LC-MS/MS法测定人血浆中的安纳拉唑及药动学初步应用  

Determination of anaprazole in human plasma by LC-MS/MS in pharmacokinetic study

作　　者：程东霞[1,2] 戴晓健[2] 张逸凡[2] 吴永谦 石崇铁 马西凤 李晋 陈笑艳[2] 钟大放[1,2] 

机构地区：[1]浙江工业大学药学院,浙江杭州310014 [2]中国科学院上海药物研究所,上海201203 [3]山东轩竹医药科技有限公司,山东济南250100

出　　处：《药学学报》2016年第12期1885-1890,共6页Acta Pharmaceutica Sinica

基　　金：重大新药创制科技重大专项资助项目(2014ZX09304002-008-001);中国科学院上海药物研究所新药研究国家重点实验室项目(SIMM1501ZZ-02)

摘　　要：安纳拉唑是处于临床试验阶段的口服用质子泵抑制剂。本文建立了液相色谱-串联质谱(LC-MS/MS)法测定人血浆中的安纳拉唑,并用于研究饮食对其在中国健康人体内的药动学影响。采用d3,13C-安纳拉唑作内标,血浆样品经乙腈沉淀蛋白后,经Extend C18(100 mm×4.6 mm,3.5μm)色谱柱分离,线性范围为5.00~3 000 ng·m L^(-1)(r2>0.995)。本方法成功应用于14名健康受试者空腹及高脂餐后口服40 mg安纳拉唑钠肠溶片的药动学研究。受试者空腹给药后Cmax为(1 020±435)ng·m L^(-1),AUC0-t为(2 370±754)h·ng·m L^(-1),高脂餐后给药后Cmax为(538±395)ng·m L^(-1),AUC0-t为(1 610±650)h·ng·m L^(-1)。与空腹给药相比,饮食条件下安纳拉唑的Cmax降低约47%,AUC0-t降低约32%。结果表明,进食会减少安纳拉唑在人体中的吸收。Anaprazole is a proton pump inhibitor clinically used for curing peptic ulcer. A rapid, sensitive and convenient LC-MS/MS method was first established for the determination of anaprazole in human plasma. d3, 13C-anaprazole was used as internal standard（IS）. After extraction from human plasma by protein precipitation with acetonitrile, all components were separated on an Extend C18 column（100 mm × 4.6 mm, 3.5 μm）. The assay was linear over the concentration range of 5.00-3 000 ng·m L^-1（r2 0.995）. The method was successfully applied to a pharmacokinetic study of 40 mg anaprazole enteric-coated tablets in 14 Chinese healthy volunteers under fasting or high fat diet conditions. Cmax was（1 020 ± 435） ng·m L^-1 and AUC0-t was（2 370 ±754） h·ng·m L^-1 under fasting condition. And Cmax was（538 ± 395） ng·m L^-1 and AUC0-t was（1 610 ± 650） h·ng·m L^-1 under high fat diet condition. The plasma results suggest that the exposure of anaprazole is reduced by the high fat diet.

关 键 词：液相色谱-串联质谱 安纳拉唑 质子泵抑制剂 人体药动学 

分 类 号：R917[医药卫生—药物分析学]