Detection of Metabolites of the New Synthetic Cannabinoid MDMB-4en-PINACA in Human Urine by Liquid and Gas Chromatography–Mass Spectrometry

Abstract

MDMB-4en-PINACA is a new synthetic psychoactive compound that has been widely distributed in Russia since at least 2020 and has high activity against the human cannabinoid receptor CB1. Its distinctive feature is the presence of an N-pentene residue, which is rare for this group of compounds. The significant hydrophobicity of MDMB-4en-PINACA, like most other synthetic cannabimimetics distributed on the world markets, causes almost complete biotransformation of the original compound and its extremely low content in urine. Hence, it follows that its metabolites should be identified, the detection of which would indicate the use of MDMB-4en-PINACA. To solve this problem, gas and liquid chromatography–mass spectrometry analysis was used, including high-performance chromatography–mass spectrometry with a quadrupole time-of-flight detector and a three-dimensional ion trap detector equipped with an electrospray ionization source. A number of putative metabolites of MDMB-4en-PINACA were detected in human urine, which were identified as products of hydrolysis, mono- and dihydroxylation, reduction, dihydrodiol formation, carboxylation, carboxylation with elimination of the methylene group, N-dealkylation, and combinations of these processes. A number of metabolites were found in the form of glucuronides. The results obtained are in good agreement with published data. The search for the products of hydrolysis, dihydroxylation, and dihydrodiol formation is optimal for routine chemical toxicological and forensic chemical analysis of urine by gas chromatography-mass spectrometry, while it is also recommended to detect glucuronides of hydrolysis products and dihydrodiol formation with the use of liquid chromatography–mass spectrometry.