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Article

Phase I In Vitro Metabolic Profiling of the Synthetic Cannabinoid Receptor Agonists CUMYL-THPINACA and ADAMANTYL-THPINACA

Institute of Forensic Medicine, Department of Biomedical Engineering, University of Basel, 4056 Basel, Switzerland
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Author to whom correspondence should be addressed.
Academic Editor: Cornelius Hess
Metabolites 2021, 11(8), 470; https://doi.org/10.3390/metabo11080470
Received: 18 June 2021 / Revised: 16 July 2021 / Accepted: 16 July 2021 / Published: 21 July 2021
(This article belongs to the Special Issue Metabolite Analysis in Forensic Toxicology)
Synthetic cannabinoid receptor agonists (SCRAs) remain popular drugs of abuse. As many SCRAs are known to be mostly metabolized, in vitro phase I metabolic profiling was conducted of the two indazole-3-carboxamide SCRAs: CUMYL-THPINACA and ADAMANTYL-THPINACA. Both compounds were incubated using pooled human liver microsomes. The sample clean-up consisted of solid phase extraction, followed by analysis using liquid chromatography coupled to a high resolution mass spectrometer. In silico-assisted metabolite identification and structure elucidation with the data-mining software Compound Discoverer was applied. Overall, 28 metabolites were detected for CUMYL-THPINACA and 13 metabolites for ADAMATYL-THPINACA. Various mono-, di-, and tri-hydroxylated metabolites were detected. For each SCRA, an abundant and characteristic di-hydroxylated metabolite was identified as a possible in vivo biomarker for screening methods. Metabolizing cytochrome P450 isoenzymes were investigated via incubation of relevant recombinant liver enzymes. The involvement of mainly CYP3A4 and CYP3A5 in the metabolism of both substances were noted, and for CUMYL-THPINACA the additional involvement (to a lesser extent) of CYP2C8, CYP2C9, and CYP2C19 was observed. The results suggest that ADAMANTYL-THPINACA might be more prone to metabolic drug−drug interactions than CUMYL-THPINACA, when co-administrated with strong CYP3A4 inhibitors. View Full-Text
Keywords: synthetic cannabinoid receptor agonists; in vitro metabolism; high resolution mass spectrometry; Compound Discoverer synthetic cannabinoid receptor agonists; in vitro metabolism; high resolution mass spectrometry; Compound Discoverer
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MDPI and ACS Style

Monti, M.C.; Scheurer, E.; Mercer-Chalmers-Bender, K. Phase I In Vitro Metabolic Profiling of the Synthetic Cannabinoid Receptor Agonists CUMYL-THPINACA and ADAMANTYL-THPINACA. Metabolites 2021, 11, 470. https://doi.org/10.3390/metabo11080470

AMA Style

Monti MC, Scheurer E, Mercer-Chalmers-Bender K. Phase I In Vitro Metabolic Profiling of the Synthetic Cannabinoid Receptor Agonists CUMYL-THPINACA and ADAMANTYL-THPINACA. Metabolites. 2021; 11(8):470. https://doi.org/10.3390/metabo11080470

Chicago/Turabian Style

Monti, Manuela C., Eva Scheurer, and Katja Mercer-Chalmers-Bender. 2021. "Phase I In Vitro Metabolic Profiling of the Synthetic Cannabinoid Receptor Agonists CUMYL-THPINACA and ADAMANTYL-THPINACA" Metabolites 11, no. 8: 470. https://doi.org/10.3390/metabo11080470

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