Simulation of the Metabolism of New Psychoactive Substances Using Electrochemistry‐Mass Spectrometry: Introducing an Innovative Software Tool for Rapid Data Evaluation

An innovative software tool for the rapid and efficient simulation of the metabolism of new psychoactive substances (NPS) was developed, based on the open-source project mzmine, and applied. NPS are compounds designed to mimic the psychotropic effects of established illicit drugs while circumventing drug legislation. These compounds are developed solely regarding their desired effects, thus possibly leading to harmful side effects including the formation of toxic metabolites. Analytical reference standards, needed to carry out metabolic studies, are not immediately available because emerging NPS are primarily discovered subsequent to drug confiscations. Using these confiscated substances in traditional metabolic in vivo or in vitro studies is often not possible due to the substances being impure or being a part of a mixture of different NPS. Therefore, a software tool was developed to streamline the evaluation of data acquired by the online combination of electrochemistry and mass spectrometry for the simulation of NPS metabolism. Using this tool, it is possible to generate mass voltammograms directly from mass spectrometric raw data. Combining this newly implemented tool with existing filtering algorithms in mzmine, we simulated the metabolism of the synthetic cannabinoid receptor agonist (SCRA) methyl 3,3-dimethyl-2-[1-(pent-4-en-1-yl)-1H-indazole-3-carboxamido] butanoate (MDMB-4en-PINACA) from a mixed solution of different NPS. Fragmentation data indicated that one of the transformation products found for MDMB-4en-PINACA is likely of a quinoid structure. The potential formation of this possibly highly reactive quinoid metabolite could be a first hint for possible causes of adverse side effects frequently reported after the recreational use of MDMB-4en-PINACA and related SCRAs.