福辛普利拉血药浓度的LC-MS/MS法测定及其人体药动学研究  

Determination of Plasma Concentration of Fosinoprilat by LC-MS/MS and Study on Its Pharmacokinetics in Healthy Volunteers

作　　者：周文佳[1] 王蒙[1] 黄明[1] 华雯妍[1] 张全英[1] 

机构地区：[1]苏州大学附属第二医院Ⅰ期临床试验研究室,江苏苏州215004

出　　处：《药学进展》2012年第3期123-127,共5页Progress in Pharmaceutical Sciences

摘　　要：目的:建立福辛普利的活性代谢产物福辛普利拉血药浓度的LC-MS/MS测定方法,考察福辛普利钠片经中国健康受试者口服后的药动学特性。方法:采用甲醇直接沉淀蛋白法处理血浆样本;LC采用WATERS XTerraRP18柱(150 mm×4.6 mm,5μm),柱温为48℃,流动相为6 mmoL.L-1醋酸铵水溶液(用氨水调节至pH 10.2)-甲醇(57∶43),流速为1.0 mL.min-1,进样量为40μL;MS应用三重四极杆串联质谱仪,采用电喷雾离子源、负离子电离模式及多反应监测,检测离子选择福辛普利拉离子(m/z:434.2→236.9)和内标瑞巴派特离子(m/z:369.0→169.9)。20名受试者口服福辛普利钠片10 mg后,在不同时间点采集血浆样本,采用建立的LC-MS/MS法测定福辛普利拉血药浓度,计算药动学参数。结果:福辛普利拉血药浓度在0.5005～300.3μg.L-1范围内线性关系良好,最低定量限为0.5μg.L-1。福辛普利拉的Cmax为(148.4±43.9)μg.L-1,Tmax为(4.05±0.76)h,AUC0-48 h为(1 315±342)μg.h.L-1,AUC0-∞为(1 335±341)μg.h.L-1,CL/F为(7.957±1.969)L.h-1,Vd为(103.9±41.2)L,t1/2为(8.94±2.62)h。结论:该法简便、准确、灵敏,适用于福辛普利钠片的临床药动学研究。[ Abstract] Objective： To establish a LC-MS/MS method for the determination of plasma concentration of fosinoprilat, an active metabolite of fosinopril, and to investigate the pharmacokinetie profiles after single oral administration of fosinopril sodium tablets in Chinese healthy volunteers. Methods： The plasma samples were pre-treated by protein precipitation with methanol. LC was performed using a WATERS XTerra RP18 column （150 mm x4.6 ram, 5 Ixm） at a column temperature of 48 °C, with 6 mmoL.L-1 ammonium acetate （ adjusted to pH 10. 2 with ammonia water） -methanol （ 57： 43） as mobile phase at a flow rate of 1.0 mL.min-1 and an injection volume of 40 μL. MS was performed using a triple-quadrupolemass spectrometer, with negative electron spray ionization （ESI） mode and multiple reaction monitoring （MRM） ; the extracted ions monitored following MRM transitions were m/z 434. 2--~236. 9 for fosinoprilat and m/z 369. 0--~169. 9 for the internal standard rebamipide. A single oral dose of 10 mg fosinopril sodium tablets was given respectively to 20 healthy subjects, followed by taking plasma samples at different time points, determining plasma concentration of fosinoprilat by the established LC-MS/MS method and calcula- ting the pharmacokinetic parameters by a DAS 2. 0 program. Results： The linear range of plasma concentra- tion of fosinoprilat was 0. 500 5-300. 3 μg L-1. The lowest limit of quantitation was 0. 500 5 ixg.L-1. C Tmax, AUC0-48 h, AUC00-1, CIMF, Va and t1/2 of fosinoprilat were （ 148.4 ±43.9） μg.L-1, （4. 05 ±0.76） h,（1 315 ±342） μg-h-L-1,（1 335± 341） μg.h.L-l, （7. 957 ±1. 969） L-h-t,（103.9±41.2） Land （ 8.94 ± 2.62） h, respectively. Conclusion： The method is simple, accurate, sensitive and practicable for the clinical pharmacokinetic study of fosinopril sodium tablets.

关 键 词：福辛普利拉 福辛普利钠片 血药浓度 药动学参数 液相-串联质谱法 

分 类 号：O657.63[理学—分析化学] R969.1[理学—化学]