphate </i>and 7.02 g of <i>sodium chloride </i>in sufficient <i>water </i>to<br /> produce 1000 ml.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>Saline<br /> pH 7.4, Phosphate-buffered:</span></b><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman"'> Dissolve 2.38 g of <span class=SpellE><i>disodium</i></span><i> <br /> hydrogen phosphate, </i>0.19 g of <i>potassium <span class=SpellE>dihydrogen</span> <br /> phosphate </i>and 8.0 g of <i>sodium chloride </i>in sufficient <i>water </i>to<i> <br /> </i>produce 1000 ml. Adjust the pH, if necessary.</span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><span class=SpellE><b><span style='font-size:9.0pt; mso-bidi-font-family:"Times New Roman"'>Tris</span></b></span><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>-Acetate Buffer<br /> pH 8.5:</span></b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'> <br /> Dissolve 0.294 g of <i>calcium chloride </i>and 12.11 g of <span class=SpellE><i>tris</i></span><i>(<span class=SpellE>hydroxymethyl</span>)<span class=SpellE>aminomethane</span> </i>in<br /> <i>water. </i>Adjust the pH with 5 <i>M acetic acid </i>and dilute to<i> </i>1000.0<br /> ml with <i>water.</i></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><span class=SpellE><b><span style='font-size:9.0pt; mso-bidi-font-family:"Times New Roman"'>Tris</span></b></span><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>-Chloride Buffer<br /> pH 7.4:</span></b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'> <br /> Dissolve 7.27 g of <span class=SpellE><i>tris</i></span><i>(<span class=SpellE>hydroxymethyl</span>)methylamine<br /> </i>and 5.27 g of <i>sodium</i> <i>chloride </i>adjust the pH, if necessary and<br /> dilute with <i>water </i>to produce 1000 ml.</span><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><span class=SpellE><b><span style='font-size:9.0pt; mso-bidi-font-family:"Times New Roman"'>Tris</span></b></span><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>(<span class=SpellE>hydroxymethyl</span>)<span class=SpellE>aminomethane</span> Buffer<br /> pH 7.4:</span></b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'> <br /> Dissolve 30.3 g of <span class=SpellE><i>tris</i></span><i>(<span class=SpellE>hydroxymethyl</span>)<span class=SpellE>aminimethane</span> </i>in approximately 200 ml of <i>water. </i>Add<br /> 183 ml of I <i>M hydrochloric acid. </i>Dilute to 500.0 ml with <i>water.</i></span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><b><i><span style='font-size:9.0pt;mso-bidi-font-family: "Times New Roman"'>NOTE </span></i></b><b><span style='font-size:9.0pt; mso-bidi-font-family:"Times New Roman"'>-</span></b><span style='font-size: 9.0pt;mso-bidi-font-family:"Times New Roman"'> <i>The pH is </i></span><span style='font-size:8.0pt;font-family:Arial;mso-bidi-font-family:"Times New Roman"'>7.<br /> 7-7.8 </span><i><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>at<br /> room temperature and </span></i><span style='font-size:8.0pt;font-family:Arial; mso-bidi-font-family:"Times New Roman"'>7.4 </span><i><span style='font-size: 9.0pt;mso-bidi-font-family:"Times New Roman"'>at 37°. This solution is stable<br /> for several months at 4°.</span></i><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><span class=SpellE><b><span style='font-size:9.0pt; mso-bidi-font-family:"Times New Roman"'>Tris</span></b></span><b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'>(<span class=SpellE>hydroxymethyl</span>)<span class=SpellE>aminomethane</span> Buffer<br /> pH 8.1:</span></b><span style='font-size:9.0pt;mso-bidi-font-family:"Times New Roman"'> <br /> Dissolve 2.9 g of <i>calcium chloride </i>with 400 ml of <span class=SpellE><i>tris</i></span><i>(<br /> <span class=SpellE>hydroxymethyl</span>)<span class=SpellE>aminomethane</span> <br /> solution </i>adjust the pH with] <i>M hydrochloric acid </i>and dilute with <i>water<br /> </i>to produce l000 ml.</span><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p> <br /> <p class=MsoNormal><o:p> </o:p></p> <br /> </div> <br /> </body> <br /> <br /> </html>http://scholarpharma.blogspot.com/2012/01/preparation-of-buffer-solutions_05.html0margipatel02@gmail.com (margipatel02@gmail.com)tag:blogger.com,1999:blog-8563020669307343167.post-2580297027735156591Mon, 02 Jan 2012 04:29:00 +00002012-01-01T20:29:45.928-08:00Regulatory GuidelinesRegulatory Guidelines<html xmlns:o="urn:schemas-microsoft-com:office:office" xmlns:w="urn:schemas-microsoft-com:office:word" xmlns="http://www.w3.org/TR/REC-html40"> <br /> <br /> <head> <br /> <meta http-equiv=Content-Type content="text/html; charset=windows-1252"> <br /> <meta name=ProgId content=Word.Document> <br /> <meta name=Generator content="Microsoft Word 11"> <br /> <meta name=Originator content="Microsoft Word 11"> <br /> <link rel=File-List href="Regulatory%20Guidelines_files/filelist.xml"> <br /> <title>Regulatory Guidelines</title> <br />  <br /> <style>  </style> <br />  <br /> </head> <br /> <br /> <body lang=EN-US link=blue vlink=purple style='tab-interval:.5in'> <br /> <br /> <div class=Section1> <br /> <p class=MsoNormal style='margin-top:19.2pt;margin-right:0in;margin-bottom: 6.0pt;margin-left:0in;line-height:10.0pt;mso-outline-level:2;background:white'><b><span style='font-size:8.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>Regulatory Guidelines<o:p></o:p></span></b></p> <br /> <p class=MsoNormal style='line-height:10.0pt'><span class=GramE><span style='font-size:8.0pt;font-family:Symbol;mso-ascii-font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>·</span><span style='font-size:8.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><span style='mso-spacerun:yes'> </span></span></span><span style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'><a href="http://pharmaguideline.blogspot.com/2011/02/iso.html"><span style='color:#38761D'>ISO Guidelines</span></a></span><span style='font-size: 8.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='line-height:10.0pt'><span class=GramE><span style='font-size:8.0pt;font-family:Symbol;mso-ascii-font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>·</span><span style='font-size:8.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><span style='mso-spacerun:yes'> </span></span></span><span style='font-size:8.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><a href="http://pharmaguideline.blogspot.com/2010/10/who.html"><span style='mso-bidi-font-size:12.0pt;color:#38761D'>WHO Guidelines</span></a><o:p></o:p></span></p> <br /> <p class=MsoNormal style='line-height:10.0pt'><span class=GramE><span style='font-size:8.0pt;font-family:Symbol;mso-ascii-font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>·</span><span style='font-size:8.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><span style='mso-spacerun:yes'> </span></span></span><span style='font-size:8.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><a href="http://pharmaguideline.blogspot.com/2010/10/usfda.html"><span style='mso-bidi-font-size:12.0pt;color:#38761D'>US-FDA Guidelines</span></a><o:p></o:p></span></p> <br /> <p class=MsoNormal style='line-height:10.0pt'><span class=GramE><span style='font-size:8.0pt;font-family:Symbol;mso-ascii-font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>·</span><span style='font-size:8.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><span style='mso-spacerun:yes'> </span></span></span><span style='font-size:8.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><a href="http://pharmaguideline.blogspot.com/2010/10/ich.html"><span style='mso-bidi-font-size:12.0pt;color:#38761D'>ICH Guidelines</span></a><o:p></o:p></span></p> <br /> <p class=MsoNormal style='line-height:10.0pt'><span class=GramE><span style='font-size:8.0pt;font-family:Symbol;mso-ascii-font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>·</span><span style='font-size:8.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><span style='mso-spacerun:yes'> </span></span></span><span style='font-size:8.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><a href="http://pharmaguideline.blogspot.com/2010/10/mhra.html"><span style='mso-bidi-font-size:12.0pt;color:#38761D'>MHRA-UK Guidelines</span></a><o:p></o:p></span></p> <br /> <p class=MsoNormal style='line-height:10.0pt'><span class=GramE><span style='font-size:8.0pt;font-family:Symbol;mso-ascii-font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>·</span><span style='font-size:8.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><span style='mso-spacerun:yes'> </span></span></span><span style='font-size:8.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><a href="http://pharmaguideline.blogspot.com/2010/10/mcc.html"><span style='mso-bidi-font-size:12.0pt;color:#38761D'>MCC Guidelines -South Africa</span></a><o:p></o:p></span></p> <br /> <p class=MsoNormal style='line-height:10.0pt'><span class=GramE><span style='font-size:8.0pt;font-family:Symbol;mso-ascii-font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>·</span><span style='font-size:8.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><span style='mso-spacerun:yes'> </span></span></span><span style='font-size:8.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><a href="http://pharmaguideline.blogspot.com/2010/10/tga.html"><span style='mso-bidi-font-size:12.0pt;color:#38761D'>TGA Guidelines-Australia</span></a><o:p></o:p></span></p> <br /> <p class=MsoNormal style='line-height:10.0pt'><span class=GramE><span style='font-size:8.0pt;font-family:Symbol;mso-ascii-font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>·</span><span style='font-size:8.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><span style='mso-spacerun:yes'> </span></span></span><span style='font-size:8.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><a href="http://www.mcaz.co.zw/trials/MCAZ%20Amendment%20guidelines.pdf" target="_blank"><span style='mso-bidi-font-size:12.0pt;color:#38761D'>MCA<br /> Guidelines-Zimbabwe</span></a><o:p></o:p></span></p> <br /> <p class=MsoNormal style='line-height:10.0pt'><span class=GramE><span style='font-size:8.0pt;font-family:Symbol;mso-ascii-font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>·</span><span style='font-size:8.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><span style='mso-spacerun:yes'> </span></span></span><span style='font-size:8.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><a href="http://pharmaguideline.blogspot.com/2010/10/schedule-m.html"><span style='mso-bidi-font-size:12.0pt;color:#38761D'>Schedule M-India</span></a><o:p></o:p></span></p> <br /> <p class=MsoNormal style='line-height:10.0pt'><span class=GramE><span style='font-size:8.0pt;font-family:Symbol;mso-ascii-font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>·</span><span style='font-size:8.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><span style='mso-spacerun:yes'> </span></span></span><span style='font-size:8.0pt;mso-bidi-font-size:12.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'><a href="http://pharmaguideline.blogspot.com/2010/10/europe.html"><span style='color:#38761D'>European Guidelines</span></a></span><span style='font-size:8.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='line-height:10.0pt'><span class=GramE><span style='font-size:8.0pt;font-family:Symbol;mso-ascii-font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>·</span><span style='font-size:8.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><span style='mso-spacerun:yes'> </span></span></span><span style='font-size:8.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><a href="http://pharmaguideline.blogspot.com/2010/10/newzeland.html"><span style='mso-bidi-font-size:12.0pt;color:#38761D'>MEDSAFE Guidelines -<span class=SpellE>Newzeland</span></span></a><o:p></o:p></span></p> <br /> <p class=MsoNormal style='line-height:10.0pt'><span class=GramE><span style='font-size:8.0pt;font-family:Symbol;mso-ascii-font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>·</span><span style='font-size:8.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><span style='mso-spacerun:yes'> </span></span></span><span style='font-size:8.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><a href="http://pharmaguideline.blogspot.com/2010/10/gcc.html"><span style='mso-bidi-font-size:12.0pt;color:#38761D'>GCC Guidelines -Gulf</span></a><o:p></o:p></span></p> <br /> <p class=MsoNormal style='line-height:10.0pt'><span class=GramE><span style='font-size:8.0pt;font-family:Symbol;mso-ascii-font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>·</span><span style='font-size:8.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><span style='mso-spacerun:yes'> </span></span></span><span style='font-size:8.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><a href="http://pharmaguideline.blogspot.com/2010/10/japan.html"><span style='mso-bidi-font-size:12.0pt;color:#38761D'>PDMA Guidelines -Japan</span></a><o:p></o:p></span></p> <br /> <p class=MsoNormal style='line-height:10.0pt'><span class=GramE><span style='font-size:8.0pt;font-family:Symbol;mso-ascii-font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>·</span><span style='font-size:8.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><span style='mso-spacerun:yes'> </span></span></span><span style='font-size:8.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><a href="http://pharmaguideline.blogspot.com/2010/10/pandrh.html"><span style='mso-bidi-font-size:12.0pt;color:#38761D'>PANDRH Guidelines -American</span></a><o:p></o:p></span></p> <br /> <p class=MsoNormal style='line-height:10.0pt'><span class=GramE><span style='font-size:8.0pt;font-family:Symbol;mso-ascii-font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>·</span><span style='font-size:8.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><span style='mso-spacerun:yes'> </span></span></span><span style='font-size:8.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><a href="http://pharmaguideline.blogspot.com/2010/10/pics-pharmaceutical-inspection.html"><span style='mso-bidi-font-size:12.0pt;color:#38761D'>PIC/S Guidelines</span></a><o:p></o:p></span></p> <br /> <p class=MsoNormal style='line-height:10.0pt'><span class=GramE><span style='font-size:8.0pt;font-family:Symbol;mso-ascii-font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>·</span><span style='font-size:8.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><span style='mso-spacerun:yes'> </span></span></span><span style='font-size:8.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><a href="http://pharmaguideline.blogspot.com/2010/10/ipeq.html"><span style='mso-bidi-font-size:12.0pt;color:#38761D'>IPEQ Guidelines</span></a><o:p></o:p></span></p> <br /> <p class=MsoNormal style='line-height:10.0pt'><span class=GramE><span style='font-size:8.0pt;font-family:Symbol;mso-ascii-font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>·</span><span style='font-size:8.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><span style='mso-spacerun:yes'> </span></span></span><span style='font-size:8.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><a href="http://pharmaguideline.blogspot.com/2010/10/drugs-cosmetics-act.html"><span style='mso-bidi-font-size:12.0pt;color:#38761D'>Drugs & Cosmetics Act-India</span></a><o:p></o:p></span></p> <br /> <p class=MsoNormal style='line-height:10.0pt'><span class=GramE><span style='font-size:8.0pt;font-family:Symbol;mso-ascii-font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>·</span><span style='font-size:8.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><span style='mso-spacerun:yes'> </span></span></span><span style='font-size:8.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><a href="http://apic.cefic.org/publications/publications.html" target="_blank"><span style='mso-bidi-font-size:12.0pt;color:#38761D'>APIC<br /> Guidelines</span></a><o:p></o:p></span></p> <br /> <p class=MsoNormal style='line-height:10.0pt'><span class=GramE><span style='font-size:8.0pt;font-family:Symbol;mso-ascii-font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>·</span><span style='font-size:8.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><span style='mso-spacerun:yes'> </span></span></span><span style='font-size:8.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><a href="http://ec.europa.eu/health/documents/eudralex/vol-4/index_en.htm" target="_blank"><span style='mso-bidi-font-size:12.0pt;color:#38761D'>EU<br /> Guidelines</span></a><o:p></o:p></span></p> <br /> <p class=MsoNormal><o:p> </o:p></p> <br /> </div> <br /> </body> <br /> <br /> </html>http://scholarpharma.blogspot.com/2012/01/regulatory-guidelines.html0margipatel02@gmail.com (margipatel02@gmail.com)tag:blogger.com,1999:blog-8563020669307343167.post-6734221425367812376Mon, 02 Jan 2012 04:26:00 +00002012-01-01T20:26:26.263-08:00ICH GuidelinesICH Guidelines<html xmlns:o="urn:schemas-microsoft-com:office:office" xmlns:w="urn:schemas-microsoft-com:office:word" xmlns="http://www.w3.org/TR/REC-html40"> <br /> <br /> <head> <br /> <meta http-equiv=Content-Type content="text/html; charset=windows-1252"> <br /> <meta name=ProgId content=Word.Document> <br /> <meta name=Generator content="Microsoft Word 11"> <br /> <meta name=Originator content="Microsoft Word 11"> <br /> <link rel=File-List href="ICH%20Guidelines_files/filelist.xml"> <br /> <title>ICH Guidelines</title> <br />  <br /> <style>  </style> <br />  <br /> </head> <br /> <br /> <body lang=EN-US link=blue vlink=purple style='tab-interval:.5in'> <br /> <br /> <div class=Section1> <br /> <p class=MsoNormal style='line-height:13.2pt;mso-outline-level:3'><b><span style='font-size:11.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>ICH Guidelines<o:p></o:p></span></b></p> <br /> <p class=MsoNormal style='margin-bottom:12.0pt;line-height:15.6pt'><b><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>International Conference<br /> on <span class=SpellE>Harmonisation</span></span></b><span style='font-size: 9.0pt;mso-bidi-font-size:12.