多肽类药物质量控制研究进展

*2011ZX09303－001＊＊[e-mail]*＊＊1000502226。HPLC、CELC－MS。。。Ｒ917A0254－1793201307－1115－06Ｒesearchprogressofthequalitycontrolofpeptidedrugs*TIANWen－jingＲENXueLIAOHai－mingYANGHua－xin＊＊NationalInstitutesforFoodandDrugControlBeijing100050ChinaAbstractInrecentyearspolypeptidesstudyhasbecomeaboomingtrendinnewdrugdevelopment．Thereare22monographsforAPIsand26forpreparations．TheimpurityinthesedrugswereusuallymeasuredbyHPLCCEandLC－MS．Thepresentstudycollectedandreviewedrelevantliteraturesthequalitycontrolespeciallyimpuritycon-trolwassummarized．Thecurrentsituationofqualitycontrolofpeptidedrugsandtheresearchprogresswerede-scribedwhichprovicesareferenceforthequalitycontrolofpeptidedrugs．Keywordspeptidedrugsqualitycontrolpharmacopoeiaimpuritydetectionmethod1953。。6030500～6001“”。。12－7、、、8。、、、、、、9。3、。。。12。2522ChP2010USP34JP166EP7.011。526ChP20108USP3413BP201211JP161。33—5111—ChinJPharmAnal20133371Tab1PeptidedrugsinpharmacopoeiaofvariouscountriesNo．drugnameChP2010USP34Ph．Eur7.0BP2012JP161calcitoninsalmon√√√√2elcatonin√3desmopressin√√4desmopressinacetate√5gonadorelinacetate√√√√6glutathione√7gonadorelinhydrochloride√8leuprolide√√9leuprolideacetate√10oxytocin√√√√11vasopressin√12alarelinacetate√13pentagastrin√√14somatostatin√√√15octreotideacetate√16thymalfasin√17buserelin√√18felypressin√√19goserelin√√20tetracosactide√√21protirelintartratehydrate√22protirelin√√2Tab2PeptidepreparationsinpharmacopoeiaofvariouscountriesNo．drugnameChP2010USP34BP2012JP161calcitoninsalmoninjection√√√2calcitoninsalmonnasalsolution√3corticotropininjection√4corticotropinforinjection√5corticotropinZincHydroxideInjectablesuspension√6desmopressininjection√√7desmopressintablets√8desmopressinIntranasalsolution√9desmopressinnasalspraysolution√10glucagonforinjection√11gonadorelinforinjection√12leuprolideinjection√13lypressinnasalsolution√14ergometrineandoxytocininjection√15oxytocininjection√√√√16oxytocinnasalsolution√17vasopressininjection√18alarelinacetateforinjection√19pentagastrininjection√√20somatostatinforinjection√21octreotideacetateinjection√22octreotideacetateforinjection√23thymalfasinforinjection√24goserelinimplants√25tetracosactideinjection√26tetracosactidezincinjection√—6111—ChinJPharmAnal2013337627ChP2010、、、、、、、、、、、、、、、、、、、、、、、、、。、、、、。、———。2、、。2.1。、、、、、、、、、10、、、、、、。、、11。、、USP34MSUSP342EP7.03、1HNMＲ、13C－NMＲ、。IＲ、NMＲ、MS。NMＲLC－MSLC－MS12。。210nm220nm。、93.9%±2.3%103.6%±1.3%。2.2、、。、、、、、。。。13HPLC。GuoAi1445℃、50℃55℃50℃30h37℃30d。—7111—ChinJPharmAnal20133373。12β－34。。。15。EP7.0“Substancesforpharmaceuti-caluse”160.1%0.5%1.0%。。。3.13.1.1、、。EP7.0USP34。。USP34EP7.0。3.1.2。USP、BP、ChP、、、USP、BPUlrikeHolzgrabeEP、JP、USP17EP7.0。Ｒidge18pHHPLC1。Catai19hGHhGH18Gln。CE。3.1.3MS。“”HPLC－ESI－MS/MS。。20。21ＲP－HPLCESI/MSMS/MS—8111—ChinJPharmAnal2013337。22。LC－ESI/QTOF－MSSystemin23。V．Sanz－NebotLC－ESI/MS24。Angelina2541CE－MSLC－MStBoctBu。3.1.4、。、。β26－275。Ph．Eur7.0CD。3.228。、。“”、“”“”、。21“”“”。。2010。。。。。29ＲP－HPLCMS。、。Goodlett30HPLC－MSGC－MSDL。—9111—ChinJPharmAnal2013337。1SHAJiang．IndustryStudy·Medicine·．BroadprospectsforpeptidedrugsEB/OL．2011.03.31．http//．doc88．com/p－0058743698171．html2USP34－NF29.20113BP．20104CHENWei－zhenYANGLa－hu．OutlineforBritishPharmacopoeia20122012．ChinJPharmAnal201232611105ChP．2010．VolⅡ531668411103111311336JP16.20107EP7.0.20118YANGHua－xinZHANGHuiDINGLi－xia．Theresearchstatusandprospectofhormonedrugs．ChinaPharm20081132879CHENGuang－hongCHIJian－guoQIUWeietal．ASurveyofpeptidedrugs．ShandongSci20082134210Technicalguidelinesfortheestablishmentofchemicaldrugqualitystandards．HGPH1－1.200511Technicalguidelinesforsyntheticpeptidedrugspharmacyresearch．HGPH11－1.200712VergoteVBurvenichCVandeWieleCetal．Qualityspecificationsforpeptidedrugsaregulatory－pharmaceuticalapproach．JPeptSci2009151169713LONGLeiWANGＲen－youTANGXiang－mingetal．Preparationandqualitycontroloftriptorelinacetatemicrosphere．JHubeiUnivNationMedEd20112821114AIGuoMEIXing－guo．Anacceleratedmethodtoevaluatethymopentinreleasefrommicrospheresinvitro．ChinPharm20081714115GomesIGrushkoJSGolebieUetal．Novelendogenouspeptideag-onistsofcannabinoidreceptors．FASEBJ200923116EP7.0.SubstancesforPharmaceuticaluse．2009/0117UlrikeH．TheneedforCEmethodsinpharmacopoeialmonographs．SeparSciTechnol2008924518ShaneＲKanthiH．Peptidepurityandcounteriondeterminationofbradykininbyhigh－performanceliquidchromatographyandcapil-laryelectrophoresis．JChromatogrA199881721519CataiJToranoJJongenPetal．Analysisofrecombinationhumangrowthhormonebycapillaryelectrophoresiswithbilayer－coatedcapillariesusingUVandMSdetection．JChromatogrB20078521－216020GAOMingYANXiao－danJINSongetal．Applicationofliquidchromatography－massspectrometryindrugrelatedsubstancesanalysisLC－MS．DrugEvalＲes20123516321TANGXin－keWANGXian－chunLIANGSong－ping．Analysisofcrudesyntheticproductofatride-capeptidebyＲP－HPLC/ESI－MSandMS/MS．JNatSciHunanNormUniv20042737522LIPingWANGHong－xiaWANGHong－lietal．Analysisoftheprimarystructureofmodifiedandun-knownpeptidesbynanoelectrospraytandemmassspectrometry．JInstrumA-nal20072681223DUFu－youBAIYuLIUHu－wei．Massspectrometricfragmentationmechanismandchromatographic