Olesti Eulàlia, Pujadas Mitona, Papaseit Esther, Pérez-Mañá Clara, Pozo Óscar J, Farré Magí, de la Torre Rafael
Integrative Pharmacology and Systems Neuroscience Research Group, Neurosciences Research Program, IMIM (Hospital del Mar Medical Research Institute), Dr. Aiguader 88, Barcelona 08003, Spain.
Pompeu Fabra University (CEXS-UPF), Dr. Aiguader 88, Barcelona 08003, Spain.
J Anal Toxicol. 2017 Mar 1;41(2):100-106. doi: 10.1093/jat/bkw120.
Increasing consumption has been observed among young people of new psychoactive substances, including synthetic cathinone derivatives. The most well known of these is mephedrone whose use has been related to acute intoxication and fatality. Several methods able to detect mephedrone have been reported, although to date, none have been applied to human pharmacokinetic studies in a controlled setting. We developed a gas chromatography-mass spectrometry technique for mephedrone quantification in human plasma and urine. Plasma after deproteinization and urine were submitted to a liquid-liquid extraction and derivatization of the extract with MSTFA prior to analysis. Calibration curves covered concentration ranges in plasma between 5 and 300 ng/mL and in urine between 20 and 1,500 ng/mL. The method has been successfully applied to biological samples obtained from a pilot clinical trial intended to evaluate the human pharmacology of mephedrone and its relative bioavailability and pharmacokinetics. Six healthy males were administered 150 mg of mephedrone by the oral route in a randomized, double-blind, cross-over controlled trial. Peak plasma concentration (Cmax = 122.6 ± 32.9 ng/mL) was reached at 1 hour (0.5-2 h) post-drug administration. Mephedrone showed a rapid elimination half-life (t1/2 = 2.2 h) compared to other psychostimulants. Less than 15% of the dose was excreted in urine as a free-form. Mephedrone concentrations displayed a relevant inter-subject variability.
在年轻人中，新型精神活性物质（包括合成卡西酮衍生物）的消费量一直在增加。其中最广为人知的是甲麻黄碱，其使用与急性中毒和死亡有关。已经报道了几种能够检测甲麻黄碱的方法，尽管迄今为止，尚无任何方法应用于受控环境下的人体药代动力学研究。我们开发了一种气相色谱 - 质谱技术，用于定量测定人血浆和尿液中的甲麻黄碱。血浆经去蛋白处理后，尿液进行液 - 液萃取，并在分析前用MSTFA对萃取物进行衍生化。校准曲线覆盖血浆浓度范围为5至300 ng/mL，尿液浓度范围为20至1500 ng/mL。该方法已成功应用于从一项旨在评估甲麻黄碱人体药理学及其相对生物利用度和药代动力学的初步临床试验中获得的生物样本。在一项随机、双盲、交叉对照试验中，6名健康男性口服150 mg甲麻黄碱。给药后1小时（0.5 - 2小时）达到血浆峰浓度（Cmax = 122.6 ± 32.9 ng/mL）。与其他精神兴奋剂相比，甲麻黄碱的消除半衰期较短（t1/2 = 2.2小时）。剂量中不到15%以游离形式经尿液排泄。甲麻黄碱浓度显示出受试者间的显著变异性。
