血浆中决奈达隆和活性代谢产物sr35021的定量分析方法的的研究与其应用

《血浆中决奈达隆和活性代谢产物sr35021的定量分析方法的的研究与其应用》由会员上传分享，免费在线阅读，更多相关内容在学术论文-天天文库。

1、和4．5h，血浆消除半衰期分别约为16h和22h。活性代谢物SR35021在人体内的血浆暴露量明显高于在比格犬体内，其在人血浆中的暴露量略高于原形药物。结论：建立了快速、灵敏的LC-MS／MS法同时测定决奈达隆和活性代谢产物SR35021血浆浓度，并成功应用于盐酸决奈达隆片药动学研究。关键词：决奈达隆代谢物SR35021药代动力学LC-MS／MS2QuantitativeanalysesofdronedaroneanditsactivemetaboliteSR35021inplasmaandapplicationsMasterdegreecandidate：YangShilei

2、Supervisor：ProfessorTangXinqiangMajor：PharmacologyAbstractObjective：Todevelopandvalidatealiquidchromatography-tandemmassspectrometry(LC--l订S／MS)methodforthesimultaneousdeterminationofdronedaroneanditsmetaboliteSR35021inplasmatostudytherelativebioavailabilityandpharmacokineticinBeagledogandhe

3、althhuman．Methods：FordeterminationofthedogplasmaconcentrationofdronedaroneanditsmetaboliteSR35021，analiquotof50pLplasmaWastreatedbyproteinprecipitationwithacetonitrile，dronedarone，SR35021andinternalstandard(tolvaptan)wereseparatedonaCapcellPakClsMGcolumnusingacetonitrile-methanol-5mmol／Lammo

4、niumacetate-aceticacid(55：10：35：O．07，V／、，^，^，)asthemobilephase．FordeterminationofthehumanplasmaconcentrationofdronedaroneandSR35021，an‘aliquotof50laLplasmaWastreatedbyproteinprecipitation、)l，imacetonitrile，dronedarone，SR35021andinternalstandard(amiodarone)wereseparatedonaCapcellPakClsMGcolum

5、nusingacetonitrile-5mmol／Lammoniumacetate—aceticacid弱mobilephasebygradientelution．Atandemmassspectrometerequippedwi廿latmosphericpressurechemicalionizationsourcewasusedasdetectorandoperatedinthepositiveionmode．Quantificationwasperformedusingmultiplereactionmonitoring(MRM)ofthetransitionsm／z55

6、7专m／z100，m／z501专m／zl14，m／z449一m／z252andm／z646---．ym／z100fordronedarone，SR35021，IS(tolvaptan)andIS(amiodarone)，respectively．Results：ThelinearrangesofthecalibrationcurvesfordronedaroneandSR35021werebotll0．200～200ng／mL．Thelowerlimitofquantitation(LLOQ)ofdronedaroneandSR35021wereboth0．200ng／mL．T

7、heinwa-dayandinter-dayprecisionfRSD)ofdronedaroneandSR35021werebothlessthan15％．Theaccuracy承E)Waswithin-15～15％．After趾oraladministrationofdronedaronehydrochloridetablet(400mg)3(ReferenceandTest)toBeagledogs，themean％觚valuesofdronedaroneandSR35021wereb