In Vitro Metabolic Fate of the Synthetic Cannabinoid Receptor Agonists QMPSB and QMPCB (SGT-11) Including Isozyme Mapping and Esterase Activity

Quinolin-8-yl 4-methyl-3-(piperidine-1-sulfonyl)benzoate (QMPSB) and quinolin-8-yl 4-methyl-3-(piperidine-1-carbonyl)benzoate (QMPCB, SGT-11) are synthetic cannabinoid receptor agonists (SCRAs). Knowing their metabolic fate is crucial for the identification of toxicological screening targets to predict possible drug interactions. The presented study aimed identify in vitro phase I/II metabolites QMPSB QMPCB contribution different monooxygenases human carboxylesterases by using pooled liver S9 fraction (pHLS9), recombinant monooxygenases, three carboxylesterases, microsomes. Analyses were carried out liquid chromatography high-resolution tandem mass spectrometry. showed ester hydrolysis, hydroxy carboxylic acid products detected both cases. Mono/dihydroxy formed, as corresponding glucuronides sulfates. Most could be positive ionization mode with exception some metabolites, which only found negative mode. Monooxygenase activity revealed that CYP2B6/CYP2C8/CYP2C9/CYP2C19/CYP3A4/CYP3A5 involved hydroxylations. Esterase involvement all investigated isoforms. Additionally, extensive non-enzymatic hydrolysis was observed. Considering results experiments, inclusion monohydroxy into procedures recommended.