芍药苷在正常大鼠体内的多剂量药物动力学分析-multi - dose pharmacokinetic analysis of paeoniflorin in normal rats.docxVIP

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芍药苷在正常大鼠体内的多剂量药物动力学分析-multi - dose pharmacokinetic analysis of paeoniflorin in normal rats.docx

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芍药苷在正常大鼠体内的多剂量药物动力学分析-multi - dose pharmacokinetic analysis of paeoniflorin in normal rats

Studyofpharmacokineticsofmulti-doseofpaeoniflorininnormalratsPh.Mcandidate:BinLiuPreceptor:Prof.WeiWei(InstituteofClinicalPhamacology,AnhuiMedicalUniversity,KeyLaboratoryofAnti-inflammatoryandImmunophamacologyofEducationMinistry,KeyLaboratoryofResearchandDevelopmentofChineseMedicineinAnhuiProvince,AnhuiEngineeringTechnologyResearchCenterofAnti-inflammatoryandImmunodrugs,ScientificandTechnologicalInnovationTeamofAnti-inflammatoryandImmunopharmacologyforChineseMedicineinAnhuiProvince,the115industialinnovationteamofbasicandappliedresearchintoanti-inflammationandimmunodrugsinanhuiprovince,Hefei,230032)AbstractTotalglucosidesofpaeony(TGP),whichisusedtotreatrheumatoidarthritis(RA),ispresentedbynumbersofpharmacies,whosemaincomponentisPaeoniflorin(Pae),andbothdrugshaveagoodanti-inflammatoryandimmunomodulatoryeffect.ButtheeffectofTGPisveryslow,accordingtothereferencethatwhenPaewasgivenbyintragastric(ig)administrationtotheratsalone,thebioavailabilityofPaeisonly0.3%,soasthemaincomponentofTGP,thepoorabsorptionofPaemaybeoneofthereasonswhichresultinthesloweffect.Objective：Todeveloparapid.sensitiveandselectiveliquidchromatographytandemspectrometry(LC-MS)methodforthedeterminationofPaeinratbiologicalspecimen,andtoinvestigateitsmulti-dosepharmacokineticsparametersinrats.Methods：HPLCanalysiswascarriedoutonaC18column(250mm×2.0mm,3μm)withamobilephaseconsistingofmethanoland0.1%formicacid(70:30).Detectionwascarriedoutonatriplequadrupoletandemmassspectrometerbyselected-reactionmonitoringandanelectrosprayionizationsourcewasemployedastheionizationsource.ThePhamacokineticcharacteristicsofpaeoniflorinwasinvestigatedafteroraladminstrationtoratsinthreedosages.PharmacokineticparameterswerecalculatedwithDAS2.0practicalpharmacokineticsprogram..Results：LC-MSanalysisofPaeinbiologicalsamplesAsensitiveandspecificLC-MSmethodwasdevelopedforthesimultaneousofPaeandGinkgolideB（internalstandard）inbiologicalsamples.PaeandGinkgolideBwereisolatedfromthebiologicalsamplespriortoLC-MSanalysisusingliquid-liquidextr