Methylone and MDMA Pharmacokinetics Following Controlled Administration in Humans
Poyatos, Lourdes (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Lo Faro, Alfredo Fabrizio (Università Politecnica delle Marche)
Berardinelli, Diletta (Università Politecnica delle Marche)
Sprega, Giorgia (Università Politecnica delle Marche)
Malaca, Sara (Università Politecnica delle Marche)
Pichini, Simona (Istituto Superiore di Sanità)
Huestis, Marilyn A. (Thomas Jefferson University)
Papaseit, Esther (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Pérez-Mañá, Clara (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Busardo, Francesco Paolo (Università Politecnica delle Marche)
Farre, Magi (Institut Germans Trias i Pujol. Hospital Universitari Germans Trias i Pujol)
Universitat Autònoma de Barcelona

Data:	2022
Resum:	The aim of this study is to define, for the first time, human methylone and HMMC plasma pharmacokinetics following controlled administration of 50-200 mg methylone to 12 male volunteers. A new LC-MS/MS method was validated to quantify methylone, MDMA, and their metabolites in plasma. The study was a randomized, cross-over, double-blinded and placebo-controlled study, with a total of 468 plasma samples collected. First, 10 µL of MDMA-d, MDA-d and methylone-d internal standards were added to 100 µL of plasma. Two mL of chloroform and ethyl acetate 9:1 (v / v) were then added, mixed well and centrifuged. The supernatant was fortified with 0. 1 mL acidified methanol and evaporated under nitrogen. Samples were reconstituted with a mobile phase and injected into the LC-MS/MS instrument. The method was fully validated according to OSAC guidelines (USA). Methylone plasma concentrations increased in a dose-proportional manner, as demonstrated by the increasing maximum concentration (Cmax) and area under the curve of concentrations (AUC). Methylone Cmax values were reported as 153, 304, 355 and 604 ng/mL, AUC0-24 values were reported as 1042. 8, 2441. 2, 3524. 4 and 5067. 9 h·ng/mL and T values as 5. 8, 6. 4, 6. 9 and 6. 4 h following the 50, 100, 150 and 200 mg doses, respectively. Methylone exhibited rapid kinetics with a Tmax of 1. 5 h for the 50 mg dose and 2 h approximately after all the other doses. HMMC exhibited faster kinetics compared to methylone, with a Cmax value that was 10-14-fold lower and an AUC0-24 value that was 21-29-fold lower. Methylone pharmacokinetics was linear across 50-200 mg oral doses in humans, unlike the previously described non-linear oral MDMA pharmacokinetics. An LC-MS/MS method for the quantification of methylone, MDMA and their metabolites in human plasma was achieved. Methylone exhibited linear pharmacokinetics in humans with oral doses of 50-200 mg.
Ajuts:	Instituto de Salud Carlos III PI17/01962 Instituto de Salud Carlos III PI20/00879
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Humans ; LC-MS/MS ; MDMA ; Methylone ; Pharmacokinetics
Publicat a:	International journal of molecular sciences, Vol. 23 (november 2022) , ISSN 1422-0067

DOI: 10.3390/ijms232314636
PMID: 36498963

13 p, 819.4 KB

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