CDER评审官指南《色谱分析方法的验证》CenterforDrugEvaluation

CDER评审官指南《色谱分析方法的验证》第1页共20页CenterforDrugEvaluationandResearch(CDER)ReviewerGuidanceValidationofChromatographicMethodsNovember1994CMC3TABLEOFCONTENTSCDER评审官指南《色谱分析方法的验证》第2页共20页I.INTRODUCTION目录.........................................................1II.TYPESOFCHROMATOGRAPHY绪言……...........................................2A.色谱分类HighPerformanceLiquidChromatography(HPLC)高效液相色谱1.ChiralChromatography手性液相色谱2.Ion-exchangeChromatography离子交换色谱......................................33.Ion-pair/AffinityChromatography离子对/亲和色谱...................................34.NormalPhaseChromatography正相色谱........................................35.ReversedPhaseChromatography反相色谱........................................36.SizeExclusionChromatography分子排阻色谱……..................................4B.GasChromatography(GC)气相色谱.......................………………………..4C.Thin-LayerChromatography(TLC)薄层色谱...............…………………….....5III.REFERENCESTANDARDS参考标准............................…………….....5IV.PARAMETERSFORVALIDATIONOFHPLCHROMATOGRAPHICMETHODSFORDRUGSUBSTANCEANDDRUGPRODUCT药物及其制剂HPLC方法验证的参数………………….....7A.Accuracy准确性………...............................……………………….........8B.DetectionLimitandQuantitationLimit检出限和定量限.....………………………........8C.Linearity线性…….........................................………………………..11D.Precision精密度.........................................……………………….131.Repeatability重复性...................................……………………………13a.InjectionRepeatability进样重复性...................…………………………………….13b.AnalysisRepeatability分析重复性...................…………………………………….152.IntermediatePrecision组间精密度.......................……………………………..153.Reproducibility重现性................................………………………………16E.Range范围……............................................……………………..16F.Recovery回收率............................................……………………..16G.Robustness耐久性..........................................…………………….16H.SampleSolutionStability供试品溶液的稳定性.....................……………………...17I.Specificity/selectivity专属性/选择性............................………………………17J.SystemSuitabilitySpecificationsandTests系统适用性规定和试验....…….………………211.Capacityfactor容量因子...............................……………………………...222.Precision/Injectionrepeatability精密度/进样重复性...........…………………………….223.Relativeretention相对保留时间............................…………………………….224.Resolution分离度…….................................………………………………225.Tailingfactor拖尾因子...................................…………………………….236.Theoreticalplatenumber理论塔板数...................…..…………………………..26K.GeneralPointstoConsider要点...............................…………………….28V.COMMENTSANDCONCLUSIONS注解和结论.........................……………..29VI.ACKNOWLEDGEMENTS致谢.................................…..…………….29VII.REFERENCES参考文献..........................................…………….291ThisguidancehasbeenpreparedbytheAnalyticalMethodsTechnicalCommitteeoftheChemistryManufacturingControlsCoordinatingCommittee(CMCCC)oftheCenterforDrugEvaluationandResearchattheFoodandDrugAdministration.AlthoughthisguidancedoesnotcreateorconferanyrightsfororonanypersonanddoesnotoperatetobindFDAortheindustry,itdoesrepresenttheagency’scurrentthinkingonthevalidationofchromatographicmethods.Foradditionalcopiesofthisguidance,contacttheDivisionofCommunicationsManagement,HFD-210,CDER,FDA,5600FishersLane,Rockville,MD20857(Phone:[phone]).SendoneCDER评审官指南《色谱分析方法的验证》第3页共20页self-addressedadhesivelabeltoassisttheofficesinprocessingyourrequest.AnelectronicversionofthisguidanceisalsoavailableviaInternettheWorldWideWeb()(connecttotheFDAHomePageat“RegulatoryGuidance”section).REVIEWERGUIDANCE1VALIDATIONOFCHROMATOGRAPHICMETHODSI.INTRODUCTIONThepurposeofthistechnicalreviewguideistopresenttheissuestoconsiderwhenevaluatingchromatographictestmethodsfromaregulatoryperspective.ThedocumentdiscussesthepointstonoteandweaknessesofchromatographysothatCDERreviewerscanensurethatthemethod'sperformanceclaimsareproperlyevaluated,andthatsufficientinformationisavailableforthefieldchemisttoassessthemethod.Analyticalterms,asdefinedbytheInternationalConferenceofHarmonization(ICH),1993,havebeenincorporatedinthisguide.本技术指南的目的是给审评人员审评验证色谱方法的,该文件讨论色谱方法的要点和不足,以便CDER的审评人员能够保证方法的良好性能，也使化学工作者了解为通过审评应给出的足够的信息。国际协调会议（ICH）1993年定义的分析术语，已在这一指南中运用。Chromatographicmethodsarecommonlyusedforthequantitativeandqualitativeanalysisofrawmaterials,drugsubstances,drugproductsandcompoundsinbiologicalfluids.Thecomponentsmonitoredincludechiralorachiraldrug,processimpurities,residualsolvents,excipientssuchaspreservatives,degradationproducts,extractablesandleachablesfromcontainerandclosureormanufacturingprocess,pesticideindrugproductfromplantorigin,andmetabolites.色谱方法通常用于原料、药物、药物制剂和生物体液中化合物的定性和定量。涉及的成分包括手性的或非手性的药物、过程杂质、残留溶媒、附加剂如防腐剂、分解产物、从容器和密闭包装或制造过程中带入的可提取和可过滤的杂质、植物药中的农药和代谢物等。Theobjectiveofatestmethodistogeneratereliableandaccuratedataregardlessofwhetheritisforacceptance,release,stabilityorpharmacokineticsstudy.Dataaregeneratedforthequalitativeandquantitativetestingduringdevelopmentandpostapprovalofthedrugproducts.Thetestingincludestheacceptanceofrawmate