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1、学报JournalofChinaPharmaceuticalUniversity2007,38(3):247-251247LC-MS/MS法同时测定人血浆中盐酸二甲双胍和罗格列酮浓度及其药代动力学111X2张璐,田媛,张尊建,陈(1中国药科大学分析测试中心,南京210009;2中国医学科学院皮肤病研究所,南京210042)摘要目的:建立LC-MS/MS同时测定人血浆中盐酸二甲双胍及罗格列酮浓度的方法,测定志愿者单次和多次顿服二甲双胍罗格列酮胶囊后盐酸二甲双胍和罗格列酮的血药浓度,估算其药代动力学参数。方法:血浆中加入盐酸苯乙双胍为内标,经乙腈沉淀蛋白
2、,取上清直接进行LC-MS/MS测定。色谱柱为PhenomenexLunaCN100A(150mm@210mmID),流动相为CH3OH-30mmol/LNH4Ac,pH510(80B20),流速为012mL/min;ESI-MS/MS选择性反应正离子检测。临床试验方案采用拉丁方试验设计。结果:盐酸二甲双胍和罗格列酮的血浆线性范围分别为5~3000ng/mL和115~500ng/mL,检测限均为1ng/mL。测定了12名志愿者单次和多次顿服二甲双胍罗格列酮胶囊后的血药浓度经时过程。结论:本方法操作简单,专属性强,灵敏度高,准确性好。盐酸二甲双胍和罗格
3、列酮体内动力学行为符合线性药物动力学特征。关键词盐酸二甲双胍;罗格列酮;高效液相色谱-串联质谱法;药代动力学中图分类号R969.1文献标识码A文章编号1000-5048(2007)03-0247-05SimultaneousdeterminationofmetforminandrosiglitazoneinhumanplasmabyLC-MS/MSandthepharmacokineticsstudies1112ZHANGLu,TIANYuan,ZHANGZun-jian,CHENYun1CenterforInstrumentalAnalysis,C
4、hinaPharmaceuticalUniversity,Nanjing210009;2InstituteofDermatology,ChineseAcademyofMedicalSciences&PerkingUnionMedicalCollege,Nanjing210042,ChinaAbstractAim:ToestablishanLC-MS/MSmethodtostudythepharmacokineticsofmetforminandrosiglitazoneinhumanplasma.Methods:Afteraddingphenform
5、in,theinternalstandard,plasmasampleswereprecipitatedbyacetonitrileandthesupernatantwasinjectedontoLC-MS/MSsystem.ThechromatographicsystemconsistedofPhenomenexLunaCN100Acolumn(150mm@210mmID)andthemobilephaseofCH3OH-NH4Ac(30mmol/L,pH510)(80B20)ataflowrateof012mL/min.Accordingtoth
6、ecrossoverdesignusinglatinsquare,12volunteersorallyreceivedtestcapsulesinsingleandmultiple-dosingandplasmaconcentrationsofmetforminandrosiglitazoneweredeterminedbythevalidatedmethod.Pharmacokineticparametersofthetwospecieswereestimated.Results:Themethodexhibitedlinearrangesoffr
7、om5to3000ng/mLand115to500ng/mLwithacorrelationcoefficientof019995and019992formetforminandrosiglitazone,respectively.Thelimitofdetectionwas1ng/mLforbothmetforminandrosiglitazone.Theconcentration-timecurvesofmetforminandrosiglitazonewerebestfittedtoatwo-compartmentopenmodel.Concl
8、usion:Themethodissimple,sensitiveandrapid.Theabsorptio