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'> (<b>ICH</b>) is a <span class=SpellE>commety</span> that<br /> provides the pharmaceutical guidelines for industries.</span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='margin-bottom:12.0pt;line-height:15.6pt'><span class=GramE><span style='font-size:9.0pt;font-family:Symbol;mso-ascii-font-family: Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>·</span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><span style='mso-spacerun:yes'> </span></span></span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><a href="http://www.ich.org/products/guidelines/quality/article/quality-guidelines.html" target="_blank"><span style='mso-bidi-font-size:12.0pt;color:red'>Quality<br /> Guidelines</span></a><o:p></o:p></span></p> <br /> <p class=MsoNormal style='margin-bottom:12.0pt;line-height:15.6pt'><span class=GramE><span style='font-size:9.0pt;font-family:Symbol;mso-ascii-font-family: Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>·</span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><span style='mso-spacerun:yes'> </span></span></span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><a href="http://www.ich.org/products/guidelines/efficacy/article/efficacy-guidelines.html" target="_blank"><span style='mso-bidi-font-size:12.0pt;color:red'>Efficacy<br /> Guidelines</span></a><br> <br /> <br> <br /> </span><span style='font-size:9.0pt;font-family:Symbol;mso-ascii-font-family: Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>·</span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><span style='mso-spacerun:yes'> </span><a href="http://www.ich.org/products/guidelines/safety/article/safety-guidelines.html" target="_blank"><span style='mso-bidi-font-size:12.0pt;color:red'>Safety<br /> Guidelines</span></a><o:p></o:p></span></p> <br /> <p class=MsoNormal style='line-height:15.6pt'><span class=GramE><span style='font-size:9.0pt;font-family:Symbol;mso-ascii-font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>·</span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><span style='mso-spacerun:yes'> </span></span></span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><a href="http://www.ich.org/products/guidelines/multidisciplinary/article/multidisciplinary-guidelines.html" target="_blank"><span style='mso-bidi-font-size:12.0pt;color:red'>Multidisciplinary<br /> Guidelines</span></a><o:p></o:p></span></p> <br /> <p class=MsoNormal><o:p> </o:p></p> <br /> </div> <br /> </body> <br /> <br /> </html>http://scholarpharma.blogspot.com/2012/01/ich-guidelines.html0margipatel02@gmail.com (margipatel02@gmail.com)tag:blogger.com,1999:blog-8563020669307343167.post-6453626647348287094Mon, 02 Jan 2012 04:23:00 +00002012-01-01T20:23:16.873-08:00WHO GuidelinesWHO Guidelines<html xmlns:o="urn:schemas-microsoft-com:office:office" xmlns:w="urn:schemas-microsoft-com:office:word" xmlns="http://www.w3.org/TR/REC-html40"> <br /> <br /> <head> <br /> <meta http-equiv=Content-Type content="text/html; charset=windows-1252"> <br /> <meta name=ProgId content=Word.Document> <br /> <meta name=Generator content="Microsoft Word 11"> <br /> <meta name=Originator content="Microsoft Word 11"> <br /> <link rel=File-List href="WHO%20Guidelines_files/filelist.xml"> <br /> <title>WHO Guidelines</title> <br />  <br /> <style>  </style> <br />  <br /> </head> <br /> <br /> <body lang=EN-US link=blue vlink=purple style='tab-interval:.5in'> <br /> <br /> <div class=Section1> <br /> <p class=MsoNormal style='line-height:13.2pt;mso-outline-level:3'><span class=GramE><b><span style='font-size:11.0pt;font-family:Verdana;mso-bidi-font-family: "Times New Roman";color:#333333'>WHO</span></b></span><b><span style='font-size:11.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'> Guidelines<o:p></o:p></span></b></p> <br /> <p class=MsoNormal style='margin-bottom:12.0pt;line-height:15.6pt'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>World health organization (<span class=GramE>WHO</span>) provide<br /> the GMP guidelines for pharmaceuticals. These guidelines are followed through<br /> the world.<br> <br /> These guidelines cover all the pharmaceutical topics as<span class=GramE>:</span><br> <br /> 1. Process validation<br> <br /> 2. <span class=GramE>Cleaning validation<br> <br /> 3.</span> <span class=GramE>Analytical method validation<br> <br /> 4.</span> <span class=GramE>DQ, IQ, OQ, PQ of equipments<br> <br /> 5.</span> <span class=GramE>Water system validation<br> <br /> 6.</span> <span class=GramE>HVAC validation<br> <br /> 7.</span> <span class=GramE>Computer system validation<br> <br /> 8.</span> <span class=GramE>Market complaint handling<br> <br /> 9.</span> Product recalls<br> <br /> 10 Stability studies and may more...<br> <br /> <br> <br /> Following are the general guidelines of WHO.<br> <br /> <br> <br /> <br style='mso-special-character:line-break'> <br /> <![if !supportLineBreakNewLine]><br style='mso-special-character:line-break'> <br /> <![endif]><o:p></o:p></span></p> <br /> <p class=MsoNormal style='margin-bottom:12.0pt;line-height:15.6pt'><span class=GramE><span style='font-size:9.0pt;font-family:Symbol;mso-ascii-font-family: Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>·</span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><span style='mso-spacerun:yes'> </span></span></span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><a href="http://www.who.int/medicines/areas/quality_safety/quality_assurance/QualityAssurancePharmVol2.pdf" target="_blank"><span style='mso-bidi-font-size:12.0pt;color:red'>General</span></a><br> <br /> <br> <br /> <br> <br /> <br> <br /> <br> <br /> <br> <br /> <br> <br /> <br style='mso-special-character:line-break'> <br /> <![if !supportLineBreakNewLine]><br style='mso-special-character:line-break'> <br /> <![endif]><o:p></o:p></span></p> <br /> <p class=MsoNormal style='margin-bottom:12.0pt;line-height:15.6pt'><span class=GramE><span style='font-size:9.0pt;font-family:Symbol;mso-ascii-font-family: Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>·</span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><span style='mso-spacerun:yes'> </span></span></span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><a href="http://whqlibdoc.who.int/trs/WHO_TRS_908.pdf#page=%2046" target="_blank"><span style='mso-bidi-font-size:12.0pt;color:red'>Volume 2, 2nd<br /> updated edition</span></a><br> <br /> <br> <br /> <br> <br /> <br> <br /> <br> <br /> <br> <br /> <br> <br /> WHO guidelines for Active Pharmaceutical Ingredients<br> <br /> <br> <br /> <br style='mso-special-character:line-break'> <br /> <![if !supportLineBreakNewLine]><br style='mso-special-character:line-break'> <br /> <![endif]><o:p></o:p></span></p> <br /> <p class=MsoNormal style='line-height:15.6pt'><span class=GramE><span style='font-size:9.0pt;font-family:Symbol;mso-ascii-font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'>·</span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><span style='mso-spacerun:yes'> </span></span></span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><a href="http://whqlibdoc.who.int/trs/WHO_TRS_957_eng.pdf#page=144%3E%3Cspan%20style=" target="_blank"><span style='mso-bidi-font-size:12.0pt;color:#38761D'>API </span></a> <br> <br /> <br> <br /> <br> <br /> <br> <br /> <br> <br /> <b>New TRS</b><br> <br /> <b><br> <br /> </b><br> <br /> <a href="http://www.who.int/bloodproducts/publications/GMP_Bloodestablishments.pdf"><span style='mso-bidi-font-size:12.0pt;color:#38761D'>WHO Technical Report Series<br /> 961, 2011</span></a><o:p></o:p></span></p> <br /> <p class=MsoNormal style='line-height:15.6pt;mso-outline-level:3'><b><span style='font-size:13.5pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>44th report<o:p></o:p></span></b></p> <br /> <p class=MsoNormal style='line-height:15.6pt;mso-outline-level:3'><span style='font-family:Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'><a href="http://www.who.int/medicines/publications/TRS957_2010.pdf" target="_blank"><span style='color:#38761D'>English</span></a></span><span style='font-size:13.5pt; font-family:Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-size:9.0pt; font-family:Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>WHO<br /> Technical Report Series 957, 2010<o:p></o:p></span></p> <br /> <p class=MsoNormal style='line-height:15.6pt;mso-outline-level:3'><b><span style='font-size:13.5pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>43rd report<o:p></o:p></span></b></p> <br /> <ul type=disc> <li class=MsoNormal style='color:#333333;mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;line-height:15.6pt;mso-list:l3 level1 lfo1;tab-stops:list .5in'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"'><a href="http://www.who.int/medicines/publications/pharmprep/pdf_trs953.pdf"><span style='mso-bidi-font-size:12.0pt;color:#38761D'>English</span><span style='color:#38761D'><br> <br /> </span><span class=SpellE><span style='mso-bidi-font-size:12.0pt; color:#38761D'>pdf</span></span><span style='mso-bidi-font-size:12.0pt; color:#38761D'>, 999kb</span></a><br> <br /> </span><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;font-family: Verdana;mso-bidi-font-family:"Times New Roman"'>WHO Technical Report<br /> Series 953, 2009</span><span style='font-size:9.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></li> </ul> <br /> <p class=MsoNormal style='line-height:15.6pt;mso-outline-level:3'><b><span style='font-size:13.5pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>42nd report<o:p></o:p></span></b></p> <br /> <ul type=disc> <li class=MsoNormal style='color:#333333;mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;line-height:15.6pt;mso-list:l7 level1 lfo2;tab-stops:list .5in'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"'><a href="http://www.who.int/medicines/publications/pharmprep/OMS_TRS_948.pdf" target="_blank"><span style='mso-bidi-font-size:12.0pt;color:#38761D'>English</span><span style='color:#38761D'><br> <br /> </span><span class=SpellE><span style='mso-bidi-font-size:12.0pt; color:#38761D'>pdf</span></span><span style='mso-bidi-font-size:12.0pt; color:#38761D'>, 593kb</span></a><br> <br /> </span><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;font-family: Verdana;mso-bidi-font-family:"Times New Roman"'>WHO Technical Report<br /> Series 948, 2008</span><span style='font-size:9.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></li> </ul> <br /> <p class=MsoNormal style='line-height:15.6pt;mso-outline-level:3'><b><span style='font-size:13.5pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>41st report<o:p></o:p></span></b></p> <br /> <ul type=disc> <li class=MsoNormal style='color:#333333;mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;line-height:15.6pt;mso-list:l11 level1 lfo3;tab-stops:list .5in'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"'><a href="http://www.who.int/medicines/publications/pharmprep/TRS943_PharmPrep.pdf" target="_blank"><span style='mso-bidi-font-size:12.0pt;color:#38761D'>English</span><span style='color:#38761D'><br> <br /> </span><span class=SpellE><span style='mso-bidi-font-size:12.0pt; color:#38761D'>pdf</span></span><span style='mso-bidi-font-size:12.0pt; color:#38761D'>, 1.22Mb</span></a><br> <br /> </span><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;font-family: Verdana;mso-bidi-font-family:"Times New Roman"'>WHO Technical Report<br /> Series 943, 2007</span><span style='font-size:9.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></li> </ul> <br /> <p class=MsoNormal style='line-height:15.6pt;mso-outline-level:3'><b><span style='font-size:13.5pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>40th report<o:p></o:p></span></b></p> <br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-size:9.0pt; font-family:Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>WHO<br /> Technical Report Series 937, 2006<o:p></o:p></span></p> <br /> <ul type=disc> <li class=MsoNormal style='color:#333333;mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;line-height:15.6pt;mso-list:l8 level1 lfo4;tab-stops:list .5in'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"'><a href="http://whqlibdoc.who.int/trs/WHO_TRS_937_eng.pdf" target="_blank"><span style='mso-bidi-font-size:12.0pt;color:#38761D'>English [<span class=SpellE>pdf</span> 2.08Mb]</span></a><o:p></o:p></span></li> </ul> <br /> <p class=MsoNormal style='line-height:15.6pt;mso-outline-level:3'><b><span style='font-size:13.5pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>39th report<o:p></o:p></span></b></p> <br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-size:9.0pt; font-family:Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>WHO<br /> Technical Report Series 929, 2005<o:p></o:p></span></p> <br /> <ul type=disc> <li class=MsoNormal style='color:#333333;mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;line-height:15.6pt;mso-list:l4 level1 lfo5;tab-stops:list .5in'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"'><a href="http://whqlibdoc.who.int/trs/WHO_TRS_929_eng.pdf" target="_blank"><span style='mso-bidi-font-size:12.0pt;color:#38761D'>English [1.21Mb]</span></a><o:p></o:p></span></li> </ul> <br /> <p class=MsoNormal style='line-height:15.6pt;mso-outline-level:3'><b><span style='font-size:13.5pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>38th report<o:p></o:p></span></b></p> <br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-size:9.0pt; font-family:Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>WHO<br /> Technical Report Series 917, 2003<o:p></o:p></span></p> <br /> <ul type=disc> <li class=MsoNormal style='color:#333333;mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;line-height:15.6pt;mso-list:l2 level1 lfo6;tab-stops:list .5in'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"'><a href="http://whqlibdoc.who.int/trs/WHO_TRS_917.pdf" target="_blank"><span style='mso-bidi-font-size:12.0pt;color:#38761D'>English [<span class=SpellE>pdf</span> 386kb]</span></a><o:p></o:p></span></li> </ul> <br /> <p class=MsoNormal style='line-height:15.6pt;mso-outline-level:3'><b><span style='font-size:13.5pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>37th report<o:p></o:p></span></b></p> <br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-size:9.0pt; font-family:Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>WHO<br /> Technical Report Series 908, 2003<o:p></o:p></span></p> <br /> <ul type=disc> <li class=MsoNormal style='color:#333333;mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;line-height:15.6pt;mso-list:l1 level1 lfo7;tab-stops:list .5in'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"'><a href="http://whqlibdoc.who.int/trs/WHO_TRS_908.pdf" target="_blank"><span style='mso-bidi-font-size:12.0pt;color:#38761D'>English [<span class=SpellE>pdf</span> 632kb]</span></a><o:p></o:p></span></li> </ul> <br /> <p class=MsoNormal style='line-height:15.6pt;mso-outline-level:3'><b><span style='font-size:13.5pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>36th report<o:p></o:p></span></b></p> <br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-size:9.0pt; font-family:Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>WHO<br /> Technical Report Series 902, 2002<o:p></o:p></span></p> <br /> <ul type=disc> <li class=MsoNormal style='color:#333333;mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;line-height:15.6pt;mso-list:l9 level1 lfo8;tab-stops:list .5in'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"'><a href="http://whqlibdoc.who.int/trs/WHO_TRS_902.pdf" target="_blank"><span style='mso-bidi-font-size:12.0pt;color:#38761D'>English [<span class=SpellE>pdf</span> 1Mb]</span></a><o:p></o:p></span></li> </ul> <br /> <p class=MsoNormal style='line-height:15.6pt;mso-outline-level:3'><b><span style='font-size:13.5pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>35th report<o:p></o:p></span></b></p> <br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-size:9.0pt; font-family:Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>WHO<br /> Technical Report Series 885, 1999<o:p></o:p></span></p> <br /> <ul type=disc> <li class=MsoNormal style='color:#333333;mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;line-height:15.6pt;mso-list:l0 level1 lfo9;tab-stops:list .5in'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"'><a href="http://whqlibdoc.who.int/trs/WHO_TRS_885.pdf" target="_blank"><span style='mso-bidi-font-size:12.0pt;color:#38761D'>English [<span class=SpellE>pdf</span> 7Mb]</span></a><o:p></o:p></span></li> </ul> <br /> <p class=MsoNormal style='line-height:15.6pt;mso-outline-level:3'><b><span style='font-size:13.5pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>34th report<o:p></o:p></span></b></p> <br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-size:9.0pt; font-family:Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>WHO<br /> Technical Report Series 863, 1996<o:p></o:p></span></p> <br /> <ul type=disc> <li class=MsoNormal style='color:#333333;mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;line-height:15.6pt;mso-list:l5 level1 lfo10;tab-stops:list .5in'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"'><a href="http://whqlibdoc.who.int/trs/WHO_TRS_863_%28p1-p98%29.pdf" target="_blank"><span style='mso-bidi-font-size:12.0pt;color:#38761D'>English<br /> Part 1 [<span class=SpellE>pdf</span> 3.8Mb]</span></a></span><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman"'> </span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></li> <li class=MsoNormal style='color:#333333;mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;line-height:15.6pt;mso-list:l5 level1 lfo10;tab-stops:list .5in'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"'><a href="http://whqlibdoc.who.int/trs/WHO_TRS_863_%28p99-p194%29.pdf" target="_blank"><span style='mso-bidi-font-size:12.0pt;color:#38761D'>English<br /> Part 2 [<span class=SpellE>pdf</span> 4Mb]</span></a><o:p></o:p></span></li> </ul> <br /> <p class=MsoNormal style='line-height:15.6pt;mso-outline-level:3'><b><span style='font-size:13.5pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>33rd