lcmsms法测定小鼠血浆和脑组织中ljp1207含量并应用于药代动力学分析-lcm sms method was used to determine ljjp 1207 content in mouse plasma and brain tissue and to analyze its pharmacokinetics..docxVIP

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2018-05-28 发布于上海
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lcmsms法测定小鼠血浆和脑组织中ljp1207含量并应用于药代动力学分析-lcm sms method was used to determine ljjp 1207 content in mouse plasma and brain tissue and to analyze its pharmacokinetics..docx

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lcmsms法测定小鼠血浆和脑组织中ljp1207含量并应用于药代动力学分析-lcm sms method was used to determine ljjp 1207 content in mouse plasma and brain tissue and to analyze its pharmacokinetics.

ABSTRACTThereissemicarbazide-sensitiveamineoxidases(SSAO)inbothplasmaandtissuesofmammal.IncreasesofSSAOleveloccursinmanyinflammatorydiseasesandcardiovascularandcerebrovasculardiseases.LJP1207[N’-(2-phenylallyl)hydrazineHydrochloride]isapotent,selectiveandorallyavailableinhibitortoSSAO,whichmakesLJP1207apotentialtherapeuticdruginacuteandchronicinflammation,furthermoer,vasculardementia.However,LJP1207isunstableinbiologicalsamples.Inthisstudy,asimpleandsensitiveLC-MS/MSmethodforthequantitativeofLJP1207inBALB/Cmouseplasmaandbraintissuehasbeendevelopedandvalidated.ThismethodwassuccessfullyappliedtopharmacokineticstudyofLJP1207.Proceduresandmethods:一、ThequantitativedeterminationofLJP1207inBALB/CmouseplasmaandbrainSamplescontainningLJP1207wereprocessedusingacetonitrileandthenaderivatizationwith2,4-pentanedioneat30℃for30min.Asolidphaseextractionwasfollowedtoremovetheimpurity.ChromatographicseparationwasperformedonaWatersSymmetryC18column(2.1×50mm,3.5μm)withamixedsolutionofmethanol-10mMaqueousammoniumacetate(pH5.0)(75:25,v/v)asmobilephase,andoperatedataflowrateof0.2mL/min.Quantificationwasperformedbythemultiplereactionmonitoring(MRM)ofthetransitionwithm/z213→117intheelectrospraypositiveionizationmode.二、PharmacokineticstudyofLJP1207inBALB/CmouseandSDratAfterasingleintraperitonealinjectionofLJP1207atthedoseof30mg/kgtoBALB/CmoseandSDrat,bloodandbrainsamplesofBALB/Cmousewerecollectedatcontrol(0min)、3、6、9、12、15、30、45、60、90and120min,whileplasmasamplesofSDratwerecollectedatcontrol(0min)、5、15、30、45、60、90、120、360and720min.Thewholebloodwascollectedandcentrifugedat1,600×gfor4min.Then50μLplasmawasmixedwith50μL2,4–pentanedione(5%,inwater).afterthat,theywerefrozenat-80℃foranalyzed.Wholebraintissueswerecollectedandforzenat-80℃immediately.Fordetermination,theplasmaandbrainsamplesfrozenwerefetchedoutandprocessedusingacetonitrileandthenaderivatizationwith2,4-pentanedioneat30℃for30min.Asolidphaseextractionwasfollowedtoremovetheimpurity.TheconcentrationofLJP1207ateachsamplewasdeterminedbytheabo