LC-MS/MS法测定人血浆中多潘立酮的浓度

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,5 μm)为分析柱,Phenomenex Gemini C₁₈ 柱(4 mm×3.0 mm,10 μm)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0.6970~44.60 μg·L^-1 ,定量下限(LLOQ)为0.6970 μg·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 an LC-MS/MS method for the determination of domperidone in human plasma,and to assay the biological samples from clinical trials. Mehods: Pantoprazole was used as internal standard.Alkalified by 0.1 mol·L^-1 sodium hydroxide solution,plasma samples were extracted with ethyl ether.The extractive was separated on an Agilent TC-C₁₈ column(4.6 mm×150 mm,5 μm) guarded by a Phenomenex Gemini C₁₈ column(4 mm×3.0 mm,10 μm).The mobile phase consisted of methanol-20 mmol·L^-1 ammonium formate(70∶ 30,v/v).Electrospray ionization (ESI) source was applied and operated in the positive multiple reaction monitoring (MRM) mode. Results: Each analysis was completed within 5 min.Chromatograms showed no endogenous interfering peaks with blank samples.The linear calibration curve was obtained over the concentration on range of 0.6970-44.60 μg·L^-1.The limit of quantification was 0.6970 μg·L^-1.The inter-and intra-day precision(RSD) was less than 10%.The average extraction recovery of domperidone and pantorazole was respectively 100.7% and 98.7%,and the average matrix effects of of domperidone and pantorazole were respectively 101.4% and 98.9%,in which no concentration dependences were observed. Conclusion: The method is specific,sensitive and accuracy,and proved to be suitable for the determination of domperidone in human plasma in clinical plasma samples.