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建立液相色谱-串联质谱法(LC-MS/MS)测定人血浆中洛匹那韦(LPV)、利托那韦(RTV)的浓度。血浆样品经碱化沉淀蛋白后,经乙酸乙酯液-液萃取,以甲醇-0.1%甲酸水溶液(80:20)为流动相,Agilent ZORBAX Eclipse XDB-C18(150mm×4.6mmID,5μm)柱分离;采用电喷雾电离源,以多反应监测(MRM)方式进行正离子检测,用于定量分析的离子对LPV为629.6→155.2,RTV为721.4→268.2,内标替米沙坦(TEL)为515.2→276.2。测定血浆中LPV线性范围为62.5～10000ng·mL-1,检测限为15pg·mL-1,RTV的线性范围为12.5～2000ng·mL-1,检测限为8pg·mL-1,r均大于0.99。日内和日间精密度均小于15%,提取回收率均大于75%。该法选择性强、灵敏度高、重现性好,能同时快速、准确测定人血浆LPV和RTV浓度,为临床治疗药物浓度监测(TDM)奠定基础。
The concentration of lopinavir (LPV) and ritonavir (RTV) in human plasma was determined by liquid chromatography-tandem mass spectrometry (LC-MS / MS) Plasma samples were alkalinized and the proteins were separated by liquid-liquid extraction with ethyl acetate-methanol 0.1% formic acid (80:20) as mobile phase on an Agilent ZORBAX Eclipse XDB-C18 column (150 mm × 4.6 mm ID, 5 μm) . The electrospray ionization source was used for positive ion detection with multiple reaction monitoring (MRM). The ion pair for quantitative analysis was 629.6 → 155.2 for LPV, 721.4 → 268.2 for RTV and 515.2 for telmisartan → 276.2. The linear range of LPV was 62.5 ~ 10000ng · mL-1, the limit of detection was 15pg · mL-1, the linear range of RTV was 12.5 ~ 2000ng · mL-1, the limit of detection was 8pg · mL-1, r was greater than 0.99 . The intra-day and inter-day precision were less than 15%, extraction recovery rates were greater than 75%. The method is selective, sensitive and reproducible. It can simultaneously and rapidly determine the concentration of LPV and RTV in human plasma and lay a foundation for the clinical treatment of drug concentration monitoring (TDM).