摘要
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。本法采用幽．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，CapcellMGC18柱（100mm×4．6mm，5um）为分析柱，甲醇-乙腈-5mmol·L-1醋酸铵水溶液一甲酸（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0．02～6．00ng·mL-1、贝那普利和贝那普利拉在O．2～1500ng·mL-1内线性良好（P〉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0．2ng·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-解冻循环和乏O℃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。
The study aims to develop a rapid, sensitive and specified method of liquid chromatography with heated electrospray ionization tandem mass spectrometry （LC-HESI/MS/MS） for simultaneous determination of amlodipine, benazepril and benazeprilat in human plasma using amlodipine-d4 and ubenimex as internal standards （1Ss）. Selected reaction monitoring （SRM） with heated electrospray ionization （HESI） was used in the positive mode for mass spectrometric detection. Analytes and ISs were extracted from plasma by simple protein precipitation. The reconstituted samples were chromatographed on a C ~s （100 mm x 4.6 mm, 5 ~tm） column with mixture of methanol-acetonitrile-5 mmol.L-1 ammonium acetate-formic acid （30 ： 30 ： 40 ： 0.1） as mobile phase at a flow rate of 0.6 mL.min-1. The standard curves were demonstrated to be linear in the range of 0.02 to 6.00 ng.mL-1 for amlodipine, 0.2 to 1 500 ng.mL-1 for benazepril and benazeprilat with r2〉0.99 for each analyte. The lower limit of quantitation was identifiable and reproducible at 0.02, 0.2 and 0.2 ng mL-1 for amlodipine, benazepril and benazeprilat, respectively. The intra-day and inter-day precision and accuracy results were within the acceptable limit across all concentrations. The plasma samples were stable after four freeze-thaw cycles and being stored for 93 days at -20 ~C. The method was applied to a pharmacokinetic study of a fixed-dose combination of amlodipine and benazepril on Chinese healthy volunteers.
出处
《药学学报》
CAS
CSCD
北大核心
2014年第1期95-100,共6页
Acta Pharmaceutica Sinica
