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In vitro metabolic fate of the synthetic cannabinoid receptor agonists 2F-QMPSB and SGT-233 including isozyme mapping and carboxylesterases activity testing

Richter, MJ, Wagmann, L, Brandt, SD and Meyer, MR (2022) In vitro metabolic fate of the synthetic cannabinoid receptor agonists 2F-QMPSB and SGT-233 including isozyme mapping and carboxylesterases activity testing. Journal of Analytical Toxicology. ISSN 0146-4760

2F-QMPSB SGT-233_JAT_accepted.pdf - Accepted Version

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2F-QMPSB (quinolin-8-yl 3-(4,4-difluoropiperidine-1-sulfonyl)-4-methylbenzoate) and SGT-233 (3-(4,4-difluoropiperidine-1-sulfonyl)-4-methyl-N-(2-phenylpropan-2-yl)benzamide) belong to a new group of synthetic cannabinoid receptor agonists (SCRAs) containing a sulfamoyl benzoate or sulfamoyl benzamide core structure. 2F-QMPSB was identified on herbal material seized in Europe in 2018. The aims of the presented study were the identification of in vitro phase I and II metabolites of 2F-QMPSB and SGT-233 to find analytical targets for toxicological screenings. Furthermore, the contribution of different monooxygenases and human carboxylesterases to phase I metabolism was investigated. Liquid chromatography coupled to high-resolution tandem mass spectrometry was used for analysis. Ester hydrolysis was found to be an important step in the metabolism of 2F-QMPSB, which was catalyzed mainly by hCES1 isoforms. Additionally, non-enzymatic ester hydrolysis was observed in case of 2F-QMPSB. Notably, the carboxylic acid product derived from ester hydrolysis and metabolites thereof were only detectable in negative ionization mode. In case of SGT-233, mono- and dihydroxy metabolites were identified, as well as glucuronides. CYP2C8, CYP2C9, CYP2C19, CYP3A4, and CYP3A5 were found to be involved in the hydroxylation of both compounds. The results of these in vitro experiments suggest that the ester hydrolysis products of 2F-QMPSB and their glucuronides are suitable targets for toxicological screenings. In the case of SGT-233, the mono- and dihydroxy metabolites were identified as suitable screening targets. The involvement of various CYP isoforms in the metabolism of both substances reduces the likelihood of drug-drug interactions due to CYP inhibition.

Item Type: Article
Additional Information: The version of record Matthias J Richter, Lea Wagmann, Simon D Brandt, Markus R Meyer, In Vitro Metabolic Fate of the Synthetic Cannabinoid Receptor Agonists 2F-QMPSB and SGT-233 Including Isozyme Mapping and Carboxylesterases Activity Testing, Journal of Analytical Toxicology, 2022;, bkac072, is available online at: https://doi.org/10.1093/jat/bkac072
Uncontrolled Keywords: 0301 Analytical Chemistry; 1115 Pharmacology and Pharmaceutical Sciences; Analytical Chemistry
Subjects: R Medicine > RA Public aspects of medicine > RA0421 Public health. Hygiene. Preventive Medicine
R Medicine > RA Public aspects of medicine > RA1190 Toxicology. Poisions
R Medicine > RM Therapeutics. Pharmacology
R Medicine > RS Pharmacy and materia medica
Divisions: Pharmacy & Biomolecular Sciences
Publisher: Oxford University Press
SWORD Depositor: A Symplectic
Date Deposited: 23 Aug 2022 10:59
Last Modified: 09 Sep 2023 00:50
DOI or ID number: 10.1093/jat/bkac072
URI: https://researchonline.ljmu.ac.uk/id/eprint/17436
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