|
Title
|
|
|
|
In vitro and in vivo human metabolism of the synthetic cannabinoid AB-CHMINACA
|
|
|
Author
|
|
|
|
|
|
|
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. |
|
|
|
Language
|
|
|
|
English
|
|
|
Source (journal)
|
|
|
|
Drug testing and analysis. - -
|
|
|
Publication
|
|
|
|
2015
|
|
|
ISSN
|
|
|
|
1942-7603
[print]
1942-7611
[online]
|
|
|
DOI
|
|
|
|
10.1002/DTA.1796
|
|
|
Volume/pages
|
|
|
|
7
:10
(2015)
, p. 866-876
|
|
|
ISI
|
|
|
|
000362691800002
|
|
|
Pubmed ID
|
|
|
|
25865117
|
|
|
Full text (Publisher's DOI)
|
|
|
|
|
|
|
Full text (open access)
|
|
|
|
|
|
|
Full text (publisher's version - intranet only)
|
|
|
|
|
|