Structuralconfirmationofsulconazolesulfoxideastheprimarydegradationproductofsulconazolenitrate

摘要： Sulconazolehasbeenreportedtodegradeintosulconazolesulfoxideviasulfuroxidation;however,structuralcharacterizationdatawaslackingandthepotentialformationofanN-oxideorsulfonecouldnotbeexcluded.ToclarifythedegradationpathwaysandincorporatetheimpurityprofileofsulconazoleintotheUnitedStatesPharmacopeia–NationalFormulary(USP–NF)monographs,amultifacetedapproachwasutilizedtoconfirmtheidentityofthedegradant.Theapproachcombinesstresstestingofsulconazolenitrate,chemicalsynthesisofthedegradantviaahydrogenperoxide-mediatedoxidationreaction,semi-preparativeHPLCpurification,andstructuralelucidationbyLC–MS/MSandNMRspectroscopy.Structuraldeterminationwasprimarilybasedonthecomparisonofspectroscopicdataofsulconazoleandtheoxidativedegradant.ThemassspectrometricdatahaverevealedaMcLafferty-typerearrangementasthecharacteristicfragmentationpathwayforalkylsulfoxideswithaβ-hydrogenatom,andwasusedtodistinguishthesulfoxidefromN-oxideorsulfonederivatives.Moreover,thegeneratedsulconazolesulfoxidewasutilizedasreferencematerialforcompendialproceduredevelopmentandvalidation,whichprovidessupportforUSPmonographmodernization. ... （共7页）