Title
In vitro and in vivo human metabolism of the synthetic cannabinoid AB-CHMINACA In vitro and in vivo human metabolism of the synthetic cannabinoid AB-CHMINACA
Author
Faculty/Department
Faculty of Pharmaceutical, Biomedical and Veterinary Sciences. Pharmacy
Publication type
article
Publication
Subject
Chemistry
Biology
Pharmacology. Therapy
Source (journal)
Drug testing and analysis
Volume/pages
7(2015) :10 , p. 866-876
ISSN
1942-7603
ISI
000362691800002
Carrier
E
Target language
English (eng)
Full text (Publishers DOI)
Affiliation
University of Antwerp
Abstract
N-[(1S)-1-(aminocarbonyl)-2-methylpropyl]-1-(cyclohexylmethyl)-1H-indazole-3-carboxamide (AB-CHMINACA) is a recently introduced synthetic cannabinoid. At present, no information is available about in vitro or in vivo human metabolism of AB-CHMINACA. Therefore, biomonitoring studies to screen AB-CHMINACA consumption lack any information about the potential biomarkers (e.g. metabolites) to target. To bridge this gap, we investigated the in vitro metabolism of AB-CHMINACA using human liver microsomes (HLMs). Formation of AB-CHMINACA metabolites was monitored using liquid chromatography coupled to time-of-flight mass spectrometry. Twenty-six metabolites of AB-CHMINACA were detected including seven mono-hydroxylated and six di-hydroxylated metabolites and a metabolite resulting from N-dealkylation of AB-CHMINACA, all produced by cytochrome P450 (CYP) enzymes. Two carboxylated metabolites, likely produced by amidase enzymes, and five glucuronidated metabolites were also formed. Five mono-hydroxylated and one carboxylated metabolite were likely the major metabolites detected. The involvement of individual CYPs in the formation of AB-CHMINACA metabolites was tested using a panel of seven human recombinant CYPs (rCYPs). All the hydroxylated AB-CHMINACA metabolites produced by HLMs were also produced by the rCYPs tested, among which rCYP3A4 was the most active enzyme. Most of the in vitro metabolites of AB-CHMINACA were also present in urine obtained from an AB-CHMINACA user, therefore showing the reliability of the results obtained using the in vitro metabolism experiments conducted to predict AB-CHMINACA in vivo metabolism. The AB-CHMINACA metabolites to target in biomonitoring studies using urine samples are now reliably identified and can be used for routine analysis.
E-info
https://repository.uantwerpen.be/docman/iruaauth/3fa3c9/4b318724d07.pdf
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Full text (open access)
https://repository.uantwerpen.be/docman/irua/913c39/125032.pdf
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