Urinary Metabolite Biomarkers for the Detection of Synthetic Cannabinoid ADB-BUTINACA Abuse
| Autor: | Chi Hon Sia, Evelyn Mei Ling Goh, Yen Li Tan, Eric Chun Yong Chan, Hooi Yan Moy, Ching Yee Fong, Ziteng Wang |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
chemistry.chemical_classification
Psychotropic Drugs CYP3A4 Cannabinoids Substance-Related Disorders Metabolite medicine.medical_treatment Biochemistry (medical) Clinical Biochemistry Oxidative deamination Orbitrap law.invention Hydroxylation chemistry.chemical_compound Enzyme chemistry Biotransformation Biochemistry law Microsomes Liver medicine Humans Cannabinoid Biomarkers Chromatography Liquid |
| Zdroj: | Clinical Chemistry. 67:1534-1544 |
| ISSN: | 1530-8561 0009-9147 |
| DOI: | 10.1093/clinchem/hvab134 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|