report<o:p></o:p></span></b></p> <br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-size:9.0pt; font-family:Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>WHO<br /> Technical Report Series 834, 1993<o:p></o:p></span></p> <br /> <ul type=disc> <li class=MsoNormal style='color:#333333;mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;line-height:15.6pt;mso-list:l10 level1 lfo11;tab-stops:list .5in'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"'><a href="http://whqlibdoc.who.int/trs/WHO_TRS_834.pdf" target="_blank"><span style='mso-bidi-font-size:12.0pt;color:#38761D'>English [<span class=SpellE>pdf</span> 1.5Mb]</span></a><o:p></o:p></span></li> </ul> <br /> <p class=MsoNormal style='line-height:15.6pt;mso-outline-level:3'><b><span style='font-size:13.5pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>32nd report<o:p></o:p></span></b></p> <br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-size:9.0pt; font-family:Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>WHO<br /> Technical Report Series 823, 1992<o:p></o:p></span></p> <br /> <ul type=disc> <li class=MsoNormal style='color:#333333;mso-margin-top-alt:auto;mso-margin-bottom-alt: auto;line-height:15.6pt;mso-list:l6 level1 lfo12;tab-stops:list .5in'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"'><a href="http://whqlibdoc.who.int/trs/WHO_TRS_823.pdf" target="_blank"><span style='mso-bidi-font-size:12.0pt;color:#38761D'>English [<span class=SpellE>pdf</span> 6.4Mb]</span></a> <o:p></o:p></span></li> </ul> <br /> <p class=MsoNormal style='margin-bottom:12.0pt;line-height:15.6pt'><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p> </o:p></span></p> <br /> <p class=MsoNormal style='margin-bottom:12.0pt;line-height:15.6pt'><span class=GramE><span style='font-size:9.0pt;font-family:Symbol;mso-ascii-font-family: Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>·</span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><span style='mso-spacerun:yes'> </span></span></span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><a href="http://whqlibdoc.who.int/trs/WHO_TRS_908.pdf" target="_blank"><span style='mso-bidi-font-size:12.0pt;color:#38761D'>Risk<br /> analysis</span></a><br> <br /> <br> <br /> <br style='mso-special-character:line-break'> <br /> <![if !supportLineBreakNewLine]><br style='mso-special-character:line-break'> <br /> <![endif]><o:p></o:p></span></p> <br /> <p class=MsoNormal style='margin-bottom:12.0pt;line-height:15.6pt'><span class=GramE><span style='font-size:9.0pt;font-family:Symbol;mso-ascii-font-family: Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>·</span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><span style='mso-spacerun:yes'> </span></span></span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><a href="http://mednet3.who.int/prequal/trainingresources/pq_pres/gmptraining/GMPBasicTraining.htm" target="_blank"><span style='mso-bidi-font-size:12.0pt;color:#38761D'>Training<br /> materials</span></a><br> <br /> <br> <br /> <br style='mso-special-character:line-break'> <br /> <![if !supportLineBreakNewLine]><br style='mso-special-character:line-break'> <br /> <![endif]><o:p></o:p></span></p> <br /> <p class=MsoNormal style='margin-bottom:12.0pt;line-height:15.6pt'><span class=GramE><span style='font-size:9.0pt;font-family:Symbol;mso-ascii-font-family: Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>·</span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><span style='mso-spacerun:yes'> </span></span></span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><a href="http://mednet3.who.int/prequal/trainingresources/pq_pres/gmptrainsuplmt/suptrainingmodulesgmp.htm" target="_blank"><span style='mso-bidi-font-size:12.0pt;color:#38761D'>An<br /> introduction, resource and study pack for trainers</span></a><br> <br /> <br> <br /> <br style='mso-special-character:line-break'> <br /> <![if !supportLineBreakNewLine]><br style='mso-special-character:line-break'> <br /> <![endif]><o:p></o:p></span></p> <br /> <p class=MsoNormal style='margin-bottom:12.0pt;line-height:15.6pt'><span class=GramE><span style='font-size:9.0pt;font-family:Symbol;mso-ascii-font-family: Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>·</span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><span style='mso-spacerun:yes'> </span></span></span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><a href="http://www.who.int/bloodproducts/gmp/en/" target="_blank"><span style='mso-bidi-font-size:12.0pt;color:#38761D'>Blood and<br /> Biological Products</span></a><br> <br /> <br> <br /> <br style='mso-special-character:line-break'> <br /> <![if !supportLineBreakNewLine]><br style='mso-special-character:line-break'> <br /> <![endif]><o:p></o:p></span></p> <br /> <p class=MsoNormal style='margin-bottom:12.0pt;line-height:15.6pt'><span class=GramE><span style='font-size:9.0pt;font-family:Symbol;mso-ascii-font-family: Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>·</span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><span style='mso-spacerun:yes'> </span></span></span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><a href="http://whqlibdoc.who.int/hq/2006/WHO_IVB_05.24_eng.pdf" target="_blank"><span style='mso-bidi-font-size:12.0pt;color:#38761D'>Radio<br /> Pharmaceuticals</span></a><br> <br /> <br> <br /> <br style='mso-special-character:line-break'> <br /> <![if !supportLineBreakNewLine]><br style='mso-special-character:line-break'> <br /> <![endif]><o:p></o:p></span></p> <br /> <p class=MsoNormal style='margin-bottom:12.0pt;line-height:15.6pt'><span class=GramE><span style='font-size:9.0pt;font-family:Symbol;mso-ascii-font-family: Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>·</span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><span style='mso-spacerun:yes'> </span></span></span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><a href="http://whqlibdoc.who.int/hq/1997/WHO_VSQ_97.01.pdf" target="_blank"><span style='mso-bidi-font-size:12.0pt;color:#38761D'>Further<br /> References</span></a><br> <br /> <br> <br /> <br> <br /> <br> <br /> <br> <br /> </span><b><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;font-family: Verdana;mso-bidi-font-family:"Times New Roman";color:red'>Also Read:</span></b><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><br style='mso-special-character:line-break'> <br /> <![if !supportLineBreakNewLine]><br style='mso-special-character:line-break'> <br /> <![endif]><o:p></o:p></span></p> <br /> <p class=MsoNormal style='margin-bottom:12.0pt;line-height:15.6pt'><span class=GramE><span style='font-size:9.0pt;font-family:Symbol;mso-ascii-font-family: Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>·</span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><span style='mso-spacerun:yes'> </span></span></span><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#333333'><a href="http://pharmaguideline.blogspot.com/2011/02/iso.html"><span style='color:#307F0D'>ISO Guidelines</span></a></span><span style='font-size: 9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'><br> <br /> <br style='mso-special-character:line-break'> <br /> <![if !supportLineBreakNewLine]><br style='mso-special-character:line-break'> <br /> <![endif]><o:p></o:p></span></p> <br /> <p class=MsoNormal style='margin-bottom:12.0pt;line-height:15.6pt'><span class=GramE><span style='font-size:9.0pt;font-family:Symbol;mso-ascii-font-family: Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>·</span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><span style='mso-spacerun:yes'> </span></span></span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><a href="http://pharmaguideline.blogspot.com/2010/10/usfda.html"><span style='mso-bidi-font-size:12.0pt;color:#307F0D'>US-FDA Guidelines</span></a><br> <br /> <br style='mso-special-character:line-break'> <br /> <![if !supportLineBreakNewLine]><br style='mso-special-character:line-break'> <br /> <![endif]><o:p></o:p></span></p> <br /> <p class=MsoNormal style='margin-bottom:12.0pt;line-height:15.6pt'><span class=GramE><span style='font-size:9.0pt;font-family:Symbol;mso-ascii-font-family: Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>·</span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><span style='mso-spacerun:yes'> </span></span></span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><a href="http://pharmaguideline.blogspot.com/2010/10/ich.html"><span style='mso-bidi-font-size:12.0pt;color:#307F0D'>ICH Guidelines</span></a><br> <br /> <br style='mso-special-character:line-break'> <br /> <![if !supportLineBreakNewLine]><br style='mso-special-character:line-break'> <br /> <![endif]><o:p></o:p></span></p> <br /> <p class=MsoNormal style='margin-bottom:12.0pt;line-height:15.6pt'><span class=GramE><span style='font-size:9.0pt;font-family:Symbol;mso-ascii-font-family: Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>·</span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><span style='mso-spacerun:yes'> </span></span></span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><a href="http://pharmaguideline.blogspot.com/2010/10/mhra.html"><span style='mso-bidi-font-size:12.0pt;color:#307F0D'>MHRA-UK Guidelines</span></a><br> <br /> <br style='mso-special-character:line-break'> <br /> <![if !supportLineBreakNewLine]><br style='mso-special-character:line-break'> <br /> <![endif]><o:p></o:p></span></p> <br /> <p class=MsoNormal style='margin-bottom:12.0pt;line-height:15.6pt'><span class=GramE><span style='font-size:9.0pt;font-family:Symbol;mso-ascii-font-family: Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>·</span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><span style='mso-spacerun:yes'> </span></span></span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><a href="http://pharmaguideline.blogspot.com/2010/10/mcc.html"><span style='mso-bidi-font-size:12.0pt;color:#307F0D'>MCC Guidelines -South Africa</span></a><br> <br /> <br style='mso-special-character:line-break'> <br /> <![if !supportLineBreakNewLine]><br style='mso-special-character:line-break'> <br /> <![endif]><o:p></o:p></span></p> <br /> <p class=MsoNormal style='margin-bottom:12.0pt;line-height:15.6pt'><span class=GramE><span style='font-size:9.0pt;font-family:Symbol;mso-ascii-font-family: Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>·</span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><span style='mso-spacerun:yes'> </span></span></span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><a href="http://pharmaguideline.blogspot.com/2010/10/tga.html"><span style='mso-bidi-font-size:12.0pt;color:#307F0D'>TGA Guidelines-Australia</span></a><br> <br /> <br style='mso-special-character:line-break'> <br /> <![if !supportLineBreakNewLine]><br style='mso-special-character:line-break'> <br /> <![endif]><o:p></o:p></span></p> <br /> <p class=MsoNormal style='margin-bottom:12.0pt;line-height:15.6pt'><span class=GramE><span style='font-size:9.0pt;font-family:Symbol;mso-ascii-font-family: Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>·</span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><span style='mso-spacerun:yes'> </span></span></span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><a href="http://www.mcaz.co.zw/trials/MCAZ%20Amendment%20guidelines.pdf" target="_blank"><span style='mso-bidi-font-size:12.0pt;color:#307F0D'>MCA<br /> Guidelines-Zimbabwe</span></a><br> <br /> <br style='mso-special-character:line-break'> <br /> <![if !supportLineBreakNewLine]><br style='mso-special-character:line-break'> <br /> <![endif]><o:p></o:p></span></p> <br /> <p class=MsoNormal style='margin-bottom:12.0pt;line-height:15.6pt'><span class=GramE><span style='font-size:9.0pt;font-family:Symbol;mso-ascii-font-family: Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'>·</span><span style='font-size:9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'><span style='mso-spacerun:yes'> </span></span></span><span style='font-size:9.0pt;mso-bidi-font-size:12.0pt;font-family:Verdana; mso-bidi-font-family:"Times New Roman";color:#307F0D'><a href="http://pharmaguideline.blogspot.com/2010/10/schedule-m.html"><span style='color:#307F0D'>Schedule M-India</span></a></span><span style='font-size: 9.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman";color:#333333'><br> <br /> <br style='mso-special-character:line-break'> <br /> <![if !supportLineBreakNewLine]><br style='mso-special-character:line-break'> <br /> <![endif]><o:p></o:p></span></p> <br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-size:10.0pt; font-family:inherit;mso-bidi-font-family:"Times New Roman";color:#333333'><a href="http://pharmaguideline.blogspot.com/2010/12/validation.html" target="_blank"><b><span style='mso-bidi-font-size:12.0pt;color:#307F0D'>Validation</span></b></a></span><span style='font-size:9.0pt;font-family:inherit;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-size:10.0pt; font-family:inherit;mso-bidi-font-family:"Times New Roman";color:#333333'><a href="http://pharmaguideline.blogspot.com/2010/12/non-sterile-process-validation.html" target="_blank"><b><span style='mso-bidi-font-size:12.0pt;color:#307F0D'>Non-sterile<br /> process validation</span></b></a></span><span style='font-size:9.0pt; font-family:inherit;mso-bidi-font-family:"Times New Roman";color:#333333'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-size:10.0pt; font-family:inherit;mso-bidi-font-family:"Times New Roman";color:#333333'><a href="http://pharmaguideline.blogspot.com/2010/12/cleaning-validation.html" target="_blank"><b><span style='mso-bidi-font-size:12.0pt;color:#307F0D'>Cleaning<br /> Validation</span></b></a><b> </b></span><span style='font-size:9.0pt; font-family:inherit;mso-bidi-font-family:"Times New Roman";color:#333333'><o:p></o:p></span></p> <br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-size:10.0pt; font-family:inherit;mso-bidi-font-family:"Times New Roman";color:#333333'><a href="http://pharmaguideline.blogspot.com/2010/12/qualification-of-systems-and-equipment.html" target="_blank"><b><span style='mso-bidi-font-size:12.0pt;color:#307F0D'>Qualification<br /> of systems and equipment</span></b></a></span><span style='font-size:9.0pt; font-family:inherit;mso-bidi-font-family:"Times New Roman";color:#333333'><o:p></o:p></span></p> <br /> <p class=MsoNormal><o:p> </o:p></p> <br /> </div> <br /> </body> <br /> <br /> </html>http://scholarpharma.blogspot.com/2012/01/who-guidelines.html0margipatel02@gmail.com (margipatel02@gmail.com)noWHO Guidelines RAJA RAJA 1 1 2012-01-02T04:20:00Z 2012-01-02T04:21:00Z 1 779 4441 <egyptian hak> 37 10 5210 11.6568 Clean Clean false false false MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman"; mso-ansi-language:#0400; mso-fareast-language:#0400; mso-bidi-language:#0400;} WHO Guidelines World health organization (WHO) provide the GMP guidelines for pharmaceuticals. These guidelines are followed through the world. These guidelines cover all the pharmaceutical topics as: 1. Process validation 2. Cleaning validation 3. Analytical method validation 4. DQ, IQ, OQ, PQ of equipments 5. Water system validation 6. HVAC validation 7. Computer system validation 8. Market complaint handling 9. Product recalls 10 Stability studies and may more... Following are the general guidelines of WHO. · General · Volume 2, 2nd updated edition WHO guidelines for Active Pharmaceutical Ingredients · API   New TRS WHO Technical Report Series 961, 2011 44th report English WHO Technical Report Series 957, 2010 43rd report English pdf, 999kb WHO Technical Report Series 953, 2009 42nd report English pdf, 593kb WHO Technical Report Series 948, 2008 41st report English pdf, 1.22Mb WHO Technical Report Series 943, 2007 40th report WHO Technical Report Series 937, 2006 English [pdf 2.08Mb] 39th report WHO Technical Report Series 929, 2005 English [1.21Mb] 38th report WHO Technical Report Series 917, 2003 English [pdf 386kb] 37th report WHO Technical Report Series 908, 2003 English [pdf 632kb] 36th report WHO Technical Report Series 902, 2002 English [pdf 1Mb] 35th report WHO Technical Report Series 885, 1999 English [pdf 7Mb] 34th report WHO Technical Report Series 863, 1996 English Part 1 [pdf 3.8Mb]  English Part 2 [pdf 4Mb] 33rd report WHO Technical Report Series 834, 1993 English [pdf 1.5Mb] 32nd report WHO Technical Report Series 823, 1992 English [pdf 6.4Mb]    · Risk analysis · Training materials · An introduction, resource and study pack for trainers · Blood and Biological Products · Radio Pharmaceuticals · Further References Also Read: · ISO Guidelines · US-FDA Guidelines · ICH Guidelines · MHRA-UK Guidelines · MCC Guidelines -South Africa · TGA Guidelines-Australia · MCA Guidelines-Zimbabwe · Schedule M-India Validation Non-sterile process validation Cleaning Validation  Qualification of systems and equipment  margipatel02@gmail.comWHO Guidelines RAJA RAJA 1 1 2012-01-02T04:20:00Z 2012-01-02T04:21:00Z 1 779 4441 <egyptian hak> 37 10 5210 11.6568 Clean Clean false false false MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:10.0pt; font-family:"Times New Roman"; mso-ansi-language:#0400; mso-fareast-language:#0400; mso-bidi-language:#0400;} WHO Guidelines World health organization (WHO) provide the GMP guidelines for pharmaceuticals. These guidelines are followed through the world. These guidelines cover all the pharmaceutical topics as: 1. Process validation 2. Cleaning validation 3. Analytical method validation 4. DQ, IQ, OQ, PQ of equipments 5. Water system validation 6. HVAC validation 7. Computer system validation 8. Market complaint handling 9. Product recalls 10 Stability studies and may more... Following are the general guidelines of WHO. · General · Volume 2, 2nd updated edition WHO guidelines for Active Pharmaceutical Ingredients · API   New TRS WHO Technical Report Series 961, 2011 44th report English WHO Technical Report Series 957, 2010 43rd report English pdf, 999kb WHO Technical Report Series 953, 2009 42nd report English pdf, 593kb WHO Technical Report Series 948, 2008 41st report English pdf, 1.22Mb WHO Technical Report Series 943, 2007 40th report WHO Technical Report Series 937, 2006 