Comparative analysis of the in vitro biotransformation of the synthetic cannabinoid CHO-4'Me-5'Br-FUBOXPYRA using liver microsomes

Abstract

New Psychoactive Substances (NPS) are compounds of synthetic origin capable of mimicking the effects of traditional drugs of abuse. This group of substances is not included in the 1961 Single Convention on Narcotic Drugs and the 1971 Convention on Psychotropic Substances. The high number of NSP discovered annually represents a warning for global public health, since the toxicological and metabolic properties of many of these substances are still poorly understood, which makes clinical management in cases of poisoning difficult. CHO-4'Me-5'Br-FUBOXPYRA is an NPS from the synthetic cannabinoid class, which has a possible mechanism of action via allosteric modulation of CB2 receptors. Seizures of this substance have been reported in some countries on the European continent, however there is still no article describing its pharmacological, toxicological and metabolic properties. In vitro models using liver microsomes are commonly used to characterize the metabolic profile of drugs and drugs of abuse, as they are low cost and allow extrapolations aimed at understanding in vivo metabolism. The objective of this study is to compare the metabolic profiles of the synthetic cannabinoid CHO-4'Me-5'Br-FUBOXPYRA using liver microsomes through a multi-species approach (rat, mouse and human), in addition to elucidating its metabolites through liquid chromatography coupled to high resolution mass spectrometry (LC-HRMS).