中国临床药学杂志

目的建立奥美拉唑血药浓度测定的LC-MS/MS检测方法,并研究奥美拉唑在兔体内的药动学特征。方法 5只日本大耳白兔耳缘静脉给予奥美拉唑2 mg·kg^-1,给药后10、20、30、45、60、75、90、120、150、180、240、300、360 min各采血0.5 mL,分离血浆后,加入内标奥沙西泮,以碳酸钠碱化后用乙酸乙酯萃取。流动相为乙腈-0.1%甲酸(40∶60,V/V),流速为O.3 mL·min^-1。经Zorbax SB-C₁₈柱(150 mm×2.1 mm,5μm)分离。采用电喷雾离子源,以多反应监测方式进行正离子检测,奥美拉唑m/z 346→198,奥沙西泮m/z 287→269。结果奥美拉唑血药浓度在2～1 800μg·L^-1内线性关系良好,萃取回收率>65%,日内和日间RSD<10%。奥美拉唑2 mg·kg^-1静脉给药后,AUC_0→t(922.925±214.175)μg·h·L^-1,AUC_0→∞(936.61±205.951)μg·h·L^-1,t_1/2(1.88±0.802)h,V(6.501±4.067)L·kg^-1,ρ_max(1 376.94±365.795)μg·L^-1。结论奥美拉唑在兔体内按二房室模型转运,代谢快,半衰期短;LC-MS/MS法操作简便、灵敏度高,适用于探针药奥美拉唑的药动学研究。

AIM To establish a sensitive and selective LC-MS/MS method for the determination of omeprazole, and to study its pharmacokinetic characteristics in rabbits.METHODS The 0.5 mL of plasma samples were collected at 10,20,30,45,60,75,90,120,150,180,240,300 and 360 min after five Japanese rabbits were received a single intravenous administration of 2 mg·kg^-1 omeprazole.Omeprazole was extracted from rabbit plasma by liquid-liquid extraction, and then analyzed on a Zorbax SB-C₁₈(150 mm×2.1 mm,5μm) column.The mobile phase consisted of acetonitrile -0.1%formic acid(40?60,V/V)at a flow rate of 0.3 mL·min^-1.A Bruker Esquire HCT mass spectrometer equipped with electrospray ionization source was used as detector and was operated in the positive ion mode.Quantification was performed using multiple reaction monitoring of the transitions m/z 346→198 and m/z 287→269 for omeprazole and the internal standard,respectively.RESULTS The linear calibration curves were obtained in the concentration range of 2-1 800μg·L^-1.The lower limit of quantification was 2μg·L^-1.The intra-day and inter-day relative standard deviations were less than 10%.The pharmacokinetics of omeprazole was as follows:AUC_0→t(922.925±214.175)μg·h·L^-1,AUC_0→∞(936.61±205.95l)μg·h·L^-1,t_1/2(1.88±0.802) h,V(6.501±4.067) L·kg^-1,andρ_max(1 376.94±365.795)μg·L^-1.CONCLUSION The pharmacokinetic parameters of omeprazole in rabbits are fitted to two compartment model,and omeprazoloe is eliminated fastly.The method is rapid,selective and is proved to be suitable for pharmacokinetic study for omeprazole.