Identification of MT-45 metabolites: in silico prediction, in vitro incubation with rat hepatocytes and in vivo confirmation
MT-45 is a synthetic opioid with a pharmacological activity comparable to morphine and it has been involved in intoxications and fatalities reported in Europe and in USA. It was recently subject to control measures, but to date the metabolic pathways of the substance are still unknown. Using rat hepatocytes and LC-HRMS, 14 novel Phase I and II MT-45 metabolites were identified, products of monohydroxylation, dihydroxylation and N-dealkylation; glucuronide conjugation of mono- and dihydroxylated metabolites also occurred. The detected metabolites were firstly predicted in silico, then incubation of the drug with rat hepatocytes was carried out and the obtained metabolites were identified by LC-HRMS, with retention times, mass shift between theoretical mass and observed mass (