Advances in urinary biomarker research of synthetic cannabinoids

New psychoactive substances (NPS) are chemical compounds designed to mimic the action of existing illicit recreational drugs. Synthetic cannabinoids (SCs) are a subclass of NPS which bind to the cannabinoid receptors, CB1 and CB2, and mimic the action of cannabis. SCs have dominated recent NPS seizure reports worldwide. While urine is the most common matrix for drug-of-abuse testing, SCs undergo extensive Phase I and Phase II metabolism, resulting in almost undetectable parent compounds in urine samples. Therefore, the major urinary metabolites of SCs are usually investigated as surrogate biomarkers to identify their consumption. Since seized urine samples after consuming novel SCs may be unavailable in a timely manner, human hepatocytes, human liver microsomes and human transporter overexpressed cell lines are physiologically-relevant in vitro systems for performing metabolite identification, metabolic stability, reaction phenotyping and transporter experiments to establish the disposition of SC and its metabolites. Coupling these in vitro experiments with in vivo verification using limited authentic urine samples, such a two-pronged approach has proven to be effective in establishing urinary metabolites as biomarkers for rapidly emerging SCs.