English [pdf 2.08Mb] 39th report WHO Technical Report Series 929, 2005 English [1.21Mb] 38th report WHO Technical Report Series 917, 2003 English [pdf 386kb] 37th report WHO Technical Report Series 908, 2003 English [pdf 632kb] 36th report WHO Technical Report Series 902, 2002 English [pdf 1Mb] 35th report WHO Technical Report Series 885, 1999 English [pdf 7Mb] 34th report WHO Technical Report Series 863, 1996 English Part 1 [pdf 3.8Mb]  English Part 2 [pdf 4Mb] 33rd report WHO Technical Report Series 834, 1993 English [pdf 1.5Mb] 32nd report WHO Technical Report Series 823, 1992 English [pdf 6.4Mb]    · Risk analysis · Training materials · An introduction, resource and study pack for trainers · Blood and Biological Products · Radio Pharmaceuticals · Further References Also Read: · ISO Guidelines · US-FDA Guidelines · ICH Guidelines · MHRA-UK Guidelines · MCC Guidelines -South Africa · TGA Guidelines-Australia · MCA Guidelines-Zimbabwe · Schedule M-India Validation Non-sterile process validation Cleaning Validation  Qualification of systems and equipment  USFDA,guidelines,GMP,guidelines,WHO,guidelines,Schedule,M,FDA,European,guidelines,cleaning,validation,process,validation,water,system,validation,ICH,guidelines,GMP,audut,compliance,equipment,qualification,Installation,Qualification,Operationaltag:blogger.com,1999:blog-8563020669307343167.post-6102889252264788396Mon, 02 Jan 2012 04:16:00 +00002012-01-01T20:18:39.899-08:00Procedure for change control in pharmaceuticalsProcedure for change control in pharmaceuticals<html xmlns:o="urn:schemas-microsoft-com:office:office" xmlns:w="urn:schemas-microsoft-com:office:word" xmlns="http://www.w3.org/TR/REC-html40"><br /> <br /> <head><br /> <meta http-equiv=Content-Type content="text/html; charset=windows-1252"><br /> <meta name=ProgId content=Word.Document><br /> <meta name=Generator content="Microsoft Word 11"><br /> <meta name=Originator content="Microsoft Word 11"><br /> <link rel=File-List href="Procedure%20for%20change%20control%20in%20pharmaceuticals%20)_files/filelist.xml"><br /> <title>Procedure for change control in pharmaceuticals</title><br /> <br /> <style>  </style><br /> <br /> </head><br /> <br /> <body lang=EN-US style='tab-interval:.5in'><br /> <br /> <div class=Section1><br /> <p class=MsoNormal style='line-height:13.2pt;mso-outline-level:3'><b><span style='font-size:11.0pt;font-family:Verdana;mso-bidi-font-family:"Times New Roman"; color:#333333'>Procedure for change control in pharmaceuticals<o:p></o:p></span></b></p><br /> <p class=MsoNormal style='margin-left:45.0pt;text-indent:-45.0pt;line-height: 12.9pt'><b><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"; color:#333333'>1.0</span></b><span style='font-family:inherit;mso-bidi-font-family: "Times New Roman";color:#333333'>         <b>Purpose:</b></span><span style='font-size:9.0pt;font-family:inherit;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p></o:p></span></p><br /> <p class=MsoNormal style='line-height:15.6pt'><span class=GramE><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman";color:#333333'>To<br /> describe a procedure for change control.</span></span><span style='font-size: 9.0pt;font-family:inherit;mso-bidi-font-family:"Times New Roman";color:#333333'><o:p></o:p></span></p><br /> <p class=MsoNormal style='margin-left:44.55pt;text-indent:-44.55pt;line-height: 12.9pt'><b><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"; color:#333333'>2.0</span></b><span style='font-family:inherit;mso-bidi-font-family: "Times New Roman";color:#333333'>         <b>Scope:</b></span><span style='font-size:9.0pt;font-family:inherit;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p></o:p></span></p><br /> <p class=MsoNormal style='text-align:justify;line-height:12.9pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman";color:#333333'>This<br /> SOP shall be applicable for the identification, documentation, appropriate<br /> review and approval of changes in raw materials, specifications, analytical<br /> methods, facilities, support systems, equipment (including computer hardware)<br /> processing steps, labeling and packaging materials, and computer software.</span><span style='font-size:9.0pt;font-family:inherit;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p></o:p></span></p><br /> <p class=MsoNormal style='margin-left:.25in;text-indent:-.25in;line-height: 12.9pt'><b><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"; color:#333333'>3.0</span></b><span style='font-family:inherit;mso-bidi-font-family: "Times New Roman";color:#333333'>         <b>Responsibility:</b></span><span style='font-size:9.0pt;font-family:inherit;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p></o:p></span></p><br /> <p class=MsoNormal style='text-align:justify;text-indent:9.0pt;line-height: 12.9pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"; color:black'>Designee of Originating<br /> Department:         </span><span style='font-size:9.0pt;font-family:inherit;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p></o:p></span></p><br /> <p class=MsoNormal style='margin-left:4.5pt;text-indent:-4.5pt;line-height: 12.9pt'><b><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"; color:#333333'>4.0         Procedure:</span></b><span style='font-size:9.0pt;font-family:inherit;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p></o:p></span></p><br /> <p class=MsoNormal style='margin-left:24.0pt;text-align:justify;text-indent: -24.0pt;line-height:12.9pt'><span style='font-family:inherit;mso-bidi-font-family: "Times New Roman";color:#333333'>1.          The<br /> initiating department shall initiate the change as per the change control<br /> format no.</span><span style='font-size:9.0pt;font-family:inherit;mso-bidi-font-family: "Times New Roman";color:#333333'><o:p></o:p></span></p><br /> <p class=MsoNormal style='margin-left:24.0pt;text-align:justify;text-indent: -24.0pt;line-height:12.9pt'><span style='font-family:inherit;mso-bidi-font-family: "Times New Roman";color:#333333'>2.          The<br /> initiating department shall furnish the details very clearly in the form for<br /> present process/use, proposed change, Justification & impact analysis and<br /> acceptance criteria.</span><span style='font-size:9.0pt;font-family:inherit; mso-bidi-font-family:"Times New Roman";color:#333333'><o:p></o:p></span></p><br /> <p class=MsoNormal style='margin-left:24.0pt;text-align:justify;text-indent: -24.0pt;line-height:12.9pt'><span style='font-family:inherit;mso-bidi-font-family: "Times New Roman";color:#333333'>3.          The<br /> initiating department shall also define changes as major or minor based on<br /> product quality or its impact of safety, health and environmental aspects. Some<br /> of the major and minor changes are listed below: -</span><span style='font-size:9.0pt;font-family:inherit;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p></o:p></span></p><br /> <p class=MsoNormal style='text-align:justify;line-height:12.9pt'><b><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman";color:#333333'>3.1       <br /> Major Changes</span></b><span style='font-size:9.0pt;font-family:inherit; mso-bidi-font-family:"Times New Roman";color:#333333'><o:p></o:p></span></p><br /> <p class=MsoNormal style='margin-left:30.0pt;text-align:justify;text-indent: -30.0pt;line-height:12.9pt'><span class=GramE><u><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman";color:#333333'>For a substance of<br /> chemical and microbiological quality evaluation</span></u><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman";color:#333333'>.</span></span><span style='font-size:9.0pt;font-family:inherit;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p></o:p></span></p><br /> <p class=MsoNormal style='margin-left:30.0pt;text-indent:-30.0pt;line-height: 15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"; color:#333333'>•         Addition or<br /> deletion of a step or addition of an alternative/new step in the formulation<br /> manufacturing process.</span><span style='font-size:9.0pt;font-family:inherit; mso-bidi-font-family:"Times New Roman";color:#333333'><o:p></o:p></span></p><br /> <p class=MsoNormal style='margin-left:30.0pt;text-indent:-30.0pt;line-height: 15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"; color:#333333'>•         Addition of a new<br /> manufacturing site with modification of the formulation manufacturing process<br /> described in the original dossier/document.</span><span style='font-size:9.0pt; font-family:inherit;mso-bidi-font-family:"Times New Roman";color:#333333'><o:p></o:p></span></p><br /> <p class=MsoNormal style='margin-left:30.0pt;text-indent:-30.0pt;line-height: 15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"; color:#333333'>•         Change in input<br /> quantities of formulation manufacturing process.</span><span style='font-size: 9.0pt;font-family:inherit;mso-bidi-font-family:"Times New Roman";color:#333333'><o:p></o:p></span></p><br /> <p class=MsoNormal style='margin-left:30.0pt;text-indent:-30.0pt;line-height: 15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"; color:#333333'>•         Changes in the<br /> quality of raw material(s) or key intermediate(s) used in the formulation<br /> manufacturing process.</span><span style='font-size:9.0pt;font-family:inherit; mso-bidi-font-family:"Times New Roman";color:#333333'><o:p></o:p></span></p><br /> <p class=MsoNormal style='margin-left:30.0pt;text-indent:-30.0pt;line-height: 15.6pt'><span style='font-size:9.0pt;font-family:inherit;mso-bidi-font-family: "Times New Roman";color:#333333'><o:p> </o:p></span></p><br /> <p class=MsoNormal style='text-align:justify;line-height:12.9pt'><b><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman";color:#333333'>3.2.   <br /> Minor Changes</span></b><span style='font-size:9.0pt;font-family:inherit; mso-bidi-font-family:"Times New Roman";color:#333333'><o:p></o:p></span></p><br /> <p class=MsoNormal style='margin-left:30.0pt;text-align:justify;text-indent: -30.0pt;line-height:12.9pt'><span style='font-family:inherit;mso-bidi-font-family: "Times New Roman";color:#333333'>•        <br /> Change in the administrative references (name/company name, address) of the<br /> certificate holder.</span><span style='font-size:9.0pt;font-family:inherit; mso-bidi-font-family:"Times New Roman";color:#333333'><o:p></o:p></span></p><br /> <p class=MsoNormal style='margin-left:30.0pt;text-indent:-30.0pt;line-height: 15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"; color:#333333'>•         Change in the<br /> references (name/company name, address) of the manufacturing site.</span><span style='font-size:9.0pt;font-family:inherit;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p></o:p></span></p><br /> <p class=MsoNormal style='margin-left:30.0pt;text-indent:-30.0pt;line-height: 15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"; color:#333333'>•         Change or updating<br /> of the methods of analysis used to test the substance.</span><span style='font-size:9.0pt;font-family:inherit;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p></o:p></span></p><br /> <p class=MsoNormal style='margin-left:30.0pt;text-indent:-30.0pt;line-height: 15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"; color:#333333'>•         Change in the<br /> specifications of the substance.</span><span style='font-size:9.0pt;font-family: inherit;mso-bidi-font-family:"Times New Roman";color:#333333'><o:p></o:p></span></p><br /> <p class=MsoNormal style='margin-left:30.0pt;text-indent:-30.0pt;line-height: 15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"; color:#333333'>•         Change in supplier<br /> of starting and packing material.</span><span style='font-size:9.0pt; font-family:inherit;mso-bidi-font-family:"Times New Roman";color:#333333'><o:p></o:p></span></p><br /> <p class=MsoNormal style='margin-left:30.0pt;text-indent:-30.0pt;line-height: 15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"; color:#333333'>•         Change in the batch<br /> size.</span><span style='font-size:9.0pt;font-family:inherit;mso-bidi-font-family: "Times New Roman";color:#333333'><o:p></o:p></span></p><br /> <p class=MsoNormal style='margin-left:30.0pt;text-indent:-30.0pt;line-height: 15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"; color:#333333'>•         Addition of a<br /> new manufacturing site in the same site as described in the original dossier.</span><span style='font-size:9.0pt;font-family:inherit;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p></o:p></span></p><br /> <p class=MsoNormal style='margin-left:30.0pt;text-indent:-30.0pt;line-height: 15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"; color:#333333'>•         Change in the<br /> documents like SOPs etc.</span><span style='font-size:9.0pt;font-family:inherit; mso-bidi-font-family:"Times New Roman";color:#333333'><o:p></o:p></span></p><br /> <p class=MsoNormal style='margin-left:24.0pt;text-align:justify;text-indent: -24.0pt;line-height:12.9pt'><span style='font-family:inherit;mso-bidi-font-family: "Times New Roman";color:#333333'>4.          The<br /> Initiating department shall forward the proposal as per the requirement<br /> to Formulation & Development Department for comments and clearance.</span><span style='font-size:9.0pt;font-family:inherit;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p></o:p></span></p><br /> <p class=MsoNormal style='margin-left:24.0pt;text-align:justify;text-indent: -24.0pt;line-height:12.9pt'><span style='font-family:inherit;mso-bidi-font-family: "Times New Roman";color:#333333'>5.          After<br /> giving comments/clearance, Formulation & Development shall forward the<br /> change control form to Quality assurance department.</span><span style='font-size:9.0pt;font-family:inherit;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p></o:p></span></p><br /> <p class=MsoNormal style='margin-left:24.0pt;text-align:justify;text-indent: -24.0pt;line-height:12.9pt'><span style='font-family:inherit;mso-bidi-font-family: "Times New Roman";color:#333333'>6.          On<br /> receipt of Change control form from F & D department, QA shall assign the<br /> Change control number as per the procedure given below:</span><span style='font-size:9.0pt;font-family:inherit;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p></o:p></span></p><br /> <p class=MsoNormal style='text-align:justify;line-height:12.9pt'><i><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman";color:#333333'>                      <u>Assigning<br /> a change control number</u></span></i><span style='font-size:9.0pt;font-family: inherit;mso-bidi-font-family:"Times New Roman";color:#333333'><o:p></o:p></span></p><br /> <p class=MsoNormal style='margin-left:.25in;text-align:justify;text-indent: -.25in;line-height:12.9pt'><i><span style='font-family:inherit;mso-bidi-font-family: "Times New Roman";color:#333333'>      Each change<br /> control number contains seven digits.</span></i><span style='font-size:9.0pt; font-family:inherit;mso-bidi-font-family:"Times New Roman";color:#333333'><o:p></o:p></span></p><br /> <p class=MsoNormal style='margin-left:.25in;text-align:justify;text-indent: -.25in;line-height:12.9pt'><i><span style='font-family:inherit;mso-bidi-font-family: "Times New Roman";color:#333333'>-     First two digits<br /> represents change control code.</span></i><span style='font-size:9.0pt; font-family:inherit;mso-bidi-font-family:"Times New Roman";color:#333333'><o:p></o:p></span></p><br /> <p class=MsoNormal style='margin-left:.25in;text-align:justify;text-indent: -.25in;line-height:12.9pt'><i><span style='font-family:inherit;mso-bidi-font-family: "Times New Roman";color:#333333'>-     Third, forth and<br /> fifth digit represent sequential change control No. (001 to 999)</span></i><span style='font-size:9.0pt;font-family:inherit;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p></o:p></span></p><br /> <p class=MsoNormal style='margin-left:.25in;text-align:justify;text-indent: -.25in;line-height:12.9pt'><i><span style='font-family:inherit;mso-bidi-font-family: "Times New Roman";color:#333333'>-     Sixth and seventh<br /> digit represents last two digits of the current year. <span class=GramE>(e.g.01,<br /> 02, 03…...99).</span></span></i><span style='font-size:9.0pt;font-family:inherit; mso-bidi-font-family:"Times New Roman";color:#333333'><o:p></o:p></span></p><br /> <p class=MsoNormal style='text-align:justify;line-height:12.9pt'><i><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman";color:#333333'>For<br /> example, following change control no is decoded as explained.</span></i><span style='font-size:9.0pt;font-family:inherit;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p></o:p></span></p><br /> <p class=MsoNormal style='text-align:justify;line-height:12.9pt'><i><span lang=FR style='font-family:inherit;mso-bidi-font-family:"Times New Roman"; color:#333333;mso-ansi-language:FR'>CC-001/ 03.</span></i><span style='font-size:9.0pt;font-family:inherit;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p></o:p></span></p><br /> <p class=MsoNormal style='text-align:justify;line-height:12.9pt'><i><span lang=FR style='font-family:inherit;mso-bidi-font-family:"Times New Roman"; color:#333333;mso-ansi-language:FR'>CC = Change control code.</span></i><span style='font-size:9.0pt;font-family:inherit;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p></o:p></span></p><br /> <p class=MsoNormal style='text-align:justify;line-height:12.9pt'><i><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman";color:#333333'>001=<br /> Sequential Change control Number (001, 002, 003…………..999). </span></i><span style='font-size:9.0pt;font-family:inherit;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p></o:p></span></p><br /> <p class=MsoNormal style='text-align:justify;line-height:12.9pt'><i><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman";color:#333333'>03=<br /> Current year 20<b>03 </b>(Last two digit of current year)</span></i><span style='font-size:9.0pt;font-family:inherit;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p></o:p></span></p><br /> <p class=MsoNormal style='text-align:justify;line-height:12.9pt'><span style='font-size:9.0pt;font-family:inherit;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p> </o:p></span></p><br /> <p class=MsoNormal style='margin-left:24.0pt;text-align:justify;text-indent: -24.0pt;line-height:12.9pt'><span style='font-family:inherit;mso-bidi-font-family: "Times New Roman";color:#333333'>7.          