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目的:建立HPLC-MS/MS法测定人血浆中喹那普利及其代谢产物喹的浓度。方法:血浆经甲醇蛋白沉淀,使用Agilent C18色谱柱(4.6 mm×150 mm,5μm),以甲醇-0.3%甲酸水(60∶40)为流动相,流速1 m L·min-1,依那普利拉为内标;通过电喷雾离子化四极杆串联质谱,正离子多反应检测方式(MRM)检测,用于定量分析的离子反应分别为m/z 439.2→234.1(喹那普利)、m/z 411.1→206.1(喹那普利拉)、m/z 349.1→206.1(依那普利拉)。结果:喹那普利与喹那普利拉质量浓度分别为4.096~10 000μg·L-1和8.192~2 000μg·L-1时线性关系良好(r2=0.996 6和0.995 9),日内精密度≤6.5%,日间精密度RSD≤8.1%,回收率≥94.9%。喹那普利与喹那普利拉的Tmax分别为(0.6±0.2)h和(1.5±0.4)h,Cmax分别为(243.3±90.1)μg·L-1和(1 008.8±298.4)μg·L-1,t1/2分别为(0.7±0.2)h和(2.3±0.3)h,AUC0-t分别为(220.9±85.6)h·μg·L-1和(3 312.4±967.7)h·μg·L-1。结论:本法经方法学验证,可用于测定药物喹那普利的血药浓度并进行药代动力学研究。
Objective: To establish a HPLC-MS / MS method for the determination of quinapril and its metabolite quinoline in human plasma. Methods: The plasma was precipitated with methanol and applied to a Agilent C18 column (4.6 mm × 150 mm, 5 μm) with methanol-0.3% formic acid (60:40) as the mobile phase at a flow rate of 1 mL · min -1 Pulirac was used as the internal standard. The ion reaction for quantitative analysis was detected by electrospray ionization quadrupole mass spectrometry and positive ion multiple reaction detection (MRM), and m / z 439.2 → 234.1 (quinapril) , M / z 411.1 → 206.1 (quinaprilat), m / z 349.1 → 206.1 (enalaprilat). Results: There was a good linear relationship between quinapril and quinapril concentrations of 4.096-10 000 μg · L-1 and 8.192-2000 μg · L-1, respectively (r2 = 0.996 6 and 0.995 9). Intra-day precision ≤ 6.5%, day precision RSD ≤ 8.1%, recovery ≥ 94.9%. The Tmax of quinapril and quinapril were (0.6 ± 0.2) h and (1.5 ± 0.4) h, respectively, and the Cmax values were (243.3 ± 90.1) μg · L-1 and (1008.8 ± 298.4) μg · (0.7 ± 0.2) h and (2.3 ± 0.3) h respectively, and the AUC0-t were (220.9 ± 85.6) h · μg · L-1 and (3142.4 ± 967.7) h · μg · L-1. Conclusion: This method is validated by methodology and can be used to determine the plasma concentration of quinapril and to study its pharmacokinetics.