《Metabolism of Mequindox in Isolated Rat Liver Cells.》.pdf

Availableonlineatwww．sciencedirect．corn Metabolism ofMequindoxinIsolatedRatLiverCells LIGuang—hui，，SHANQi，WANGJing，LIYa—fei，GAOYanandZENGZhen—ling NationalReferenceLaboratoryofVeterinaryDrugResidues(SCAU)，CollegeofVeterinaryMedicine,SouthChinaAgriculturalUniversity Guangzhou510642，P．R．China 。JieYangEntry—ExitInspectionandQuarantineBureau，Jieyang522031P．R．China Abstract Mequindox(MEQ)，3-methyl一2-quinoxahnacetyl-l，4-dioxide，iswidelyusedinChineseveterinarymedicineasan antimicrobialagentandfeedadditive．Itstoxicityhasbeenreportedtobecloselyrelatedtoitsmetabolism．Tounderstand thepathwaysunderlyingMEQ’smetabolism moreclearly，westudieditsmetabolism inisolatedratlivercellsbyusing liquidchromatographycoupledwithelectrosprayionizationhybridlineartrapquadrupoleorbitrap(LC-LTQ—Orbitrap)mass spectrometry．ThestructuresofMEQmetabolitesandtheirproductionswerereadilyandreliablycharacterizedonthebasis ofaccurateMS spectraandknownstructureofMEQ．Elevenmetabolitesweredetectedinisolatedratlivercells．twoof whichweredetectedforthefirsttimeinvitro．Themajormetabolicpathwaysreportedpreviouslyofrinvitrometabolism ofMEQinratmicrosomeswereconfirmedinthissutdy，includingN—Ogroupreduction，carbonylreduction，andmethy1 monohydroxylation．Inaddition，wefoundthatacetylhydroxylationwasanimportantpathwayofMEQmetabolism．The resultsalsodemonstratethatcellularsystemsmorecloselysimulateinvivoconditionsthandootherinvitrosystemssuchas microsomes．Takentogether．thesedatacontributetoourunderstandingofthefvivometabolismofMEQ． Keywords：mequindox，isolatedratlivercells，metabolism，metabolites，LC-LTQ—Orbitrap severalrecentinvivoandinvitrostudieshaverevealed lNTRODUCTlON potentialadrenal(Huangeta1．2009)，endocrine， reproductive(Ihsaneta1．2011)，andkidneytoxicities