Amphetamine-derived new psychoactive substances : metabolic fate and toxicological detectability of methiopropamine, three methyl-amphetamine isomers, camfetamine, 5-APB, 6-APB, 5-MAPB, and 6-MAPBin urine and human liver preparations using GC-MS, LC-MSn, and LC-HR-MSn techniques

摘要

The number of new psychoactive substances identified each year by the EMCDDA is increasing rapidly, as in 2014, 101 new compounds have been identified. One important structural group of NPS are the phenethylamines. In the presented studies, the metabolic fate and the toxicological detection of different amphetamine-derived compounds belonging to the phenethylamine group of NPS have been investigated. Using GC-MS and/or LC-High-Resolution-MSn, the main phase I metabolic step observed for the compounds containing the methamphetamine backbone, such as 2 MPA, 5-MAPB, and 6-MAPB, was N-demethylation, whereas for the three methyl-amphetamine isomers and CFA aromatic hydroxylation was the predominant step. 5 APB and 6-APB were metabolized only to a minor extent, resulting in the unchanged drug being the main target for urinalysis. The isoenzymes mainly involved in the N demethylation steps were CYP2B6, CYP2C19, CYP2D6, and CYP3A4, whereas the aromatic hydroxylations were catalyzed by CYP2D6 and CYP2C19. The intake of each tested compound could be proved within the established SUSAs, either with the unchanged drugs or the nor metabolites being the main targets in urine, or in the case of CFA and the three MAs, the hydroxy-aryl metabolites. Separation of isomers was successfully accomplished with an additional work-up, including heptafluorobutyrylation. For 5-MAPB, plasma concentrations determined in authentic cases were in the same range as published for MDMA.