Enantioselective determination of (R)- and (S)-lansoprazole in human plasma by chiral liquid chromatography with mass spectrometry and its application to a stereoselective pharmacokinetic study
Enantioselective determination of (R)- and (S)-lansoprazole in human plasma by chiral liquid chromatography with mass spectrometry and its application to a stereoselective pharmacokinetic study
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DOI：
10.1002/jssc.201500653
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发表时间：
2015-11-01
影响因子：
3.1
通讯作者：
Wang, Yongqing
中科院分区：
文献类型：
--
作者：
Sun, Luning;Cao, Yang;Wang, Yongqing
建立了手性液相色谱-串联质谱同时测定人血浆中(R)-兰索拉唑和(S)-兰索拉唑的对映选择性方法。以乙腈为蛋白质沉淀剂，从血浆中提取兰索拉唑对映体和内标物埃索美拉唑。在Chiralpak IC色谱柱（150 mm × 4.6 mm, 5 μ m）上，柱温为30℃，在9.0 min内完成基线手性分离。流动相为10 mm醋酸铵溶液，含0.05%乙酸/乙腈（50:50,v/v）。质谱分析采用QTrap 5500质谱联用正离子模式电喷雾电离源进行。用m/z 370.1 -> 252.1和346.1 -> 198.1多反应监测跃迁分别定量兰索拉唑对映体和埃索美拉唑。各对映体均无明显基质效应，在5.00 ~ 3000 ng/mL范围内均呈线性关系，日内、日间精密度均在10.0%以下，准确度为-3.8 ~ 3.3%。分析物在研究过程中是稳定的。在样品储存、制备和分析过程中均未观察到手性反转。将该方法应用于静脉给药右兰索拉唑和外消旋兰索拉唑后人体立体选择性药代动力学研究。
A simple and enantioselective method was developed and validated for the simultaneous determination of (R)- and (S)-lansoprazole in human plasma by chiral liquid chromatography with tandem mass spectrometry. Lansoprazole enantiomers and internal standard (esomeprazole) were extracted from plasma using acetonitrile as protein precipitating agent. Baseline chiral separation was achieved within 9.0 min on a Chiralpak IC column (150 mm x 4.6 mm, 5 mu m) with the column temperature of 30 degrees C. The mobile phase consisted of 10 mM ammonium acetate solution containing 0.05% acetic acid/acetonitrile (50: 50, v/v). The mass spectrometric analysis was performed using a QTrap 5500 mass spectrometer coupled with an electrospray ionization source in positive ion mode. The multiple reactions monitoring transitions of m/z 370.1 -> 252.1 and 346.1 -> 198.1 were used to quantify lansoprazole enantiomers and esomeprazole, respectively. For each enantiomer, no apparent matrix effect was found, the calibration curve was linear over 5.00-3000 ng/mL, the intra- and inter-day precisions were below 10.0%, and the accuracy was -3.8 to 3.3%. Analytes were stable during the study. No chiral inversion was observed during sample storage, preparation procedure and analysis. The method was applied to the stereoselective pharmacokinetic studies in human after intravenous administration of dexlansoprazole or racemic lansoprazole.