Determination of afloqualone in human plasma using liquid chromatography/tandem mass spectrometry: Application to pharmacokinetic studies in humans.
Determination of afloqualone in human plasma using liquid chromatography/tandem mass spectrometry: Application to pharmacokinetic studies in humans.
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使用液相色谱/串联质谱法测定人血浆中的阿氟喹酮：在人体药代动力学研究中的应用。
DOI：
10.1016/j.talanta.2007.04.039
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发表时间：
2007
期刊：
影响因子：
--
通讯作者：
K. Kwon
中科院分区：
文献类型：
--
作者：
Hwi‐yeol Yun;Seo;H. Jeong;Y. Yoon;S. Sohn;S. K. Kim;W. Kang;K. Kwon
使用 API2000 和 API4000 液相色谱串联质谱 (LC/MS/MS) 系统开发并比较了两种测定人血浆中中枢作用肌肉松弛剂阿氟喹酮的方法。在 API2000 LC/MS/MS 系统中，使用甲基叔醚从血浆中提取阿氟喹酮和内标甲喹酮。干燥有机层后，将残余物在流动相（0.1% 甲酸-乙腈:0.1% 甲酸缓冲液，80:20 v/v）中重构，并注射到反相 C18 柱上。等度流动相以0.2ml/min洗脱。在多反应监测模式下监测到的阿氟喹酮和甲喹酮的离子跃迁分别为 m/z 284→146 和 251→117。 API4000LC/MS/MS 系统的样品制备涉及使用有机混合物（甲醇：10% ZnSO4=8:2）进行简单的蛋白质沉淀。在多反应监测模式下监测到的阿氟喹酮和甲喹酮的离子跃迁分别为 m/z 284→146 和 251→131。两次测定的精密度变异系数均小于11.8%，准确度超过91.5%，阿氟喹酮的定量限为0.5ng/ml，检出限为0.1ng/ml。使用两种方法测量健康受试者单次口服 20 mg 剂量的阿氟喹酮后的血浆阿氟喹酮浓度。在随后的方法应用过程中，我们观察到使用蛋白质沉淀法制备的高浓度血浆样品（>7ng/ml）导致阿氟喹酮浓度比使用液液萃取法制备的血浆样品高约20%。我们认为这种现象与样品的清洁度及其化学性质有关。
Two methods for determining the central-acting muscle relaxant afloqualone in human plasma were developed and compared using API2000 and API4000 liquid chromatography tandem mass spectrometry (LC/MS/MS) systems. In the API2000 LC/MS/MS system, afloqualone and the internal standard methaqualone were extracted from plasma using a methyl-tertiary ether. After drying the organic layer, the residue was reconstituted in a mobile phase (0.1% formic acid–acetonitrile:0.1% formic acid buffer, 80:20 v/v) and injected onto a reversed-phase C18column. The isocratic mobile phase was eluted at 0.2ml/min. The ion transitions monitored in multiple reaction-monitoring mode were m/z 284→146 and 251→117 for afloqualone and methaqualone, respectively. Sample preparation for the API4000LC/MS/MS system involved simple protein precipitation with an organic mixture (methanol:10% ZnSO4=8:2). The ion transitions monitored in multiple reaction-monitoring mode were m/z 284→146 and 251→131 for afloqualone and methaqualone, respectively. In both assays, the coefficient of variation of the precision was less than 11.8%, the accuracy exceeded 91.5%, the limit of quantification was 0.5ng/ml, and the limit of detection was 0.1ng/ml for afloqualone. Two methods were used to measure the plasma afloqualone concentration in healthy subjects after a single oral 20-mg dose of afloqualone. During subsequent application of the methods, we observed that high-concentration plasma samples (>7ng/ml) prepared using the protein precipitation method resulted in about 20% higher afloqualone concentrations than with plasma samples prepared using the liquid–liquid extraction method. We believe that this phenomenon was related to the cleanness of the sample and its chemical nature.