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In Vitro Metabolite Profiling of ADB-FUBINACA, A New Synthetic Cannabinoid

[ Vol. 15 , Issue. 5 ]

Author(s):

Jeremy Carlier, Xingxing Diao, Ariane Wohlfarth, Karl Scheidweiler and Marilyn A. Huestis   Pages 682 - 691 ( 10 )

Abstract:


Background: Metabolite profiling of novel psychoactive substances (NPS) is critical for documenting drug consumption. N-(1-amino-3,3-dimethyl-1-oxobutan-2-yl)-1-(4-fluorobenzyl)-1Hindazole- 3-carboxamide (ADB-FUBINACA) is an emerging synthetic cannabinoid whose toxicological and metabolic data are currently unavailable.

Methods: We aimed to determine optimal markers for identifying ADB-FUBINACA intake. Metabolic stability was evaluated with human liver microsome incubations. Metabolites were identified after 1 and 3 h incubation with pooled human hepatocytes, liquid chromatography- high resolution mass spectrometry in positive-ion mode (5600+ TripleTOF®, Sciex) and several data mining approaches (MetabolitePilot™, Sciex).

Results: Metabolite separation was achieved on an Ultra Biphenyl column (Restek®); full-scan TOFMS and information-dependent acquisition MS/MS data were acquired. ADB-FUBINACA microsomal half-life was 39.7 min, with a predicted hepatic clearance of 9.0 mL/min/kg and a 0.5 extraction ratio (intermediate-clearance drug). Twenty-three metabolites were identified. Major metabolic pathways were alkyl and indazole hydroxylation, terminal amide hydrolysis, subsequent glucuronide conjugations, and dehydrogenation.

Conclusion: We recommend ADB-FUBINACA hydroxyalkyl, hydroxydehydroalkyl and hydroxylindazole metabolites as ADB-FUBINACA intake markers. N-dealkylated metabolites are not specific ADB-FUBINACA metabolites and should not be used as definitive markers of consumption. This is the first ADB-FUBINACA in vitro metabolism study; in vivo experiments enabling pharmacokinetic and pharmacodynamics studies or urine from authentic clinical/forensic cases are needed to confirm our results.

Keywords:

ADB-FUBINACA, synthetic cannabinoid, novel psychoactive substances, metabolism, hepatocytes, LC-HRMS

Affiliation:

Chemistry and Drug Metabolism, IRP, National Institute on Drug Abuse, NIH, Baltimore, MD 21224, aChemistry and Drug Metabolism, IRP, National Institute on Drug Abuse, NIH, Baltimore, MD 21224, Chemistry and Drug Metabolism, IRP, National Institute on Drug Abuse, NIH, Baltimore, MD 21224, Chemistry and Drug Metabolism, IRP, National Institute on Drug Abuse, NIH, Baltimore, MD 21224, Chemistry and Drug Metabolism, IRP, National Institute on Drug Abuse, NIH, Baltimore, MD 21224

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