QA<br /> shall enter the details of Change in the Change control register.</span><span style='font-size:9.0pt;font-family:inherit;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p></o:p></span></p><br /> <p class=MsoNormal style='margin-left:24.0pt;text-align:justify;text-indent: -24.0pt;line-height:12.9pt'><span style='font-family:inherit;mso-bidi-font-family: "Times New Roman";color:#333333'>8.          QA<br /> shall evaluate the feasibility of the change and forward the change control<br /> form to Regulatory affairs, if required.</span><span style='font-size:9.0pt; font-family:inherit;mso-bidi-font-family:"Times New Roman";color:#333333'><o:p></o:p></span></p><br /> <p class=MsoNormal style='margin-left:24.0pt;text-align:justify;text-indent: -24.0pt;line-height:12.9pt'><span style='font-family:inherit;mso-bidi-font-family: "Times New Roman";color:#333333'>9.          Regulatory<br /> affairs shall evaluate the change in terms of any need to inform customer or<br /> any <span class=SpellE>updation</span> in dossiers etc. and forward the change<br /> to Site Quality Head.</span><span style='font-size:9.0pt;font-family:inherit; mso-bidi-font-family:"Times New Roman";color:#333333'><o:p></o:p></span></p><br /> <p class=MsoNormal style='margin-left:24.0pt;text-align:justify;text-indent: -24.0pt;line-height:12.9pt'><span style='font-family:inherit;mso-bidi-font-family: "Times New Roman";color:#333333'>10.      Site<br /> Quality Head shall receive the comment form all the concerns and takes the<br /> decision of approving or rejecting the change.</span><span style='font-size: 9.0pt;font-family:inherit;mso-bidi-font-family:"Times New Roman";color:#333333'><o:p></o:p></span></p><br /> <p class=MsoNormal style='margin-left:24.0pt;text-align:justify;text-indent: -24.0pt;line-height:12.9pt'><span style='font-family:inherit;mso-bidi-font-family: "Times New Roman";color:#333333'>11.      On<br /> completion of the total procedure, QA shall formally enter the status in Change<br /> control Register and close the Change control Procedure.</span><span style='font-size:9.0pt;font-family:inherit;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p></o:p></span></p><br /> <p class=MsoNormal style='margin-left:24.0pt;text-align:justify;text-indent: -24.0pt;line-height:12.9pt'><span style='font-family:inherit;mso-bidi-font-family: "Times New Roman";color:#333333'>12.      Put the<br /> stamp of ‘OBSOLATE COPY’ on the old documents, where every this change control<br /> procedure is applicable.</span><span style='font-size:9.0pt;font-family: inherit;mso-bidi-font-family:"Times New Roman";color:#333333'><o:p></o:p></span></p><br /> <p class=MsoNormal style='text-align:justify;line-height:12.9pt'><span style='font-size:9.0pt;font-family:inherit;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p> </o:p></span></p><br /> <p class=MsoNormal style='line-height:12.9pt'><b><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman";color:#333333'>5.0      <br /> <br /> Revision Log:</span></b><span style='font-size:9.0pt;font-family:inherit; mso-bidi-font-family:"Times New Roman";color:#333333'><o:p></o:p></span></p><br /> <p class=MsoNormal style='line-height:12.9pt'><span style='font-size:9.0pt; font-family:inherit;mso-bidi-font-family:"Times New Roman";color:#333333'><o:p> </o:p></span></p><br /> <table class=MsoNormalTable border=0 cellspacing=0 cellpadding=0 style='margin-left:23.4pt;border-collapse:collapse;mso-padding-alt:0in 0in 0in 0in'><tr style='mso-yfti-irow:0;mso-yfti-firstrow:yes'> <td width=196 valign=top style='width:147.0pt;border:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:12.25pt'><b><span style='mso-bidi-font-family:"Times New Roman"'>Revision No.</span></b><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p></td> <td width=196 valign=top style='width:147.0pt;border:solid windowtext 1.0pt; border-left:none;padding:0in 5.4pt 0in 5.4pt'><br /> <br /> <p class=MsoNormal align=center style='text-align:center;line-height:12.25pt'><b><span style='mso-bidi-font-family:"Times New Roman"'>Effective Date</span></b><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p></td> <td width=196 valign=top style='width:147.0pt;border:solid windowtext 1.0pt; border-left:none;padding:0in 5.4pt 0in 5.4pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:12.25pt'><b><span style='mso-bidi-font-family:"Times New Roman"'>Reason</span></b><span style='mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p></td> </tr> <tr style='mso-yfti-irow:1;mso-yfti-lastrow:yes'> <td width=196 valign=top style='width:147.0pt;border:solid windowtext 1.0pt; border-top:none;padding:0in 5.4pt 0in 5.4pt'><br /> <br /> <p class=MsoNormal align=center style='text-align:center;line-height:12.25pt'><span style='mso-bidi-font-family:"Times New Roman"'>01<o:p></o:p></span></p></td> <td width=196 valign=top style='width:147.0pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:12.25pt'><span style='mso-bidi-font-family:"Times New Roman"'>15.04.05<o:p></o:p></span></p></td> <td width=196 valign=top style='width:147.0pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:12.25pt'><span style='mso-bidi-font-family:"Times New Roman"'>Format Changed<o:p></o:p></span></p><br /> </td> </tr> </table><br /> <p class=MsoNormal style='line-height:12.9pt'><b><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman";color:#333333'>  <br />         </span></b><span style='font-size:9.0pt;font-family:inherit;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p></o:p></span></p><br /> <p class=MsoNormal style='margin-left:45.0pt;text-indent:-45.0pt;line-height: 12.9pt'><b><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"; color:#333333'>6.0</span></b><span style='font-family:inherit;mso-bidi-font-family: "Times New Roman";color:#333333'>                    <b>Abbreviations:</b></span><span style='font-size:9.0pt;font-family:inherit;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p></o:p></span></p><br /> <table class=MsoNormalTable border=0 cellspacing=0 cellpadding=0 width=528 style='width:5.5in;margin-left:36.45pt;border-collapse:collapse;mso-padding-alt: 0in 0in 0in 0in'><tr style='mso-yfti-irow:0;mso-yfti-firstrow:yes;height:20.25pt'> <td width=127 valign=top style='width:94.95pt;border:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:20.25pt'><br /> <br /> <p class=MsoNormal style='line-height:12.9pt'><b><span style='mso-bidi-font-family: "Times New Roman"'>Abbreviation</span></b><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p></td> <td width=456 valign=top style='width:4.75in;border:solid windowtext 1.0pt; border-left:none;padding:0in 5.4pt 0in 5.4pt;height:20.25pt'><br /> <p class=MsoNormal style='line-height:15.6pt'><b><span style='mso-bidi-font-family: "Times New Roman"'>Expanded Form</span></b><span style='mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p></td> </tr> <tr style='mso-yfti-irow:1;height:20.25pt'> <td width=127 valign=top style='width:94.95pt;border:solid windowtext 1.0pt; border-top:none;padding:0in 5.4pt 0in 5.4pt;height:20.25pt'><br /> <br /> <p class=MsoNormal style='line-height:12.9pt'><span style='mso-bidi-font-family: "Times New Roman"'><o:p> </o:p></span></p><p class=MsoNormal style='line-height:15.6pt'><span style='mso-bidi-font-family: "Times New Roman"'>QA<o:p></o:p></span></p></td> <td width=456 valign=top style='width:4.75in;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:20.25pt'><br /> <p class=MsoNormal style='line-height:12.9pt'><span style='mso-bidi-font-family: "Times New Roman"'><o:p> </o:p></span></p><p class=MsoNormal style='line-height:15.6pt'><span style='mso-bidi-font-family: "Times New Roman"'>Quality Assurance<o:p></o:p></span></p></td> </tr> <tr style='mso-yfti-irow:2;height:20.25pt'> <td width=127 valign=top style='width:94.95pt;border:solid windowtext 1.0pt; border-top:none;padding:0in 5.4pt 0in 5.4pt;height:20.25pt'><br /> <p class=MsoNormal style='line-height:12.9pt'><span style='mso-bidi-font-family: "Times New Roman"'><o:p> </o:p></span></p><p class=MsoNormal style='line-height:15.6pt'><span style='mso-bidi-font-family: "Times New Roman"'>VP<o:p></o:p></span></p></td> <td width=456 valign=top style='width:4.75in;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:20.25pt'><br /> <p class=MsoNormal style='line-height:12.9pt'><span style='mso-bidi-font-family: "Times New Roman"'><o:p> </o:p></span></p><p class=MsoNormal style='line-height:15.6pt'><span style='mso-bidi-font-family: "Times New Roman"'>Vice President<o:p></o:p></span></p><br /> </td> </tr> <tr style='mso-yfti-irow:3;height:21.25pt'> <td width=127 valign=top style='width:94.95pt;border:solid windowtext 1.0pt; border-top:none;padding:0in 5.4pt 0in 5.4pt;height:21.25pt'><br /> <p class=MsoNormal style='line-height:12.9pt'><span style='mso-bidi-font-family: "Times New Roman"'><o:p> </o:p></span></p><p class=MsoNormal style='line-height:15.6pt'><span style='mso-bidi-font-family: "Times New Roman"'>SOP<o:p></o:p></span></p></td> <td width=456 valign=top style='width:4.75in;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:21.25pt'><br /> <br /> <p class=MsoNormal style='line-height:12.9pt'><span style='mso-bidi-font-family: "Times New Roman"'><o:p> </o:p></span></p><p class=MsoNormal style='line-height:15.6pt'><span style='mso-bidi-font-family: "Times New Roman"'>Standard Operating Procedure<o:p></o:p></span></p></td> </tr> <tr style='mso-yfti-irow:4;height:20.25pt'> <td width=127 valign=top style='width:94.95pt;border:solid windowtext 1.0pt; border-top:none;padding:0in 5.4pt 0in 5.4pt;height:20.25pt'><br /> <p class=MsoNormal style='line-height:12.9pt'><span style='mso-bidi-font-family: "Times New Roman"'><o:p> </o:p></span></p><p class=MsoNormal style='line-height:15.6pt'><span style='mso-bidi-font-family: "Times New Roman"'>F & D<o:p></o:p></span></p><br /> </td> <td width=456 valign=top style='width:4.75in;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:20.25pt'><br /> <p class=MsoNormal style='line-height:12.9pt'><span style='mso-bidi-font-family: "Times New Roman"'><o:p> </o:p></span></p><p class=MsoNormal style='line-height:15.6pt'><span style='mso-bidi-font-family: "Times New Roman"'>Formulation & Development<o:p></o:p></span></p></td> </tr> <tr style='mso-yfti-irow:5;mso-yfti-lastrow:yes;height:20.25pt'> <td width=127 valign=top style='width:94.95pt;border:solid windowtext 1.0pt; border-top:none;padding:0in 5.4pt 0in 5.4pt;height:20.25pt'><br /> <p class=MsoNormal style='line-height:15.6pt'><span style='mso-bidi-font-family: "Times New Roman"'><o:p> </o:p></span></p></td> <td width=456 valign=top style='width:4.75in;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:20.25pt'><br /> <p class=MsoNormal style='line-height:15.6pt'><span style='mso-bidi-font-family: "Times New Roman"'><o:p> </o:p></span></p></td> </tr> </table><br /> <p class=MsoNormal style='line-height:12.9pt'><b><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman";color:#333333'>7.0         <br /> <br /> Annexure:</span></b><span style='font-size:9.0pt;font-family:inherit; mso-bidi-font-family:"Times New Roman";color:#333333'><o:p></o:p></span></p><br /> <p class=MsoNormal style='line-height:12.9pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman";color:#333333'>              <br /> Annexure-1:      Change Control Form</span><span style='font-size:9.0pt;font-family:inherit;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p></o:p></span></p><br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-size:9.0pt; font-family:inherit;mso-bidi-font-family:"Times New Roman";color:#333333'><o:p> </o:p></span></p><br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-size:9.0pt; font-family:inherit;mso-bidi-font-family:"Times New Roman";color:#333333'><o:p> </o:p></span></p><br /> <p class=MsoNormal style='line-height:12.9pt'><b><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman";color:#333333'>       <br />                                                               Annexure-1</span></b><span style='font-size:9.0pt;font-family:inherit;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p></o:p></span></p><br /> <p class=MsoNormal style='line-height:12.9pt'><b><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman";color:#333333'>                                                              <br /> Change Control Form</span></b><span style='font-size:9.0pt;font-family:inherit; mso-bidi-font-family:"Times New Roman";color:#333333'><o:p></o:p></span></p><br /> <table class=MsoNormalTable border=0 cellspacing=0 cellpadding=0 width=576 style='width:6.0in;margin-left:.2in;border-collapse:collapse;mso-padding-alt: 0in 0in 0in 0in'><tr style='mso-yfti-irow:0;mso-yfti-firstrow:yes;height:14.8pt'> <td width=30 rowspan=5 valign=top style='width:22.5pt;border:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:14.8pt'><br /> <p class=MsoNormal style='line-height:12.9pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'>1.<o:p></o:p></span></p></td> <td width=168 valign=top style='width:1.75in;border:solid windowtext 1.0pt; border-left:none;padding:0in 5.4pt 0in 5.4pt;height:14.8pt'><br /> <p class=MsoNormal style='line-height:12.9pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'>Initiating Dept<o:p></o:p></span></p><br /> </td> <td width=288 colspan=2 valign=top style='width:3.0in;border:solid windowtext 1.0pt; border-left:none;padding:0in 5.4pt 0in 5.4pt;height:14.8pt'><br /> <p class=MsoNormal style='line-height:12.9pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width=150 valign=top style='width:112.5pt;border:solid windowtext 1.0pt; border-left:none;padding:0in 5.4pt 0in 5.4pt;height:14.8pt'><br /> <p class=MsoNormal style='line-height:12.9pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> </tr> <tr style='mso-yfti-irow:1;height:16.6pt'> <td width=168 valign=top style='width:1.75in;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:16.6pt'><br /> <p class=MsoNormal style='line-height:12.9pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'>Change Control No.<o:p></o:p></span></p></td> <td width=147 valign=top style='width:110.05pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:16.6pt'><br /> <p class=MsoNormal style='line-height:12.9pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width=141 valign=top style='width:105.95pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:16.6pt'><br /> <p class=MsoNormal style='line-height:12.9pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p><br /> </td> <td width=150 valign=top style='width:112.5pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:16.6pt'><br /> <p class=MsoNormal style='line-height:12.9pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> </tr> <tr style='mso-yfti-irow:2;height:16.6pt'> <td width=168 valign=top style='width:1.75in;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:16.6pt'><br /> <p class=MsoNormal style='line-height:12.9pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'>Stage/Document<o:p></o:p></span></p><br /> </td> <td width=147 valign=top style='width:110.05pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:16.6pt'><br /> <p class=MsoNormal style='line-height:12.9pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width=141 valign=top style='width:105.95pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:16.6pt'><br /> <p class=MsoNormal style='line-height:12.9pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width=150 valign=top style='width:112.5pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:16.6pt'><br /> <p class=MsoNormal style='line-height:12.9pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p><br /> </td> </tr> <tr style='mso-yfti-irow:3;height:16.6pt'> <td width=168 valign=top style='width:1.75in;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:16.6pt'><br /> <p class=MsoNormal style='line-height:12.9pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'>Manufacturing Date<o:p></o:p></span></p></td> <td width=147 valign=top style='width:110.05pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:16.6pt'><br /> <p class=MsoNormal style='line-height:12.9pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p><br /> </td> <td width=141 valign=top style='width:105.95pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:16.6pt'><br /> <p class=MsoNormal style='line-height:12.9pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width=150 valign=top style='width:112.5pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:16.6pt'><br /> <p class=MsoNormal style='line-height:12.9pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> </tr> <tr style='mso-yfti-irow:4;height:11.2pt'> <td width=168 valign=top style='width:1.75in;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:11.2pt'><br /> <p class=MsoNormal style='mso-line-height-alt:11.2pt'><span style='font-family: inherit;mso-bidi-font-family:"Times New Roman"'>Implementation Date<o:p></o:p></span></p></td> <td width=147 valign=top style='width:110.05pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:11.2pt'><br /> <p class=MsoNormal style='line-height:12.9pt'><span style='font-size:11.0pt; mso-bidi-font-size:12.0pt;font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width=141 valign=top style='width:105.95pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:11.2pt'><br /> <p class=MsoNormal style='line-height:12.9pt'><span style='font-size:11.0pt; mso-bidi-font-size:12.0pt;font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p><br /> </td> <td width=150 valign=top style='width:112.5pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:11.2pt'><br /> <p class=MsoNormal style='line-height:12.9pt'><span style='font-size:11.0pt; mso-bidi-font-size:12.0pt;font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> </tr> <tr style='mso-yfti-irow:5'> <td width=30 valign=top style='width:22.5pt;border:solid windowtext 1.0pt; border-top:none;padding:0in 5.4pt 0in 5.4pt'><br /> <p class=MsoNormal style='line-height:12.9pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'>2.