In Vitro Metabolic Study of Four Synthetic Cathinones: 4-MPD, 2-NMC, 4F-PHP and bk-EPDP

The use of illicit drugs is exceedingly prevalent in society, and several of them can be illegally purchased from the internet. This occurrence is particularly augmented by the rapid emergence of novel psychoactive substances (NPS), which are sold and distributed as "legal highs". Amongst NPS, the class of synthetic cathinones represents stimulant substances exhibiting similar effects to amphetamine and its derivatives. Despite potentially being less psychoactive than amphetamine, synthetic cathinones are harmful substances for humans, and little or no information is available regarding their pharmacology and toxicology. The present study investigated the in vitro metabolism and metabolites of four recent synthetic cathinones, namely, 1-(4-methylphenyl)-2-(methylamino)-pentanone (4-MPD), 1-(4-methylphenyl)-2-dimethylamino-propanone (2-NMC), 1-(4-fluorophenyl)-2-(pyrrolidin-1-yl-hexanone (4F-PHP) and 1-(1,3-benzodioxol-5-yl)-2-(ethylamino)-1-pentanone (bk-EPDP). Our in vitro metabolism study resulted in 24 identified metabolites, including both phase I and phase II metabolites. All metabolites were detected and identified using liquid chromatography-high-resolution mass spectrometry and may serve as additional markers of abuse of these NPS in toxicological analyses.