UPLC-MS/MS同时测定人血浆中依那普利和依那普利拉以及应用于空腹和餐后药动学研究（英文）

Simultaneous Determination of Enalapril and Enalaprilat in Human Plasma by UPLC-MS/MS and Its Clinical Application under Fasting and Fed Conditions

建立了液相色谱-串联质谱(UPLC-MS/MS)法同时测定人血浆中的依那普利(1)和依那普利拉(2)。流动相为80%甲醇(含0.5%甲酸)∶0.5%甲酸,总流速0.3 ml/min,选用Waters Acquity UPLC BEH色谱柱,采用电喷雾电离源正离子模式、多反应监测(MRM)进行定量分析。1和2分别在0.5～200 ng/ml和0.2～80 ng/ml范围内线性关系良好,回收率为99.71%和99.59%。1的日内、日间精密度小于2.9%,2的日内、日间精密度小于9.4%。1和2准确度偏差范围为-2.86%～1.04%。验证结果显示,应用本法测定人血浆中1及2无明显基质效应,高脂基质及溶血基质不影响方法准确性。本方法成功应用于1及2空腹及餐后的药动学研究。

A rapid, sensitive and selective UPLC-MS/MS method was developed for the simultaneous determination of enalapril and enalaprilat in human plasma. Chromatographic separation was achieved on a Waters Acquity UPLC BEH column, with the mobile phase of 80% methanol （containing 0.5% formic acid, A） and 0.5% formic acid （B） at a flow rate of 0.3 ml/min. A tandem mass spectrometric detection with an electrospray ionization （ESI） interface was conducted via multiple reaction monitoring （MRM） under positive ionization mode. Linear calibrations were achieved in ranges of 0.5-200 ng/ml for enalapril and 0.2-80 ng/ml for enalaprilat in human plasma. The intra- and inter-day precisions were below 2.9 % for enalapril and below 9.4 % for enalaprilat, and the deviations of accuracies were -2.86%-1.04%. The average recoveries of enalapril and enalaprilat were 99.71% and 99.59 %, respectively. There was no significant matrix effect, hemolyzed effect or hyperlipidemic effect for enalapril and enalaprilat. This method was successfully applied to a fasting and fed phannacokinetic study of enalapril maleate in Chinese volunteers.