<o:p></o:p></span></p><br /> </td> <td width=168 valign=top style='width:1.75in;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt'><br /> <p class=MsoNormal style='line-height:12.9pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'>Present Process/Use*<o:p></o:p></span></p><p class=MsoNormal style='line-height:12.9pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p><p class=MsoNormal style='line-height:12.9pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'>                                                                                                <o:p></o:p></span></p></td> <td width=438 colspan=3 valign=top style='width:328.5pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt'><br /> <p class=MsoNormal style='line-height:12.9pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'>                                                                                                                    <br /> <br />                                                                                                                 <o:p></o:p></span></p><p class=MsoNormal style='line-height:15.6pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p><p class=MsoNormal style='line-height:15.6pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p><p class=MsoNormal style='line-height:15.6pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p><p class=MsoNormal style='line-height:15.6pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'>                                               <br />          Modification:<br /> Major/Minor          <br />                                                                    <o:p></o:p></span></p></td> </tr> <tr style='mso-yfti-irow:6'> <td width=30 valign=top style='width:22.5pt;border:solid windowtext 1.0pt; border-top:none;padding:0in 5.4pt 0in 5.4pt'><br /> <p class=MsoNormal style='line-height:12.9pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'>3.<o:p></o:p></span></p></td> <td width=168 valign=top style='width:1.75in;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt'><br /> <p class=MsoNormal style='line-height:12.9pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'>Proposed Process/Use*<o:p></o:p></span></p><p class=MsoNormal style='line-height:12.9pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p><br /> <p class=MsoNormal style='line-height:12.9pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p><p class=MsoNormal style='line-height:12.9pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width=438 colspan=3 valign=top style='width:328.5pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt'><br /> <p class=MsoNormal style='line-height:12.9pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'>               <br />                                                                                                                                                                                                  <o:p></o:p></span></p><p class=MsoNormal style='line-height:15.6pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p><p class=MsoNormal style='line-height:15.6pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p><p class=MsoNormal style='line-height:15.6pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> </tr> <tr style='mso-yfti-irow:7'> <td width=30 valign=top style='width:22.5pt;border:solid windowtext 1.0pt; border-top:none;padding:0in 5.4pt 0in 5.4pt'><br /> <p class=MsoNormal style='line-height:12.9pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'>4.<o:p></o:p></span></p></td> <td width=168 valign=top style='width:1.75in;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt'><br /> <br /> <p class=MsoNormal style='line-height:12.9pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'>Justification/Impact of Change*<o:p></o:p></span></p><p class=MsoNormal style='line-height:12.9pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p><p class=MsoNormal style='line-height:12.9pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width=438 colspan=3 valign=top style='width:328.5pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt'><br /> <p class=MsoNormal style='line-height:12.9pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> </tr> <tr style='mso-yfti-irow:8'> <td width=30 valign=top style='width:22.5pt;border:solid windowtext 1.0pt; border-top:none;padding:0in 5.4pt 0in 5.4pt'><br /> <p class=MsoNormal style='line-height:12.9pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'>5.<o:p></o:p></span></p></td> <td width=168 valign=top style='width:1.75in;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt'><br /> <p class=MsoNormal style='line-height:12.9pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'>Supporting Data(If Required)<o:p></o:p></span></p><p class=MsoNormal style='line-height:12.9pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p><p class=MsoNormal style='line-height:12.9pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p><br /> </td> <td width=438 colspan=3 valign=top style='width:328.5pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt'><br /> <p class=MsoNormal style='line-height:12.9pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p><p class=MsoNormal style='line-height:15.6pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p><p class=MsoNormal style='line-height:15.6pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'>                         <br />    Enclosed/Not Enclosed<o:p></o:p></span></p></td> </tr> <tr style='mso-yfti-irow:9'> <td width=30 valign=top style='width:22.5pt;border:solid windowtext 1.0pt; border-top:none;padding:0in 5.4pt 0in 5.4pt'><br /> <p class=MsoNormal style='line-height:12.9pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'>6.<o:p></o:p></span></p></td> <td width=168 valign=top style='width:1.75in;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt'><br /> <p class=MsoNormal style='line-height:12.9pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'>Accepted <span class=SpellE>Crieteria</span><o:p></o:p></span></p><p class=MsoNormal style='line-height:12.9pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p><br /> <p class=MsoNormal style='line-height:12.9pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p><p class=MsoNormal style='line-height:12.9pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width=438 colspan=3 valign=top style='width:328.5pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt'><br /> <p class=MsoNormal style='line-height:12.9pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> </tr> <tr style='mso-yfti-irow:10;mso-yfti-lastrow:yes'> <td width=30 valign=top style='width:22.5pt;border:solid windowtext 1.0pt; border-top:none;padding:0in 5.4pt 0in 5.4pt'><br /> <br /> <p class=MsoNormal style='line-height:12.9pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'>7.<o:p></o:p></span></p></td> <td width=606 colspan=4 valign=top style='width:454.5pt;border-top:none; border-left:none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt'><br /> <p class=MsoNormal style='line-height:12.9pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'>                   <o:p></o:p></span></p><p class=MsoNormal style='line-height:12.9pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'>         <br />  Signature:<br /> ________________                         <br /> ___________________<o:p></o:p></span></p><br /> <p class=MsoNormal style='line-height:12.9pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'>                      <br /> (Officer/Executive/Designee)           <br /> (Head – Initiating Department)<o:p></o:p></span></p><p class=MsoNormal style='line-height:12.9pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'>         <br />          Date: _________________<br />                         ____________________ <br />        <o:p></o:p></span></p></td> </tr> </table><br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-size:9.0pt; font-family:Verdana;mso-bidi-font-family:"Times New Roman";color:#333333; display:none;mso-hide:all'><o:p> </o:p></span></p><br /> <table class=MsoNormalTable border=0 cellspacing=0 cellpadding=0 width=524 style='width:393.3pt;margin-left:.2in;border-collapse:collapse;mso-padding-alt: 0in 0in 0in 0in'><tr style='mso-yfti-irow:0;mso-yfti-firstrow:yes;page-break-inside:avoid; height:12.3pt'> <td width="5%" rowspan=6 valign=top style='width:5.0%;border:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.3pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'>8.<o:p></o:p></span></p></td> <td width="94%" colspan=5 valign=top style='width:94.0%;border-top:solid windowtext 1.0pt; border-left:none;border-bottom:none;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.3pt'><br /> <br /> <p class=MsoNormal style='line-height:15.6pt'><b><u><span style='font-family: inherit;mso-bidi-font-family:"Times New Roman"'>Comments from F&D<br /> Department*(if required)</span></u></b><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p></td> </tr> <tr style='mso-yfti-irow:1;page-break-inside:avoid;height:12.3pt'> <td width="27%" valign=top style='width:27.0%;padding:0in 0in 0in 0in; height:12.3pt'><br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width="31%" colspan=2 valign=top style='width:31.0%;padding:0in 0in 0in 0in; height:12.3pt'><br /> <br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width="17%" valign=top style='width:17.0%;padding:0in 5.4pt 0in 5.4pt; height:12.3pt'><br /> <p class=MsoNormal align=right style='text-align:right;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width="18%" valign=top style='width:18.0%;border:none;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.3pt'><br /> <p class=MsoNormal align=right style='text-align:right;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> </tr> <tr style='mso-yfti-irow:2;page-break-inside:avoid;height:12.3pt'> <td width="27%" valign=top style='width:27.0%;padding:0in 0in 0in 0in; height:12.3pt'><br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width="31%" colspan=2 valign=top style='width:31.0%;padding:0in 0in 0in 0in; height:12.3pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width="17%" valign=top style='width:17.0%;padding:0in 5.4pt 0in 5.4pt; height:12.3pt'><br /> <p class=MsoNormal align=right style='text-align:right;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p><br /> <p class=MsoNormal align=right style='text-align:right;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p><p class=MsoNormal align=right style='text-align:right;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width="18%" valign=top style='width:18.0%;border:none;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.3pt'><br /> <p class=MsoNormal align=right style='text-align:right;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> </tr> <tr style='mso-yfti-irow:3;page-break-inside:avoid;height:12.3pt'> <td width="27%" valign=top style='width:27.0%;padding:0in 0in 0in 0in; height:12.3pt'><br /> <br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width="31%" colspan=2 valign=top style='width:31.0%;padding:0in 0in 0in 0in; height:12.3pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width="17%" valign=top style='width:17.0%;padding:0in 5.4pt 0in 5.4pt; height:12.3pt'><br /> <p class=MsoNormal align=right style='text-align:right;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'>Modification:<o:p></o:p></span></p></td> <td width="18%" valign=top style='width:18.0%;border:none;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.3pt'><br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'>Major/Minor<o:p></o:p></span></p></td> </tr> <tr style='mso-yfti-irow:4;page-break-inside:avoid;height:12.3pt'> <td width="27%" valign=top style='width:27.0%;padding:0in 0in 0in 0in; height:12.3pt'><br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width="31%" colspan=2 valign=top style='width:31.0%;border:none; border-bottom:solid windowtext 1.0pt;padding:0in 0in 0in 0in;height:12.3pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width="17%" valign=top style='width:17.0%;padding:0in 5.4pt 0in 5.4pt; height:12.3pt'><br /> <p class=MsoNormal align=right style='text-align:right;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'>Date:<o:p></o:p></span></p></td> <td width="18%" valign=top style='width:18.0%;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.3pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p><br /> </td> </tr> <tr style='mso-yfti-irow:5;page-break-inside:avoid;height:12.3pt'> <td width="27%" valign=top style='width:27.0%;border:none;border-bottom:solid windowtext 1.0pt; padding:0in 0in 0in 0in;height:12.3pt'><br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'>Signature<o:p></o:p></span></p></td> <td width="31%" colspan=2 valign=top style='width:31.0%;border:none; border-bottom:solid windowtext 1.0pt;padding:0in 0in 0in 0in;height:12.3pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'>Manager-F&D<o:p></o:p></span></p><br /> </td> <td width="17%" valign=top style='width:17.0%;border:none;border-bottom:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.3pt'><br /> <p class=MsoNormal align=right style='text-align:right;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width="18%" valign=top style='width:18.0%;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.3pt'><br /> <p class=MsoNormal align=right style='text-align:right;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> </tr> <tr style='mso-yfti-irow:6;page-break-inside:avoid;height:12.3pt'> <td width="5%" rowspan=10 valign=top style='width:5.0%;border:solid windowtext 1.0pt; border-top:none;padding:0in 5.4pt 0in 5.4pt;height:12.3pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'>9.<o:p></o:p></span></p></td> <td width="94%" colspan=5 valign=top style='width:94.0%;border:none; border-right:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:12.3pt'><br /> <p class=MsoNormal style='line-height:15.6pt'><b><u><span style='font-family: inherit;mso-bidi-font-family:"Times New Roman"'>Comments from Quality<br /> Assurance Department*</span></u></b><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p></td> </tr> <tr style='mso-yfti-irow:7;page-break-inside:avoid;height:12.3pt'> <td width="27%" valign=top style='width:27.0%;padding:0in 0in 0in 0in; height:12.3pt'><br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width="31%" colspan=2 valign=top style='width:31.0%;padding:0in 0in 0in 0in; height:12.3pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width="17%" valign=top style='width:17.0%;padding:0in 5.4pt 0in 5.4pt; height:12.3pt'><br /> <p class=MsoNormal align=right style='text-align:right;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'>Modification:<o:p></o:p></span></p><br /> </td> <td width="18%" valign=top style='width:18.0%;border:none;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.3pt'><br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'>Major/Minor<o:p></o:p></span></p><p class=MsoNormal style='line-height:15.6pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> </tr> <tr style='mso-yfti-irow:8;page-break-inside:avoid;height:12.3pt'> <td width="58%" colspan=3 valign=top style='width:58.0%;padding:0in 5.4pt 0in 5.4pt; height:12.3pt'><br /> <br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'>Regulatory Notification / approval<o:p></o:p></span></p></td> <td width="35%" colspan=2 valign=top style='width:35.0%;border:none; border-right:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:12.3pt'><br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'>          <br /> Required / Not Required<o:p></o:p></span></p></td> </tr> <tr style='mso-yfti-irow:9;page-break-inside:avoid;height:12.3pt'> <td width="58%" colspan=3 valign=top style='width:58.0%;padding:0in 0in 0in 0in; height:12.3pt'><br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p><p class=MsoNormal style='line-height:15.6pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'>Type of analysis to be carried out<br /> (if any extra analysis is required, give details):<o:p></o:p></span></p><p class=MsoNormal style='line-height:15.6pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p><p class=MsoNormal style='line-height:15.6pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width="17%" valign=top style='width:17.0%;padding:0in 5.4pt 0in 5.4pt; height:12.3pt'><br /> <p class=MsoNormal align=right style='text-align:right;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p><br /> </td> <td width="18%" valign=top style='width:18.0%;border:none;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.3pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> </tr> <tr style='mso-yfti-irow:10;page-break-inside:avoid;height:12.3pt'> <td width="27%" valign=top style='width:27.0%;padding:0in 0in 0in 0in; height:12.3pt'><br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width="31%" colspan=2 valign=top style='width:31.0%;padding:0in 0in 0in 0in; height:12.3pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width="17%" valign=top style='width:17.0%;padding:0in 5.4pt 0in 5.4pt; height:12.3pt'><br /> <p class=MsoNormal align=right style='text-align:right;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width="18%" valign=top style='width:18.0%;border:none;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.3pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> </tr> <tr style='mso-yfti-irow:11;page-break-inside:avoid;height:12.3pt'> <td width="27%" valign=top style='width:27.0%;padding:0in 5.4pt 0in 5.4pt; height:12.3pt'><br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'>Subsequent Stages<o:p></o:p></span></p></td> <td width="48%" colspan=3 valign=top style='width:48.0%;padding:0in 5.4pt 0in 5.4pt; height:12.3pt'><br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'>Will be controlled/Not controlled<o:p></o:p></span></p></td> <td