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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.

GC–MS Quantification Method for Mephedrone in Plasma and Urine: Application to Human Pharmacokinetics