Structure-metabolism relationships of valine and ferf-leucine-derived synthetic cannabinoid receptor agonists: a systematic comparison of the in vitro phase I metabolism using pooled human liver microsomes and high-resolution mass spectrometry

摘要

Purpose Synthetic cannabinoid receptor agonists, commonly referred to as 'synthetic cannabinoids' (SCs), gained popularity as recreational drugs due to their cannabis-like effects. The subclass of valine or tert-leucine-derived SCs has dominated the 'designer drug' market in recent years and has been associated with several severe intoxication cases. Most SCs are highly lipophilic compounds and are extensively metabolized prior to renal excretion. Hence, for drug detection in urine samples, the major metabolites of new compounds have to be identified first. The aim of this study was to elucidate structure-metabolism relationships (SMRs) of valine and tert-leucine-derived SCs enabling in-depth understanding of their phase I biotransforma-tion and facilitating the prediction of suitable analytical targets for urine analysis.