width="18%" valign=top style='width:18.0%;border:none;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.3pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> </tr> <tr style='mso-yfti-irow:12;page-break-inside:avoid;height:12.3pt'> <td width="27%" valign=top style='width:27.0%;padding:0in 0in 0in 0in; height:12.3pt'><br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width="31%" colspan=2 valign=top style='width:31.0%;padding:0in 0in 0in 0in; height:12.3pt'><br /> <br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width="17%" valign=top style='width:17.0%;padding:0in 5.4pt 0in 5.4pt; height:12.3pt'><br /> <p class=MsoNormal align=right style='text-align:right;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width="18%" valign=top style='width:18.0%;border:none;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.3pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> </tr> <tr style='mso-yfti-irow:13;page-break-inside:avoid;height:12.3pt'> <td width="27%" valign=top style='width:27.0%;padding:0in 0in 0in 0in; height:12.3pt'><br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'>Validation Status<o:p></o:p></span></p></td> <td width="31%" colspan=2 valign=top style='width:31.0%;padding:0in 0in 0in 0in; height:12.3pt'><br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'>Will affected / not affected<o:p></o:p></span></p></td> <td width="17%" valign=top style='width:17.0%;padding:0in 5.4pt 0in 5.4pt; height:12.3pt'><br /> <br /> <p class=MsoNormal align=right style='text-align:right;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width="18%" valign=top style='width:18.0%;border:none;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.3pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> </tr> <tr style='mso-yfti-irow:14;page-break-inside:avoid;height:12.3pt'> <td width="27%" valign=top style='width:27.0%;padding:0in 0in 0in 0in; height:12.3pt'><br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p><br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width="31%" colspan=2 valign=top style='width:31.0%;border:none; border-bottom:solid windowtext 1.0pt;padding:0in 0in 0in 0in;height:12.3pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width="17%" valign=top style='width:17.0%;padding:0in 5.4pt 0in 5.4pt; height:12.3pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'>             <br /> Date:<o:p></o:p></span></p><br /> </td> <td width="18%" valign=top style='width:18.0%;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.3pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> </tr> <tr style='mso-yfti-irow:15;page-break-inside:avoid;height:12.3pt'> <td width="27%" valign=top style='width:27.0%;border:none;border-bottom:solid windowtext 1.0pt; padding:0in 0in 0in 0in;height:12.3pt'><br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'>Signature<o:p></o:p></span></p><br /> </td> <td width="31%" colspan=2 valign=top style='width:31.0%;border:none; border-bottom:solid windowtext 1.0pt;padding:0in 0in 0in 0in;height:12.3pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'>Manager -<br /> QA<o:p></o:p></span></p></td> <td width="17%" valign=top style='width:17.0%;border:none;border-bottom:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.3pt'><br /> <p class=MsoNormal align=right style='text-align:right;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width="18%" valign=top style='width:18.0%;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.3pt'><br /> <br /> <p class=MsoNormal align=right style='text-align:right;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> </tr> <tr style='mso-yfti-irow:16;page-break-inside:avoid;height:12.3pt'> <td width="5%" rowspan=4 valign=top style='width:5.0%;border:solid windowtext 1.0pt; border-top:none;padding:0in 5.4pt 0in 5.4pt;height:12.3pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'>10.<o:p></o:p></span></p></td> <td width="94%" colspan=5 valign=top style='width:94.0%;border:none; border-right:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:12.3pt'><br /> <br /> <p class=MsoNormal style='line-height:15.6pt'><b><u><span style='font-family: inherit;mso-bidi-font-family:"Times New Roman"'>Comments from Regulatory<br /> Affairs Department*(if required)</span></u></b><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p><p class=MsoNormal style='line-height:15.6pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> </tr> <tr style='mso-yfti-irow:17;page-break-inside:avoid;height:12.3pt'> <td width="94%" colspan=5 valign=top style='width:94.0%;border:none; border-right:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:12.3pt'><br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'>Proposed Change is recommended/ Not<br /> recommended<o:p></o:p></span></p><p class=MsoNormal style='line-height:15.6pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'>           <o:p></o:p></span></p><br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p><p class=MsoNormal style='line-height:15.6pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> </tr> <tr style='mso-yfti-irow:18;page-break-inside:avoid;height:12.3pt'> <td width="27%" valign=top style='width:27.0%;padding:0in 0in 0in 0in; height:12.3pt'><br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width="31%" colspan=2 valign=top style='width:31.0%;border:none; border-bottom:solid windowtext 1.0pt;padding:0in 0in 0in 0in;height:12.3pt'><br /> <br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width="17%" valign=top style='width:17.0%;padding:0in 5.4pt 0in 5.4pt; height:12.3pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'>           <br /> Date:<o:p></o:p></span></p></td> <td width="18%" valign=top style='width:18.0%;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.3pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p><br /> </td> </tr> <tr style='mso-yfti-irow:19;page-break-inside:avoid;height:12.3pt'> <td width="27%" valign=top style='width:27.0%;border:none;border-bottom:solid windowtext 1.0pt; padding:0in 0in 0in 0in;height:12.3pt'><br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'>Signature<o:p></o:p></span></p></td> <td width="31%" colspan=2 valign=top style='width:31.0%;border:none; border-bottom:solid windowtext 1.0pt;padding:0in 0in 0in 0in;height:12.3pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'>Manager –<br /> RA<o:p></o:p></span></p><br /> </td> <td width="17%" valign=top style='width:17.0%;border:none;border-bottom:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.3pt'><br /> <p class=MsoNormal align=right style='text-align:right;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width="18%" valign=top style='width:18.0%;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.3pt'><br /> <p class=MsoNormal align=right style='text-align:right;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> </tr> <tr style='mso-yfti-irow:20;page-break-inside:avoid;height:12.3pt'> <td width="5%" rowspan=4 valign=top style='width:5.0%;border:solid windowtext 1.0pt; border-top:none;padding:0in 5.4pt 0in 5.4pt;height:12.3pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'>11.<o:p></o:p></span></p></td> <td width="94%" colspan=5 valign=top style='width:94.0%;border:none; border-right:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:12.3pt'><br /> <p class=MsoNormal style='line-height:15.6pt'><b><u><span style='font-family: inherit;mso-bidi-font-family:"Times New Roman"'>Comments from Engineering<br /> Department* (If required)</span></u></b><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p><p class=MsoNormal style='line-height:15.6pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> </tr> <tr style='mso-yfti-irow:21;page-break-inside:avoid;height:12.3pt'> <td width="27%" valign=top style='width:27.0%;padding:0in 0in 0in 0in; height:12.3pt'><br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width="31%" colspan=2 valign=top style='width:31.0%;padding:0in 0in 0in 0in; height:12.3pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width="17%" valign=top style='width:17.0%;padding:0in 5.4pt 0in 5.4pt; height:12.3pt'><br /> <p class=MsoNormal align=right style='text-align:right;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p><br /> </td> <td width="18%" valign=top style='width:18.0%;border:none;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.3pt'><br /> <p class=MsoNormal align=right style='text-align:right;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> </tr> <tr style='mso-yfti-irow:22;page-break-inside:avoid;height:12.3pt'> <td width="27%" valign=top style='width:27.0%;padding:0in 0in 0in 0in; height:12.3pt'><br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width="31%" colspan=2 valign=top style='width:31.0%;border:none; border-bottom:solid windowtext 1.0pt;padding:0in 0in 0in 0in;height:12.3pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width="17%" valign=top style='width:17.0%;padding:0in 5.4pt 0in 5.4pt; height:12.3pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'>             <br /> Date:<o:p></o:p></span></p></td> <td width="18%" valign=top style='width:18.0%;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.3pt'><br /> <br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> </tr> <tr style='mso-yfti-irow:23;page-break-inside:avoid;height:12.3pt'> <td width="27%" valign=top style='width:27.0%;border:none;border-bottom:solid windowtext 1.0pt; padding:0in 0in 0in 0in;height:12.3pt'><br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'>Signature<o:p></o:p></span></p></td> <td width="31%" colspan=2 valign=top style='width:31.0%;border:none; border-bottom:solid windowtext 1.0pt;padding:0in 0in 0in 0in;height:12.3pt'><br /> <br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'>Manager -<br /> Engineering<o:p></o:p></span></p></td> <td width="17%" valign=top style='width:17.0%;border:none;border-bottom:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.3pt'><br /> <p class=MsoNormal align=right style='text-align:right;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width="18%" valign=top style='width:18.0%;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.3pt'><br /> <p class=MsoNormal align=right style='text-align:right;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> </tr> <tr style='mso-yfti-irow:24;page-break-inside:avoid;height:12.3pt'> <td width="5%" rowspan=5 valign=top style='width:5.0%;border:solid windowtext 1.0pt; border-top:none;padding:0in 5.4pt 0in 5.4pt;height:12.3pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'>12.<o:p></o:p></span></p></td> <td width="94%" colspan=5 valign=top style='width:94.0%;border:none; border-right:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:12.3pt'><br /> <p class=MsoNormal style='line-height:15.6pt'><b><u><span style='font-family: inherit;mso-bidi-font-family:"Times New Roman"'>Comments</span></u></b><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p></td> </tr> <tr style='mso-yfti-irow:25;page-break-inside:avoid;height:12.3pt'> <td width="35%" colspan=2 valign=top style='width:35.0%;padding:0in 0in 0in 0in; height:12.3pt'><br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width="23%" valign=top style='width:23.0%;padding:0in 5.4pt 0in 5.4pt; height:12.3pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width="17%" valign=top style='width:17.0%;padding:0in 5.4pt 0in 5.4pt; height:12.3pt'><br /> <br /> <p class=MsoNormal align=right style='text-align:right;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width="18%" valign=top style='width:18.0%;border:none;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.3pt'><br /> <p class=MsoNormal align=right style='text-align:right;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> </tr> <tr style='mso-yfti-irow:26;page-break-inside:avoid;height:12.3pt'> <td width="35%" colspan=2 valign=top style='width:35.0%;padding:0in 0in 0in 0in; height:12.3pt'><br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p><br /> </td> <td width="23%" valign=top style='width:23.0%;padding:0in 5.4pt 0in 5.4pt; height:12.3pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width="35%" colspan=2 valign=top style='width:35.0%;border:none; border-right:solid windowtext 1.0pt;padding:0in 5.4pt 0in 5.4pt;height:12.3pt'><br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p><p class=MsoNormal style='line-height:15.6pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p><p class=MsoNormal style='line-height:15.6pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p><p class=MsoNormal style='line-height:15.6pt'><span class=SpellE><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'>Authorised</span></span><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'> / Not <span class=SpellE>authorised</span><o:p></o:p></span></p><br /> </td> </tr> <tr style='mso-yfti-irow:27;page-break-inside:avoid;height:12.3pt'> <td width="35%" colspan=2 valign=top style='width:35.0%;padding:0in 0in 0in 0in; height:12.3pt'><br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'>           <br />      <o:p></o:p></span></p></td> <td width="23%" valign=top style='width:23.0%;border:none;border-bottom:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.3pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p><br /> </td> <td width="17%" valign=top style='width:17.0%;padding:0in 5.4pt 0in 5.4pt; height:12.3pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'>           <br /> Date:<o:p></o:p></span></p></td> <td width="18%" valign=top style='width:18.0%;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.3pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> </tr> <tr style='mso-yfti-irow:28;page-break-inside:avoid;height:12.3pt'> <td width="35%" colspan=2 valign=top style='width:35.0%;border:none; border-bottom:solid windowtext 1.0pt;padding:0in 0in 0in 0in;height:12.3pt'><br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'>Signature:    <br /> Plant Head<o:p></o:p></span></p></td> <td width="23%" valign=top style='width:23.0%;border:none;border-bottom:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.3pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'>Site<br /> Quality Head<o:p></o:p></span></p><br /> </td> <td width="17%" valign=top style='width:17.0%;border:none;border-bottom:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.3pt'><br /> <p class=MsoNormal align=right style='text-align:right;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width="18%" valign=top style='width:18.0%;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:12.3pt'><br /> <p class=MsoNormal align=right style='text-align:right;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> </tr> <tr style='mso-yfti-irow:29;page-break-inside:avoid;height:12.3pt'> <td width="100%" colspan=6 valign=top style='width:100.0%;border:solid windowtext 1.0pt; border-top:none;padding:0in 5.4pt 0in 5.4pt;height:12.3pt'><br /> <p class=MsoNormal style='line-height:15.6pt'><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman"'>*Whenever applicable, append<br /> supporting documentation.<br />                                   <o:p></o:p></span></p></td> </tr> <tr style='mso-yfti-irow:30;mso-yfti-lastrow:yes'> <td width=38 style='width:28.5pt;padding:0in 0in 0in 0in'><br /> <p class=MsoNormal><span style='font-size:.5pt;mso-bidi-font-size:12.0pt; font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width=194 style='width:145.5pt;padding:0in 0in 0in 0in'><br /> <p class=MsoNormal><span style='font-size:.5pt;mso-bidi-font-size:12.0pt; font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width=53 style='width:39.75pt;padding:0in 0in 0in 0in'><br /> <p class=MsoNormal><span style='font-size:.5pt;mso-bidi-font-size:12.0pt; font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width=165 style='width:123.75pt;padding:0in 0in 0in 0in'><br /> <p class=MsoNormal><span style='font-size:.5pt;mso-bidi-font-size:12.0pt; font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width=120 style='width:1.25in;padding:0in 0in 0in 0in'><br /> <p class=MsoNormal><span style='font-size:.5pt;mso-bidi-font-size:12.0pt; font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width=133 style='width:99.75pt;padding:0in 0in 0in 0in'><br /> <p class=MsoNormal><span style='font-size:.5pt;mso-bidi-font-size:12.0pt; font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> </tr> </table><br /> <p class=MsoNormal style='line-height:15.6pt'><b><span style='font-family:inherit; mso-bidi-font-family:"Times New Roman";color:#333333'>                                                                      </span></b><span style='font-size:9.0pt;font-family:inherit;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p></o:p></span></p><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><b><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman";color:#333333; letter-spacing:1.5pt'>  </span></b><span style='font-size:9.0pt; font-family:inherit;mso-bidi-font-family:"Times New Roman";color:#333333'><o:p></o:p></span></p><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-size:9.0pt;font-family:inherit;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p> </o:p></span></p><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><b><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman";color:#333333; letter-spacing:1.5pt'>Change Control Record</span></b><span style='font-size: 9.0pt;font-family:inherit;mso-bidi-font-family:"Times New Roman";color:#333333'><o:p></o:p></span></p><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-size:9.0pt;font-family:inherit;mso-bidi-font-family:"Times New Roman"; color:#333333'><o:p> </o:p></span></p><br /> <table class=MsoNormalTable border=0 cellspacing=0 cellpadding=0 style='margin-left:.2in;border-collapse:collapse;mso-padding-alt:0in 0in 0in 0in'><tr style='mso-yfti-irow:0;mso-yfti-firstrow:yes;height:28.15pt'> <td width=36 valign=top style='width:27.0pt;border:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:28.15pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><b><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'>S.N</span></b><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p><br /> </td> <td width=43 valign=top style='width:31.9pt;border:solid windowtext 1.0pt; border-left:none;padding:0in 5.4pt 0in 5.4pt;height:28.15pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><b><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'>Date</span></b><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p></td> <td width=55 valign=top style='width:41.2pt;border:solid windowtext 1.0pt; border-left:none;padding:0in 5.4pt 0in 5.4pt;height:28.15pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><b><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'>Change<br /> Control no.