Elucidation of the biotrasformation pathways of new designer drugs by chromatography-mass spectrometry following in vitro metabolism studies

Besides the amphetamine-type designer drugs, which have been widely abused for decades, recently a number of new psychoactive substances (i.e. cannabimimetics, b-keto amphetamines and 2,5-dimethoxy amphetamines, 2,5- phenylamines, b-keto amphetamines, phencyclidines, piperazines, pyrrolidinophenones, fentanyls, piperidines, and tryptamine derivatives) have been made available on the illicit drug market [1-6]. The continual emergence and rapid diffusion of those compounds not only pose a serious health risk to consumers due to the scarce toxicological information available, but also present ongoing challenges to forensic laboratories, mainly due to the lack of both reference materials and pharmacokinetic data. The characterization of their metabolic profile and the parallel development of analytical procedures to detect their presence in biological samples are necessarily to activate the most appropriate policies to control their misuse [6-9]. This applies to different fields of analytical toxicology, including anti-doping analysis. Here, analytical approaches (based on the use of data dependent scan functions and high-resolution high-accuracy mass spectrometry) specifically developed to gain both molecular weight information and structural details of unknown analytes are proposed. These analytical strategies were used to select the most appropriate “marker(s)” (metabolite(s) and/or parent compound) to efficacy detect the abuse of b-keto amphetamines and 25 NBOMe derivatives following in silico and in vitro studies and to develop a target screening procedure.