液相色谱-串联质谱法测定人血浆中卡托普利的浓度

Determination of Captopril in Human Plasma by Liquid Chromatography-Tandem Mass Spectrometry

建立了测定人血浆中卡托普利的LC／MS／MS法。取血浆0．2mL．用对溴苯甲酰甲基溴进行衍生化．经甲醇沉淀蛋白后，以甲醇-10mmol／L乙酸铵．甲酸（80／20／0．4，V／V）为流动相，用Zorbax SB—C18柱分离，通过配有电喷雾离子化源的四极杆-线性离子阱质谱仪，以多反应监测（MRM）方式进行检测。用于定量分析的离子反应分别为m／z416→m／z216（卡托普利衍生物）和m／z28→m/z 193（安定）。卡托普利的线性范围为2．5—1000μg/L，最低定量限为2．5μg/L，样品分析时间为2．0min。该法精密、准确，在灵敏度和分析速度上优于以往文献报道，适用于游离型卡托普利血药浓度的监测和药动学研究。

A rapid, selective and sensitive method for the determination of captopril in human plasma has been developed. Captopril in plasma was trapped with p-bromophenacyl bromide （p-BPB） to give the adduct of captopril-p-BPB, then the captopril-p-BPB adduct and the internal standard diazepam were isolated from plasma by protein precipitation with methanol. High performance liquid chromatography separation was performed on Zorbax SB-C18 colunm at a flow rate of 1.0 mL/min with an analysis time of 2.0 minutes, and the mobile phase consisted of methanol-10 mmol/L ammonium acetate buffer-formic acid （80：20：0.4, WV）. The detection was performed by Q-trap^TM liquid chromatography tandem mass spectrometric（MS/MS） system with an electrospray ionization（ESI） interface in multiple reaction-monitoring mode. The linearity between the cap- topril concentration and the ratio of peak area was in the range of 2.5 - 1000 μg/L. The lower limit of quanti- fication of the method was 2.5 μg/L. The method, which offers advantages of specificity, speed, and sensitivity is proved to be suitable for clinical investigation of captopril pharmacokinetics.