盐酸二甲双胍质量标准(英国药典)

MetforminHydrochlorideC4H11N5·HCl165.62Imidodicarbonimidicdiamide,N,N-dimethyl-,monohydrochloride.1,1-Dimethylbiguanidemonohydrochloride[1115-70-4].»MetforminHydrochloridecontainsnotlessthan98.5percentandnotmorethan101.0percentofC4H11N5·HCl,calculatedonthedriedbasis.USPReferencestandards11—USPMetforminHydrochlorideRS.USPMetforminRelatedCompoundARS.Identification—A:InfraredAbsorption197K.B:ItmeetstherequirementsofthetestsforChloride191.Lossondrying731—Dryitat105for5hours:itlosesnotmorethan0.5%ofitsweight.Residueonignition281:notmorethan0.1%.Heavymetals,MethodI231:0.001%.Relatedcompounds—Mobilephase—Prepareasolutioninwater,containing17gofmonobasicammoniumphosphateperL,adjustwithphosphoricacidtoapHof3.0,andmix.Standardsolution—PrepareasolutionofUSPMetforminRelatedCompoundARSinwaterhavingaknownconcentrationofabout0.2mgpermL.Transfer1.0mLofthissolutiontoa200-mLvolumetricflask,dilutewithMobilephasetovolume,andmix.[NOTE—MetforminrelatedcompoundAis1-cyanoguanidine.]Testsolution—Transferabout500mgofMetforminHydrochloride,accuratelyweighed,toa100-mLvolumetricflask,dissolveinanddilutewithMobilephasetovolume,andmix.Dilutedtestsolution—Transfer1.0mLoftheTestsolutiontoa10-mLvolumetricflask,dilutewithMobilephasetovolume,andmix.Transfer1.0mLofthissolutiontoa100-mLvolumetricflask,dilutewithMobilephasetovolume,andmix.Resolutionsolution—Transferabout10mgofmelaminetoa100-mLvolumetricflask,anddissolveinabout90mLofwater.Add5.0mLoftheTestsolution,dilutewithwatertovolume,andmix.Transfer1.0mLofthissolutiontoa50-mLvolumetricflask,dilutewithMobilephasetovolume,andmix.Chromatographicsystem(seeChromatography621)—Theliquidchromatographisequippedwitha218-nmdetectoranda4.6-mm×25-cmcolumncontainingpackingL9.Theflowrateisabout1.0to1.7mLperminute.ChromatographtheResolutionsolution,andrecordthepeakresponsesasdirectedforProcedure:theresolution,R,betweenmelamineandmetforminisnotlessthan10.Procedure—Separatelyinjectequalvolumes(about20µL)oftheTestsolution,theStandardsolution,andtheDilutedtestsolutionintothechromatograph,recordthechromatogramsfornotlessthantwicetheretentiontimeofmetformin,andmeasurethepeakareas.TheareaofapeakcorrespondingtometforminrelatedcompoundAinthechromatogramoftheTestsolutionisnotgreaterthantheareaofthecorrespondingpeakinthechromatogramoftheStandardsolution:notmorethan0.02%ofmetforminrelatedcompoundAisfound.TheareaofanyothersecondarypeakinthechromatogramoftheTestsolutionisnotgreaterthantheareaofthemajorpeakinthechromatogramoftheDilutedtestsolution;andthesumoftheareasofallsecondarypeaksinthechromatogramoftheTestsolutionisnotgreaterthanfivetimestheareaofthemajorpeakinthechromatogramoftheDilutedtestsolution:notmorethan0.1%ofanyotherimpurityisfound;andnotmorethan0.5%oftotalimpuritiesisfound.Assay—[NOTE—Toavoidoverheatingofthereactionmedium,mixthoroughlythroughoutthetitration,andstopthetitrationimmediatelyaftertheendpointhasbeenreached.]Dissolveabout60mgofMetforminHydrochloride,accuratelyweighed,in4mLofanhydrousformicacid.Add50mLofaceticanhydride.Titratewith0.1NperchloricacidVS,determiningtheendpointpotentiometrically.Performablankdetermination,andmakeanynecessarycorrection(seeTitrimetry541).EachmLof0.1Nperchloricacidisequivalentto8.28mgofC4H11N5·HCl.USP28AuxiliaryInformation—StaffLiaison:ElenaGonikberg,Ph.D.,ScientistExpertCommittee:(PA4)PharmaceuticalAnalysis4USP28–NF23Page1231PharmacopeialForum:VolumeNo.29(6)Page1925PhoneNumber:1-301-816-8251MetforminHydrochloride(PhEurmonograph0931)C4H11N5,HCl165.61115-70-4PhEurDEFINITION1,1-Dimethylbiguanidehydrochloride.Content98.5percentto101.0percent(driedsubstance).CHARACTERSAppearanceWhitecrystals.SolubilityFreelysolubleinwater,slightlysolubleinalcohol,practicallyinsolubleinacetoneandinmethylenechloride.IDENTIFICATIONFirstidentificationB,E.SecondidentificationA,C,D,E.A.Meltingpoint(2.2.14):222Cto226C.B.Infraredabsorptionspectrophotometry(2.2.24).Preparation.DiscsofpotassiumchlorideR.Comparison:MetforminhydrochlorideCRS.C.Thin-layerchromatography(2.2.27).Testsolution.Dissolve20mgofthesubstancetobeexaminedinwaterRanddiluteto5mlwiththesamesolvent.Referencesolution.Dissolve20mgofmetforminhydrochlorideCRSinwaterRanddiluteto5mlwiththesamesolvent.Plate.TLCsilicagelGplateR.Mobilephase.Upperlayerofamixtureof10volumesofglacialaceticacidR,40volumesofbutanolRand50volumesofwaterR.Application.5µl.Development.Overapathof15cm.Drying.At100C105Cfor15min.Detection.Spraywithamixtureofequalvolumesofa100g/lsolutionofsodiumnitroprussideR,a100g/lsolutionofpotassiumferricyanideRanda100g/lsolutionofsodiumhydroxideR,prepared20minbeforeuse.Results.Theprincipalspotinthechromatogramobtainedwiththetestsolutionissimilarinposition,colourandsizetotheprincipalspotinthechromatogramobtainedwiththereferencesolution.D.Dissolveabout5mginwaterRanddiluteto100mlwiththesamesolvent.To2mlofthesolutionadd0.25mlofstrongsodiumhydroxidesolutionRand0.10mlofa-naphtholsolutionR.Mixandallowtostandinicedwaterfor15min.Add0.5mlofsodiumhypobromitesolutionRandmix.Apinkcolourdevelops.E.Itgivesreaction(a)ofchlorides(2.3.1).TESTSS