Isolation and characterization of a degradation product in leflunomide and a validated selective stability-indicating HPLC-UV method for their quantification.pdfVIP

JournalofPharmaceuticalAnalysis20l5；5(3)：207—212 Contentstistsavaltabteat~ enceDirect JournalofPharmaceuficfl Analysis www．elseviercom／locate／jpa www．sciencedirecLcom SH0RT COMM UNICAT10N 蠹一 —lsollaUJ■on anc1IcIliarac riz‘atio‘n oI■a d一e~rad一ati‘o‘n CrossMark productinleflunom ideandavalidated selective stability——indicatingHPLC-UV methodfor theirquantification BalrajSaini，GulshanBansal术 DepartmentofPharmaceuticalSciencesandDrugResearch，PunjabiUniversity,Patiala147002，India Received 14May2014；revised26September2014；accepted 10October2014 Avai1ableonline22October2014 Abstract Leflunomide (LLM)issubjectedtoforceddegradationunderconditionsofhydrolysis， oxidation，dry heat，andphotolysisasrecommendedbyIntemationalConferenceon Harmonization Leflunomide； guidelineQ1A(R2)．Intotal，fourdegradationproducts(I_Ⅳ)wereformedunderdifferentconditions． Characterization； Forceddegradation； Products I．IInad IV werefomr ed in alkalinehydrolytic，acidichydrolyticnad alkalinephotolytic Degradationproduct； conditions．LLM na dalldegradationproductswereoptimallyresolvedby gradientelutionoveraC1R 唧 C-IⅣ column．ThemaiordegradationproductfIV)fomred inhydrolyticalkalineconditionswasisolated throughcolumnchromatography．BasedonitsHNM R，IR andmassspectraldata，itwascharacterizedas aBritishPharmacopoeialimpufity B．TheHPLC method wasfound tobe linear．accurate．precise． sensitive．specific，ruggedandrobustforquna tificationofLLM aswellasproduct