</span></b><span style='font-family:inherit;mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p></td> <td width=84 valign=top style='width:63.05pt;border:solid windowtext 1.0pt; border-left:none;padding:0in 5.4pt 0in 5.4pt;height:28.15pt'><br /> <br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><b><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'>Originating</span></b><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p><p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><b><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'>Dept</span></b><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p></td> <td width=76 valign=top style='width:57.3pt;border:solid windowtext 1.0pt; border-left:none;padding:0in 5.4pt 0in 5.4pt;height:28.15pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><b><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'>Product /<br /> Document</span></b><span style='font-family:inherit;mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p></td> <td width=48 valign=top style='width:36.3pt;border:solid windowtext 1.0pt; border-left:none;padding:0in 5.4pt 0in 5.4pt;height:28.15pt'><br /> <br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><b><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'>Stage</span></b><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p></td> <td width=68 valign=top style='width:50.85pt;border:solid windowtext 1.0pt; border-left:none;padding:0in 5.4pt 0in 5.4pt;height:28.15pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><b><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'>Details of<br /> Change</span></b><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p></td> <td width=109 valign=top style='width:81.45pt;border:solid windowtext 1.0pt; border-left:none;padding:0in 5.4pt 0in 5.4pt;height:28.15pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><b><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'>Date of<br /> Implementation</span></b><span style='font-family:inherit;mso-bidi-font-family: "Times New Roman"'><o:p></o:p></span></p><br /> </td> <td width=50 valign=top style='width:37.75pt;border:solid windowtext 1.0pt; border-left:none;padding:0in 5.4pt 0in 5.4pt;height:28.15pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><b><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'>Status</span></b><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p></td> <td width=69 valign=top style='width:51.6pt;border:solid windowtext 1.0pt; border-left:none;padding:0in 5.4pt 0in 5.4pt;height:28.15pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><b><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'>Remarks</span></b><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p></o:p></span></p></td> </tr> <tr style='mso-yfti-irow:1;height:13.65pt'> <td width=36 valign=top style='width:27.0pt;border:solid windowtext 1.0pt; border-top:none;padding:0in 5.4pt 0in 5.4pt;height:13.65pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width=43 valign=top style='width:31.9pt;border-top:none;border-left:none; border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:13.65pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width=55 valign=top style='width:41.2pt;border-top:none;border-left:none; border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:13.65pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p><br /> </td> <td width=84 valign=top style='width:63.05pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:13.65pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width=76 valign=top style='width:57.3pt;border-top:none;border-left:none; border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:13.65pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width=48 valign=top style='width:36.3pt;border-top:none;border-left:none; border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:13.65pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p><br /> </td> <td width=68 valign=top style='width:50.85pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:13.65pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width=109 valign=top style='width:81.45pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:13.65pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width=50 valign=top style='width:37.75pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:13.65pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p><br /> </td> <td width=69 valign=top style='width:51.6pt;border-top:none;border-left:none; border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:13.65pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> </tr> <tr style='mso-yfti-irow:2;height:14.55pt'> <td width=36 valign=top style='width:27.0pt;border:solid windowtext 1.0pt; border-top:none;padding:0in 5.4pt 0in 5.4pt;height:14.55pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width=43 valign=top style='width:31.9pt;border-top:none;border-left:none; border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:14.55pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width=55 valign=top style='width:41.2pt;border-top:none;border-left:none; border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:14.55pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width=84 valign=top style='width:63.05pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:14.55pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width=76 valign=top style='width:57.3pt;border-top:none;border-left:none; border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:14.55pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width=48 valign=top style='width:36.3pt;border-top:none;border-left:none; border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:14.55pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width=68 valign=top style='width:50.85pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:14.55pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width=109 valign=top style='width:81.45pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:14.55pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width=50 valign=top style='width:37.75pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:14.55pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width=69 valign=top style='width:51.6pt;border-top:none;border-left:none; border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:14.55pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> </tr> <tr style='mso-yfti-irow:3;mso-yfti-lastrow:yes;height:14.55pt'> <td width=36 valign=top style='width:27.0pt;border:solid windowtext 1.0pt; border-top:none;padding:0in 5.4pt 0in 5.4pt;height:14.55pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width=43 valign=top style='width:31.9pt;border-top:none;border-left:none; 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border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:14.55pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width=48 valign=top style='width:36.3pt;border-top:none;border-left:none; border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:14.55pt'><br /> <br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width=68 valign=top style='width:50.85pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:14.55pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width=109 valign=top style='width:81.45pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:14.55pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width=50 valign=top style='width:37.75pt;border-top:none;border-left: none;border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:14.55pt'><br /> <br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> <td width=69 valign=top style='width:51.6pt;border-top:none;border-left:none; border-bottom:solid windowtext 1.0pt;border-right:solid windowtext 1.0pt; padding:0in 5.4pt 0in 5.4pt;height:14.55pt'><br /> <p class=MsoNormal align=center style='text-align:center;line-height:15.6pt'><span style='font-family:inherit;mso-bidi-font-family:"Times New Roman"'><o:p> </o:p></span></p></td> </tr> </table><br /> <p class=MsoNormal><o:p> </o:p></p><br /> </div><br /> </body><br /> <br /> </html>http://scholarpharma.blogspot.com/2012/01/sd.html0margipatel02@gmail.com (margipatel02@gmail.com)tag:blogger.com,1999:blog-8563020669307343167.post-7998020144328996057Sun, 01 Jan 2012 07:03:00 +00002011-12-31T23:03:23.558-08:00Clinical Trials<b>Clinical Trials </b> Introduction Clinical trials are a means of developing new treatments and medications for diseases and conditions. There are strict rules for clinical trials, which are monitored by the National Institutes of Health and the U.S Food and Drug Administration. Clinical trials are also called clinical studies, research protocols or medical research and often compare one drug against another to see which is more effective, or the medicine or procedure in a specific demographic group or for a specific disease. About Clinical Trials Why Participate in a Clinical Trial? Participants in clinical trials can play a more active role in their health care, gain access to new research treatments before they are widely available and help others by contributing to medical research. Where Do the Ideas for Trials Come from? Ideas for clinical trials usually come from researchers. After researchers test new therapies or procedures in the laboratory and/or in animal studies, the treatments with the most promising test results are moved into clinical trials. During a trial, more and more information is gained about a new treatment, its risks and how well it may or may not work. Who Sponsors Clinical Trials? Clinical trials are sponsored or funded by a variety of organizations or individuals such as physicians, medical institutions, foundations, voluntary medical-related groups and pharmaceutical companies, in addition to federal agencies such as the National Institutes of Health, the Department of Defense and the Department of Veteran’s Affairs. Trials can take place in a variety of locations, such as hospitals, universities, doctors’ offices or community clinics. What is a Protocol? A protocol is a study plan on which all clinical trials are based. The plan is carefully designed to safeguard the health of the participants as well as answer specific research questions. A protocol describes what types of people can participate in the trial; the schedule of tests, procedures, medications and dosages; and the length of the study. While in clinical trial, participants following a protocol are seen regularly by the research staff to monitor their health and to determine the safety and effectiveness of their treatment. What is a Placebo? A placebo is an inactive pill, liquid, or powder that has no treatment value. In clinical trials, experimental treatments are often compared with placebos to assess the treatment’s effectiveness. In some studies, the participants in the control group will receive a placebo instead of an active drug or treatment. What is a Control or Control Group? A control is the standard by which experimental observations are evaluated. In many clinical trials, one group of patients will be given an experimental drug or treatment, while the control group is given either a standard treatment for the illness or a placebo. What are the Different Types of Clinical Trials? Treatment trials test new treatments, new combinations of drugs, or new approaches to surgery or radiation therapy. Prevention trials look for better ways to prevent disease in people who have never had the disease or to prevent a disease from returning. These approaches may include medicine, vitamins, vaccines, minerals or lifestyle changes. Screening trials test the best way to detect certain diseases or health conditions. Quality of Life trials (or Supportive Care trials) explore ways to improve comfort and the equality of life for individuals with a chronic illness. Classification of Clinical Trials There are three types of clinical trials – phase I, phase II and phase III – each one is designed to learn something different about a new medical treatment. Phase I Trials A phase I trial is the first test of a new treatment, and it uses the fewest number of patients (20-30 patients is typical). A phase I trial for a new drug is designed to determine the safety of the new drug, how to best administer it and the correct dosage (i.e., one that will minimize undesirable side effects). Because investigators are very interested in how the drug behaves in the body, patients in a phase I trial undergo frequent monitoring of their vital signs. Although drugs being tested in a phase I trial have shown promise in the laboratory, there is no guarantee that the drug will have any positive effects on a patient. Patients participating in a phase I drug trial help advance basic medical knowledge; they may or may not reap any personal benefits. Phase II Trials After a phase I clinical trial has determined the safe dose of a drug, it can enter a phase II trial, which begins the process of determining the drug’s effectiveness in treating a specific type of disease. Because a phase II trial involves more patients than a phase I trial, physicians also have a chance to observe any less common side effects associated with the drug. In a phase II trial, which can involve 100 patients or more, physicians carefully monitor patients for a drug effect. For example, in a clinical trial testing a drug to increase the number of platelets in the blood, patients would have frequent blood samples taken, but they might also undergo several physical exams and other tests. The high level of patient monitoring in a phase II trial can be very time-consuming, so patients should take this into account when considering a phase II trial. If a drug in a phase II trial brings about a positive change in at least one-fifth of the patients, then it can be tested in a phase III trial. However, if the new drug has shown very positive effects in patients, the FDA also has the option of approving the drug for general use at this point. Phase III Trials A phase III trial involves the largest number of patients, typically several hundred, even thousands of patients. Phase III trials are randomized, which means that some of the patients in the trail are randomly chosen to receive the experimental treatment, while the others receive a standard treatment. The outcomes of the patients receiving the new treatment (the treatment group) are compared with the outcomes of the patients receiving the standard treatment (the control group). In some phase III trials (single-blind studies), patients do not know which control group they are in. In a double-blind study, the physicians also do not know which patients are in the treatment group and which are in the control group. Blinded studies are used to prevent biased study results. If a new drug successfully passes a phase III trial, the FDA will approve the drug for marketing to the general public.http://scholarpharma.blogspot.com/2011/12/clinical-trials.html0margipatel02@gmail.com (margipatel02@gmail.com)tag:blogger.com,1999:blog-8563020669307343167.post-7733080334295951743Sun, 01 Jan 2012 06:32:00 +00002011-12-31T22:32:18.482-08:00Preparation and Standardization of 0.1 M Disodium Edetate (EDTA)Preparation and Standardization of 0.1 M Disodium Edetate (EDTA)Preparation and Standardization of 0.1 M Disodium Edetate (EDTA) Preparation: · Take about 100 ml of water in a cleaned and dried 1000 ml volumetric flask. · Add about 37. 2 gm of Disodium edetate with continues stirring. · Add more about 700 ml of water mix. · Make up the volume 1000 ml with water. Mix solution thoroughly. · Keep the solution for atleast one hour and than carryout the standardization. Standardization: · Weigh accurately about 400 mg of Calcium Carbonate. · Previously dried at about 110°C for about 2 hour. · Transfer it in a cleaned and dried 500 ml conical flask and add about 10 ml of water with gentle stirring to form slurry. · Dissolve the carbonate in 2 ml of dilute hydrochloric acid and shake well until it dissolve. · Add 100 ml water through inner surface of the flask with the stirring of solution. · Add 30 ml of 0.1 M Disodium edetate (prepared) from the burette with constant stirring. · Add 15 ml of Sodium hydroxide solution with constant stirring. · Add 300 mg of hydroxy nephthol blue solution as a indicator. · Add 0.1 M Disodium edetate (Prepared) with constant stirring and titrate it until the solution gives blue colour. W x 1000 Molarity of 0.1 M Disodium edetate = ---------------------- BR x 100.09http://scholarpharma.blogspot.com/2011/12/preparation-and-standardization-of-01-m.html4margipatel02@gmail.com (margipatel02@gmail.com)tag:blogger.com,1999:blog-8563020669307343167.post-7042262669023768458Sun, 01 Jan 2012 06:29:00 +00002011-12-31T22:29:07.312-08:00Assay of Ascorbic acid<b>Assay of Ascorbic acid</b> Reagents Required: 1.0M Sulfuric acid 0.05M Iodine Procedure Weigh accurately about 0.1gm of sample and dissolve in a mixture of 100 ml freshly boiled and cooled water and 25ml of 1M sulfuric acid. Immediately Titrate with 0.05M iodine, using starch solution as indicator until a persistent blue-violet color is obtained. Each ml of 0.05M iodine is equivalent to 0.008806gm of ascorbic acid. Calculation: BR X Actual molarity X 0.008806 X 100 % of Ascorbic acid = ---------------------------------------------------- 0.05 X Wt. Of sample BR= Burette Readinghttp://scholarpharma.blogspot.com/2011/12/assay-of-ascorbic-acid.html1margipatel02@gmail.com (margipatel02@gmail.com)