溶出度方法学验证-8.ppt

ValidationTheanalyticalmethod1

USP1092

Thedissolutionprocedure:

DevelopmentandValidation Generalcomments“Thedissolutionprocedurerequiresanapparatus,adissolutionmediumandtestconditionsthatprovideamethodthatisdiscriminatingyetsufficientlyruggedandreproduciblefordaytodayoperationandcapableofbeingtransferredbetweenlaboratories”2

ChoiceoftheanalyticalmethodUVisalwayspreferredoverHPLCRememberyoumayuseaUVcellwithgreaterthan1cmpathlengthUVisunlikelytobesuitablewhen:-ThecompoundhasnoorlowwavelengthmaximaThedrugcontainsmorethanoneactiveTheconcentrationisverylow[1mgorless]Themediainterferes3

DissolutionmediainterferenceUVHPLCWATERNointerferenceNointerferencePHOSPHATEBUFFERSNointerferenceNointerferenceACETATEBUFFERSSignificantcutoffbelow240nmNomajorproblemTWEENSInterferenceatlowwavelengthInterfereswithcolumnathighconcentrationSLSSignificantinterferenceatlowλInterfereswithcolumnandsometimesincompatiblewithmobilephase4

ValidationoftheanalyticalmethodPlaceboeffectisallowed[upto2%USP]NoimpuritiesneedtobeconsideredAnyimpurities1%arebelowtheaccuracyofthedissolutiontestitselfHoweverthestabilityoftheactiveitselfmustbedemonstratedTheanalyticalmethodhastobevalidatedfor5

AnalyticalvalidationICHQ2(R1)

DissolutionAssayProcedurePARAMETEREARLYDEVELOPMENTFINALPROCEDUREACCURACYWhatisthis?YESPRECISIONRepeatabilityInterimprecisionReproducibilityYesNoNoYesYesYesSPECIFICITYYESYESLINEARITYRiskanalysisYESRANGERiskanalysisYESLODNONOLOQNONOROBUSTNESSSolutionstabilityYES3.ACCURACYTheaccuracyofananalyticalprocedureexpressestheclosenessofagreementbetweenthevaluewhichisacceptedeitherasaconventionaltruevalueoranacceptedreferencevalueandthevaluefound.Thisissometimestermedtrueness.6

LinearityandRangeThefollowingminimumspecifiedrangesshouldbeconsideredFortheassayofa