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建立液相色谱-加热电喷雾电离串联质谱(LC-HESI/MS/MS)法同时测定人血浆中氨氯地平、贝那普利和贝那普利拉,并研究复方苯磺酸氨氯地平盐酸贝那普利胶囊在中国健康志愿者体内的药物动力学特性。本法采用d4-氨氯地平作为氨氯地平的内标、乌苯美司作为贝那普利和贝那普利拉的内标。血浆样品以沉淀蛋白法进行处理,Capcell MG C18柱(100 mm×4.6 mm,5μm)为分析柱,甲醇-乙腈-5 mmol·L-1醋酸铵水溶液-甲酸(30∶30∶40∶0.1)为流动相进行色谱分离;采用加热电喷雾电离源(HESI),SRM扫描方式。氨氯地平在0.02~6.00 ng·mL-1、贝那普利和贝那普利拉在0.2~1 500 ng·mL-1内线性良好(r2>0.99)。氨氯地平、贝那普利和贝那普利拉定量下限分别可达0.02、0.2和0.2 ng·mL-1,各待测物的日内、日间精密度以及准确度均符合生物样品分析相关要求。血浆样品经历4次冷冻-解冻循环和-20℃放置93天条件下均稳定。本方法适合用于复方苯磺酸氨氯地平盐酸贝那普利胶囊的人体药物动力学研究。
Simultaneous determination of amlodipine, benazepril and benazeprilat in human plasma by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-HESI / MS / MS), and the study of amlodipine besylate Pharmacokinetics of benazepril capsule in healthy Chinese volunteers. This method uses d4-amlodipine as the internal standard for amlodipine, and ubenimex as the internal standard for benazepril and benazeprilat. The plasma samples were treated with the precipitated protein method. Capcell MG C18 column (100 mm × 4.6 mm, 5 μm) was used as the analytical column. The methanol-acetonitrile-5 mmol·L -1 ammonium acetate aqueous solution-formic acid (30:30:40:0.1) As the mobile phase chromatographic separation; using heated electrospray ionization source (HESI), SRM scanning mode. Amlodipine was in the range of 0.02-6.00 ng · mL-1, with a good linearity (r2> 0.99) for benazepril and benazeprilat at 0.2-1 500 ng · mL-1. The lower limit of quantification for amlodipine, benazepril and benazeprilat was 0.02, 0.2 and 0.2 ng · mL-1, respectively. The intra-day and inter-day precision and accuracy of each analyte were in accordance with the requirements of biological sample analysis . Plasma samples were stable under 4 freeze-thaw cycles and at -20 ° C for 93 days. The method is suitable for the pharmacokinetic study of the compound benazepril hydrochloride of amlodipine besylate.