1. In vitro metabolic profile of mexedrone, a mephedrone analog, studied by high‐ and low‐resolution mass spectrometry
- Author
-
Fabio De-Giorgio, Xavier de la Torre, Monica Mazzarino, Matteo Marti, Angelica Guglielmelli, Francesco Botrè, and Cristian Camuto
- Subjects
Cathinone ,Mexedrone ,Socio-culturale ,Pharmaceutical Science ,Mass spectrometry ,Tandem mass spectrometry ,Methamphetamine ,Analytical Chemistry ,Hydroxylation ,chemistry.chemical_compound ,Tandem Mass Spectrometry ,medicine ,Humans ,Environmental Chemistry ,LS7_5 ,Chromatography, High Pressure Liquid ,Spectroscopy ,LS7_9 ,Chromatography ,mexedrone ,synthetic cathinones ,Chemistry ,in vitro metabolism ,mephedrone analogs ,novel psychoactive substances ,Triple quadrupole mass spectrometer ,Metabolome ,Microsomes, Liver ,Microsome ,Drug metabolism ,medicine.drug - Abstract
Mexedrone is a synthetic cathinone structurally related to mephedrone, which belongs to the class of N-alkyl cathinone derivatives, whose metabolic profile has not been fully clarified yet. This study considers the in vitro phase I metabolism of mexedrone, to pre-select the most appropriate marker(s) of intake. Mexedrone was incubated in the presence of either human liver microsomes or single recombinant CYP450 isoforms. The metabolic profile was outlined by ultra-high-performance liquid chromatography coupled to both high- and low-resolution mass spectrometry. In detail, the phase I metabolic profile of mexedrone was initially defined by a time-of-flight analyzer, while the chemical structures of the detected metabolites and the potential presence of minor metabolites were subsequently studied by tandem mass spectrometry, using a triple quadrupole analyzer. The main phase I metabolic reactions were hydroxylation and N- and O-dealkylation. The CYP450 isoforms most involved were CYP2C19, responsible for the formation of both hydroxylated and dealkylated metabolites, followed by CYP2D6 and CYP1A2, involved in the hydroxylation reactions only. Finally, a significant fraction of mexedrone unchanged was also detected. Based on this evidence, the most appropriate markers of intake are mexedrone unchanged and the hydroxylated metabolites.
- Published
- 2021