【摘要】 目的建立LC-MS/MS法测定人血浆中培哚普利及其活性代谢产物培哚普利拉的浓度,用于培哚普利/氨氯地平复方制剂中的培哚普利和培哚普利拉的药代动力学研究。方法用Oasis HLB C₁₈（10 mg）固相萃取后,进行液相色谱-质谱分析。色谱柱:Xterra MS C₁₈（150 mm×2.1 mm,3.5μm）,流动相:0.35%甲酸水溶液-甲醇（40∶60）,流速:0.25 m L·min^-1,柱温:45℃。用电喷雾离子源进行正离子多反应监测扫描分析。考察该方法的专属性、标准曲线与定量下限、准确度与回收率、基质效应、残留效应和稳定性。结果血浆中培哚普利和培哚普利拉在0.25⁵0.00 ng·m L^-1内呈良好的线性关系（r>0.990）。在目标化合物出峰时间处,未观察到基质的内源性成分干扰。培哚普利和培哚普利拉的日内、日间相对标准差（RSD）均小于15%。培哚普利萃取回收率为66.3%⁷1.8%,基质效应为91.2%¹09.3%。培哚普利拉萃取回收率为77.1%⁸2.4%,基质效应为90.0%¹04.1%。结论 LC-MS/MS法快速、灵敏、准确、选择性强、重复性好,能够有效地解决复方制剂中的干扰问题,适用于人血浆中培哚普利和培哚普利拉的浓度测定。更多还原

【Abstract】 Objective To establish anultra-high performance liquid chromatography-tandem mass spectrometry（ LC-MS/MS） method for determining the concentrations of perindopril and perindoprilat in human plasma from a pharmacokinetic study of perindopril/amlodipine fixed-combination. Methods The samples were purified by solid phase extraction using Oasis HLB C₁₈（ 10 mg）. The optimal chromatographic behavior was performed on Xterra MS C₁₈（ 150 mm × 2. 1 mm,3. 5 μm）column under the mobile phase which consisted of 0. 35% formic acid solution-methanol（ 40 ∶ 60） and the flow rate was set to be 0. 25 m L·min^-1. The column temperature was 45 ℃. Analytes were detected on a tandem mass spectrometerequipped with an electrospray ionization source and data acquired in the positive multiple reaction monitoring mode（ MRM）. The selectivity,standard curve and low limit of quantification,precision and accuracy,extraction recoveries,matrix effect,carry over and stability were investigated. Results The calibration curves exhibited excellent linearity over the concentration range of 0. 25-50. 00 ng·m L^-1（ r > 0. 990） for both perindopril and perindoprilat. Noendogenous interference was observed at the retention time of the analytes and the carry-over effect was found to be negligible from previous concentrated samples. The intra-day and inter-day relative standard deviations（ RSD） of low,medium and high concentrations of perindopril and perindoprilat were all less than 15%. The average extraction recovery rate was 66. 3%-71. 8% and the average matrix effect was 91. 2%^-109. 3% for perindopril. For perindoprilat,recovery rate was 77. 1%-82. 4%,the average matrix effect was 90. 0%^-104. 1%. Conclusion The LC-MS/MS methodis fast,sensitive,accurate,selective and reproducible,which can solve the interference of fixed-combination,suitable for the determination of the concentration of perindopril and perindopril in human plasma.更多还原