The National Center for Natural Products Research, University of Mississippi, Oxford, MS, USA.
Cardiorespiratory/Metabolic Laboratory, School of Health Studies, University of Memphis, Memphis, TN, USA.
J Chromatogr B Analyt Technol Biomed Life Sci. 2020 Oct 15;1155:122278. doi: 10.1016/j.jchromb.2020.122278. Epub 2020 Aug 2.
Coffea liberica possesses stimulant properties without accumulating the methylxanthine caffeine. The basis for this peculiar observation is that methylurates (e.g., theacrine and methylliberine) have replaced caffeine. The stimulant properties of methylurates, alone and in combination with caffeine, have recently been investigated. However, human pharmacokinetics and LC-MS/MS methods for simultaneous measurement of methylxanthines and methylurates are lacking. To address this deficiency, we conducted a pharmacokinetic study in which subjects (n = 12) were orally administered caffeine (150 mg), methylliberine (Dynamine™, 100 mg), and theacrine (TeaCrine®, 50 mg) followed by blood sampling over 24 h. Liquid-liquid extraction of plasma samples containing purine alkaloids and internal standard (C-Caffeine) were analyzed using a C18 reversed-phase column and gradient elution (acetonitrile and water, both containing 0.1% formic acid). A Waters Xevo TQ-S tandem mass spectrometer (positive mode) was used to detect caffeine, methylliberine, theacrine, and IS transitions of m/z 195.11 → 138.01, 225.12 → 168.02, 225.12 → 167.95, and 198.1 → 140.07, respectively. The method was validated for precision, accuracy, selectivity, and linearity and was successfully applied to characterize the oral pharmacokinetics of caffeine, methylliberine, and theacrine in human plasma. Successful development and application of LC-MS/MS-based methods such as ours for the simultaneous measurement of methylxanthines and methylurates are essential for the characterization of potential pharmacokinetic and pharmacodynamic interactions.
利比里卡咖啡含有刺激物，不会积累甲基黄嘌呤咖啡因。这种特殊观察的基础是甲基尿酸盐（例如，可可因和甲基育亨宾）已取代了咖啡因。甲基尿酸盐的刺激作用，单独使用和与咖啡因联合使用，最近已经进行了研究。然而，目前缺乏同时测量甲基黄嘌呤和甲基尿酸盐的人体药代动力学和 LC-MS/MS 方法。为了解决这一不足，我们进行了一项药代动力学研究，其中 12 名受试者口服给予咖啡因（150mg）、甲基育亨宾（Dynamine™，100mg）和可可因（TeaCrine®，50mg），然后在 24 小时内采集血液样本。含有嘌呤生物碱和内标（C-咖啡因）的血浆样品采用液液萃取，使用 C18 反相柱和梯度洗脱（乙腈和水，均含有 0.1%甲酸）进行分析。采用 Waters Xevo TQ-S 串联质谱仪（正模式）检测咖啡因、甲基育亨宾、可可因和内标（m/z195.11→138.01、225.12→168.02、225.12→167.95 和 198.1→140.07）的转换。该方法经过了精密度、准确度、选择性和线性验证，并成功应用于人类血浆中咖啡因、甲基育亨宾和可可因的口服药代动力学特征描述。开发和应用我们这样的基于 LC-MS/MS 的方法来同时测量甲基黄嘌呤和甲基尿酸盐对于描述潜在的药代动力学和药效学相互作用至关重要。
