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超高效液相色谱-串联质谱法测定犬血浆中利培酮和帕潘立酮及药代动力学研究.docx

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超高效液相色谱-串联质谱法测定犬血浆中利培酮和帕潘立酮及药代动力学研究 Title:DeterminationofLurasidoneandPaliperidoneinCaninePlasmausingUltra-HighPerformanceLiquidChromatography-TandemMassSpectrometryandPharmacokineticStudy Abstract: LurasidoneandPaliperidonearewidelyusedantipsychoticdrugsforthetreatmentofvariouspsychiatricdisordersinbothhumanandveterinarymedicine.Inthisstudy,wedevelopedandvalidatedanultra-highperformanceliquidchromatography-tandemmassspectrometry(UHPLC-MS/MS)methodforthedeterminationofLurasidoneandPaliperidoneincanineplasma.Themethodwassuccessfullyappliedtoinvestigatethepharmacokineticsofthesedrugsindogsafteroraladministration. Introduction: LurasidoneandPaliperidonearesecond-generationantipsychoticswithpotentserotoninanddopaminereceptorantagonism.Theyarecommonlyprescribedforthetreatmentofschizophrenia,bipolardisorder,andotherpsychiatricconditionsinhumans.Duetosimilaritiesintheneurophysiologyandpathophysiologyofhumanandcaninepsychiatricdisorders,thesedrugsarealsousedoff-labelforthetreatmentofbehavioraldisordersindogs.Therefore,itisimportanttodevelopapreciseandsensitiveanalyticalmethodtodeterminetheconcentrationsofLurasidoneandPaliperidoneincanineplasma,enablingpharmacokineticstudiesindogs. Experimental: SamplePreparation: CanineplasmasampleswereobtainedfromdogsreceivingoraldosesofLurasidoneorPaliperidone.Plasmasamplesweredeproteinizedusingacetonitrileandthesupernatantwascollectedaftercentrifugation.ThesupernatantwasevaporatedandreconstitutedwiththemobilephaseforUHPLC-MS/MSanalysis. UHPLC-MS/MSAnalysis: TheUHPLC-MS/MSsystemconsistedofabinarysolventdeliverysystem,anautosampler,acolumnoven,andatriplequadrupolemassspectrometerequippedwithanelectrosprayionizationsource.ChromatographicseparationwasperformedonaC18columnwithamobilephaseconsistingofamixtureofacetonitrileandwaterwith0.1%formicacid.Massspectrometricdetectionwascarriedoutusingmultiplereactionmonitoring(MRM)modewithspecifictransitionsforLurasidone,Paliperidone,andtheirinternalstandards. MethodValidation: Themethodwasvalidatedfol