@article{ref1,
title="In vitro and in vivo human metabolism of the synthetic cannabinoid AB-CHMINACA",
journal="Drug testing and analysis",
year="2015",
author="Erratico, Claudio and Negreira, Noelia and Norouzizadeh, Helia and Covaci, Adrian and Neels, Hugo and Maudens, Kristof and van Nuijs, Alexander L. N.",
volume="7",
number="10",
pages="866-876",
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. Copyright © 2015 John Wiley & Sons, Ltd.<p /> <p>Language: en</p>",
language="en",
issn="1942-7603",
doi="10.1002/dta.1796",
url="http://dx.doi.org/10.1002/dta.1796"
}