3296-3297 Gabapentin加巴喷丁美国药典标准

3296Gabapentin/OfficialMonographsUSP35GabapentinRS,USPGabapentinRelatedCompoundARS,and.USPGabapentinRelatedCompoundBRS,respectively.GabapentinTestsolution—UsetheAssaypreparation.Standardsolution—DissolveasuitablequantityofUSPGabapentinRelatedCompoundERSinDiluenttoobtainasolu-tionhavingaknownconcentrationof8.4μgpermL.Chromatographicsystem(seeChromatography〈621〉)—Pre-C9H17NO2171.24pareasdirectedintheAssay.ChromatographtheSystemsuita-Cyclohexaneaceticacid,1-(aminomethyl)-.bilitysolution(about20μL),andrecordthepeakresponsesas1-(Aminomethyl)cyclohexaneaceticacid[60142-96-3].directedforProcedure:identifythemajorpeaksusingtherela-tiveretentiontimesgiveninTable1:theresolution,R,between»Gabapentincontainsnotlessthan98.0percentgabapentinrelatedcompoundAandgabapentinrelatedcom-andnotmorethan102.0percentofC9H17NO2,poundBisnotlessthan2.3;andtherelativestandarddevia-calculatedontheanhydrousbasis.tionforgabapentinisnotmorethan2.0%.Procedure—Separatelyinjectequalvolumes(about20μL)ofPackagingandstorage—Preserveinwell-closedcontainers.theStandardsolutionandtheTestsolutionintothechromato-Storeatroomtemperature.graph,recordthechromatograms,andmeasurethepeakre-sponses.Calculatethepercentageofanyimpurityinthepor-USPReferencestandards〈11〉—tionofGabapentintakenbytheformula:USPGabapentinRSUSPGabapentinRelatedCompoundARS100(1/F)CS/CT)(ri/rS)2-Aza-spiro[4.5]decan-3-one.C9H15NO153.22inwhichFistherelativeresponsefactoroftheimpurity(rela-USPGabapentinRelatedCompoundBRStivetogabapentinrelatedcompoundE)accordingtoTable1;(1-Cyano-cyclohexyl)-aceticacid.CSistheconcentration,inmgpermL,ofUSPGabapentinRe-C9H13NO2167.21latedCompoundERSintheStandardsolution;CTistheconcen-USPGabapentinRelatedCompoundDRStrationofGabapentin,inmgpermL,intheTestsolution;riis(1-(3-Oxo-2-aza-spiro[4.5]dec-2-ylmethyl)-cyclohexyl)-aceticthepeakareaforanyimpurityintheTestsolution;andrSistheacid.peakareaforgabapentinrelatedcompoundEintheStandardC18H29NO3307.43solution:theimpuritiesmeettherequirementsgiveninTable1.USPGabapentinRelatedCompoundERSCarboxymethyl-cyclohexanecarboxylicacid.LIMITOFLATEELUTINGIMPURITIES—C9H14O4186.21Diluent—Dissolve2.32gofammoniumphosphatemonoba-Identification—sicin1000mLofwater.AdjustwithphosphoricacidtoapHof2.0.A:InfraredAbsorption〈197K〉.Buffersolution—ProceedasdirectedintheAssay.B:Theretentiontimeofthemajorpeakinthechromato-gramoftheAssaypreparationcorrespondstothatinthechro-Mobilephase—PrepareafilteredanddegassedmixtureofmatogramoftheStandardpreparation,asobtainedintheAssay.Buffersolution,acetonitrile,andmethanol(35:35:30).Makead-justmentsifnecessary(seeSystemSuitabilityunderChromatogra-pH〈791〉:between6.5and8.0,inasolution(1in50).phy〈621〉).Water,MethodI〈921〉:notmorethan0.5%.Standardsolution—DissolveanaccuratelyweighedquantityResidueonignition〈281〉:notmorethan0.1%.ofUSPGabapentinRelatedCompoundDRSinasmallamountHeavymetals,MethodII〈231〉:0.002%.ofmethanol,anddilutequantitatively,andstepwiseifneces-Relatedcompounds—sary,withDiluenttoobtainasolutionhavingaknownconcen-trationofabout0.0028mgpermL.LIMITOFEARLYELUTINGIMPURITIES—Testsolution—UsetheAssaypreparation.Diluent,Buffersolution,Mobilephase,andChromatographicsystem—ProceedasdirectedintheAssay.Chromatographicsystem(seeChromatography〈621〉)—Theliquidchromatographisequippedwitha215-nmdetectorandImpuritiessolution—DissolvesuitablequantitiesofUSPa4.6-mm×25-cmcolumnthatcontainspackingL1.TheflowGabapentinRelatedCompoundARSandUSPGabapentinRe-rateisabout1mLperminute.ThecolumntemperatureislatedCompoundBRSinmethanoltoobtainasolutioncontain-maintainedat40°.ChromatographtheStandardsolution,andingabout1.4mgpermLand0.84mgpermL,respectively.recordthepeakresponsesasdirectedforProcedure:thecolumnSystemsuitabilitysolution—DissolveasuitablequantityofUSPefficiencyisnotlessthan13,600theoreticalplatesfortheGabapentinRSinDiluent,andaddanappropriatevolumeofgabapentinrelatedcompoundDpeak;andtherelativestan-Impuritiessolutiontoobtainasolutioncontainingabout14.0darddeviationforreplicateinjectionsisnotmorethan7.0%.mgpermL,0.014mgpermL,and0.0084mgpermLofUSPTable1RelativeRetentionTime1CompoundName(approximate)RelativeResponseFactor2Limit(%)GabapentinrelatedcompoundE2.91.00.10GabapentinrelatedcompoundA3.55.30.1GabapentinrelatedcompoundB3.80.350.06Individualunknownimpurity—0.410.101Therelativeretentiontimesarecalculatedbasedontheretentiontimeofgabapentin.[NOTE—Thisinformationisforidentificationpurposesonly.]2TherelativeresponsefactorsarecalculatedbasedontheresponseofgabapentinrelatedcompoundEduetothelowabsorptivityofgabapentinatthemonitoringwavelength(215nm).OfficialfromMay1,2012Copyright(c)2011TheUnitedStatesPharmacopeialConvention.Allrightsreserved.Accessedfrom128.83.63.20bynEwp0rt1onThuNov2404:17:00EST2011USP35OfficialMonographs/Gabapentin3297Procedure—Separatelyinjectequalvolumes(about20μL)of.theStandardsolutionandtheTestsolutionintothechromato-GabapentinCapsulesgraph,recordthechromatograms,andmeasuretheresponsesforthemajorpeaks.[NOTE—Disregardallthepeakshavingrela-»GabapentinCapsulescontainnotlessthantiveretentiontimesof0.35