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目的建立一种快速、灵敏并同时测定人体血浆中洛匹那韦(LPV)和利托那韦(RTV)浓度的液相色谱-质谱联用检测方法。方法采用Agilent Eclipse Plus C18柱(4.6 mm×150 mm,3.5μm),流动相为乙腈-水(含0.005 mol.L-1甲酸铵,0.1%甲酸)(90∶10);流速:0.5 mL.min-1,柱温:40℃,以乙酸乙酯为提取剂。采用选择反应监测(SRM)LPV(m/z 629.5→155.1)、RTV(m/z 721.4→296.1)和内标茚地那韦(IDV)(m/z 614.5→465.4)进行测定。结果 LPV高(10 000μg.L-1)、中(1 000μg.L-1)、低(40μg.L-1)3个浓度的平均方法回收率RSD均<15%;线性范围为:20～20 000μg.L-1,回归方程为Y=1.669 9X-0.001 3,r=0.998 4(n=7),定量下限为20μg.L-1。RTV高(2 500μg.L-1)、中(250μg.L-1)、低(10μg.L-1)3个浓度的平均方法回收率RSD均<15%;线性范围为5～5 000μg.L-1,回归方程为Y=1.723 7X-3.274 8×10-4,r=0.998 7(n=7),分析方法的定量下限为5μg.L-1。结论该方法灵敏、准确、简单、快速,可用于LPV和RTV同时应用时两者的临床血药浓度监测和药动学研究。
Objective To establish a rapid, sensitive and simultaneous determination of lopinavir (LPV) and ritonavir (RTV) in human plasma by liquid chromatography-mass spectrometry. Methods The mobile phase was acetonitrile-water (containing 0.005 mol·L-1 ammonium formate, 0.1% formic acid) (90:10) with an Agilent Eclipse Plus C18 column (4.6 mm × 150 mm, 3.5 μm) min-1, column temperature: 40 ℃, with ethyl acetate extractant. Selected assays were performed using selective reaction monitoring (SRM) LPV (m / z 629.5 → 155.1), RTV (m / z 721.4 → 296.1) and internal standard indinavir (IDV) (m / z 614.5 → 465.4). Results The average RSDs of three methods with LPV high (10 000 μg.L-1), medium (1 000 μg.L-1) and low (40 μg.L-1) were all less than 15%. The linear range was 20 ~ 20 000μg.L-1, the regression equation was Y = 1.669 9X-0.001 3, r = 0.998 4 (n = 7), and the lower limit of quantification was 20μg.L-1. The average RSV of RTV high (2 500μg.L-1), middle (250μg.L-1) and low (10μg.L-1) were all less than 15%. The linear range was 5-5000μg. L-1, the regression equation was Y = 1.723 7X-3.274 8 × 10-4, r = 0.998 7 (n = 7). The lower limit of quantitation was 5μg.L-1. Conclusion The method is sensitive, accurate, simple and rapid and can be used to monitor the clinical plasma concentration and pharmacokinetics of both LPV and RTV.