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

Content Provider	Europe PMC
Author	Carlier, Jeremy Diao, Xingxing Wohlfarth, Ariane Scheidweiler, Karl Huestis, Marilyn A.
Copyright Year	2017
Abstract	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)-1H-indazole-3-carboxamide (ADB-FUBINACA) is an emerging synthetic cannabinoid whose toxicological and metabolic data are currently unavailable. 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). Metabolite separation was achieved on an Ultra Biphenyl column (Restek®); full-scan TOF-MS 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. 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.
ISSN	1570159X
Journal	Current Neuropharmacology
Volume Number	15
PubMed Central reference number	PMC5771045
Issue Number	5
PubMed reference number	29403341
e-ISSN	18756190
DOI	10.2174/1570159X15666161108123419
Language	English
Publisher	Bentham Science Publishers
Publisher Date	2017-07-01
Access Restriction	Open
Rights License	This is an open access article licensed under the terms of the Creative Commons Attribution-Non-Commercial 4.0 International Public License (CC BY-NC 4.0) (https://creativecommons.org/licenses/by-nc/4.0/legalcode), which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited. © 2017 Bentham Science Publishers
Subject Keyword	ADB-FUBINACA synthetic cannabinoid novel psychoactive substances metabolism hepatocytes LC-HRMS
Content Type	Text
Resource Type	Article
Subject	Neurology Neurology (clinical) Pharmacology Pharmacology (medical) Psychiatry and Mental Health