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.