Measurement of caffeine and its three primary metabolites in human plasma by HPLC-ESI-MS/MS and clinical application.
Measurement of caffeine and its three primary metabolites in human plasma by HPLC-ESI-MS/MS and clinical application.
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DOI：
10.1002/bmc.3900
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发表时间：
2017-06
期刊：
影响因子：
--
通讯作者：
Laizure SC
中科院分区：
文献类型：
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作者：
Chen F;Hu ZY;Parker RB;Laizure SC
咖啡因是一种温和的兴奋剂，随着能量饮料的广泛使用和新的给药途径（如吸入粉、口服喷雾剂和电子香烟），咖啡因被大量消耗，具有滥用的巨大潜力。最近咖啡因消费的这些变化如何影响咖啡因的处置和滥用潜力越来越受到关注。在人体咖啡因处置的研究中，通常只测量咖啡因浓度;然而，咖啡因的三种主要代谢物（副黄嘌呤、可可碱和茶碱）保留了中枢神经系统刺激活性，这可能有助于整体药理活性和毒性。因此，在评价人类受试者的咖啡因处置时，测量咖啡因及其主要代谢物在科学上更严格。在此，我们报告了一种方法，同时定量咖啡因及其三个主要代谢物在人体血浆中的高效液相色谱-电喷雾串联质谱（HPLC-ESI-MS/MS）。通过简单的蛋白沉淀处理人血浆样品，并使用6分钟梯度程序分离分析物。精密度和准确度均在15%的可接受范围内。简单的样品制备，短的运行时间，灵敏度，并包括咖啡因的主要代谢物，使这种分析方法的最佳研究咖啡因的药代动力学和药效学在人类受试者。
Caffeine is a mild stimulant with significant potential for abuse being consumed in larger doses with the widespread availability of energy drinks and by novel routes of administration such as inspired powder, oral sprays, and electronic cigarettes. How these recent changes in caffeine consumption affecting caffeine disposition and abuse potential is of growing concern. In the study of caffeine disposition in humans, it is common to only measure the caffeine concentration; however, caffeine’s three major metabolites (paraxanthine, theobromine, and theophylline) retain central nervous system stimulant activity that may contribute to the overall pharmacological activity and toxicity. Therefore, it would be scientifically more rigorous to measure caffeine and its major metabolites in the evaluation of caffeine disposition in human subjects. Herein, we report a method for the simultaneous quantification of caffeine and its three major metabolites in human plasma by high-performance liquid chromatography coupled to electrospray tandem mass spectrometry (HPLC-ESI-MS/MS). Human plasma samples were treated by simple protein precipitation and the analytes were separated using a 6-min gradient program. Precision and accuracy were well within in the 15% acceptance range. The simple sample preparation, short runtime, sensitivity, and the inclusion of caffeine’s major metabolites make this assay methodology optimal for the study of caffeine’s pharmacokinetics and pharmacodynamics in human subjects.