Urinary Metabolite Biomarkers for the Detection of Synthetic Cannabinoid ADB-BUTINACA Abuse.
Clin Chem
; 67(11): 1534-1544, 2021 11 01.
Article
em En
| MEDLINE
| ID: mdl-34387654
ABSTRACT
BACKGROUND:
(S)-N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-butyl-1H-indazole-3carboxamide (ADB-BUTINACA) is an emerging synthetic cannabinoid that was first identified in Europe in 2019 and entered Singapore's drug scene in January 2020. Due to the unavailable toxicological and metabolic data, there is a need to establish urinary metabolite biomarkers for detection of ADB-BUTINACA consumption and elucidate its biotransformation pathways for rationalizing its toxicological implications.METHODS:
We characterized the metabolites of ADB-BUTINACA in human liver microsomes using liquid chromatography Orbitrap mass spectrometry analysis. Enzyme-specific inhibitors and recombinant enzymes were adopted for the reaction phenotyping of ADB-BUTINACA. We further used recombinant enzymes to generate a pool of key metabolites in situ and determined their metabolic stability. By coupling in vitro metabolism and authentic urine analyses, a panel of urinary metabolite biomarkers of ADB-BUTINACA was curated.RESULTS:
Fifteen metabolites of ADB-BUTINACA were identified with key biotransformations being hydroxylation, N-debutylation, dihydrodiol formation, and oxidative deamination. Reaction phenotyping established that ADB-BUTINACA was rapidly eliminated via CYP2C19-, CYP3A4-, and CYP3A5-mediated metabolism. Three major monohydroxylated metabolites (M6, M12, and M14) were generated in situ, which demonstrated greater metabolic stability compared to ADB-BUTINACA. Coupling metabolite profiling with urinary analysis, we identified four urinary biomarker metabolites of ADB-BUTINACA 3 hydroxylated metabolites (M6, M11, and M14) and 1 oxidative deaminated metabolite (M15).CONCLUSIONS:
Our data support a panel of four urinary metabolite biomarkers for diagnosing the consumption of ADB-BUTINACA.Palavras-chave
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Canabinoides
/
Transtornos Relacionados ao Uso de Substâncias
Tipo de estudo:
Diagnostic_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article