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目的:建立人血浆中多潘立酮浓度的LC-MS/MS测定法,用于临床试验中多潘立酮血药浓度的测试。方法:以泮托拉唑为内标,血浆样本经0.1 mol·L-1氢氧化钠溶液碱化后用乙醚萃取处理。采用Agilent TC-C18色谱柱(4.6 mm×150 mm,5μm)为分析柱,Phenomenex Gemini C18柱(4 mm×3.0 mm,10μm)为保护柱,以甲醇-20 mmol·L-1甲酸铵水溶液(70∶30,v/v)为流动相,使用电喷雾离子源(ESI),以正离子多反应监测(MRM)方式进行检测。结果:每个样本分析时间为5 min。血浆中内源性物质对测定无干扰,多潘立酮线性范围为0.6970～44.60μg.L-1,定量下限(LLOQ)为0.6970μg.L-1。日内、日间精密度(RSD)均小于10%,多潘立酮与内标的平均提取回收率分别为100.7%和98.7%,平均基质效应分别为为101.4%和98.9%,且均不存在浓度依赖性。结论:本方法特异性强,灵敏度高,测定结果可靠,适用于临床试验中血浆样本的高通量分析。
OBJECTIVE: To establish a LC-MS / MS method for the determination of domperidone in human plasma and to test the plasma concentration of domperidone in clinical trials. Methods: Pantoprazole was used as internal standard. The plasma samples were alkalized by 0.1 mol·L-1 sodium hydroxide solution and extracted with ether. The analytical column was Agilent TC-C18 (4.6 mm × 150 mm, 5 μm). Phenomenex Gemini C18 column (4 mm × 3.0 mm, 10 μm) was used as the guard column. The column was eluted with methanol-20 mmol·L -1 ammonium formate 70:30, v / v) as the mobile phase, using positive ion multiple reaction monitoring (MRM) using electrospray ionization source (ESI). Results: Each sample analysis time was 5 min. Plasma endogenous substances had no interference with the assay. The linear range of domperidone was 0.6970 ~ 44.60μg.L-1, and the limit of quantification (LLOQ) was 0.6970μg.L-1. The intra-day and inter-day RSD were all less than 10%. The average recoveries of domperidone and internal standard were 100.7% and 98.7%, respectively. The average matrix effects were 101.4% and 98.9% respectively, and no concentration dependence was found. Conclusion: The method is specific, sensitive and reliable. It is suitable for high-throughput analysis of plasma samples in clinical trials.