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

被引:47
作者
Carlier, Jeremy [1 ]
Diao, Xingxing [1 ]
Wohlfarth, Ariane [1 ,2 ,3 ]
Scheidweiler, Karl [1 ]
Huestis, Marilyn A. [1 ,4 ]
机构
[1] NIDA, Chem & Drug Metab, IRP, NIH, Baltimore, MD 21224 USA
[2] Natl Board Forens Med, Linkoping, Sweden
[3] Linkoping Univ, Div Drug Res, Dept Med & Hlth Sci, Linkoping, Sweden
[4] Univ Maryland, Sch Med, Baltimore, MD 21201 USA
基金
美国国家卫生研究院;
关键词
ADB-FUBINACA; synthetic cannabinoid; novel psychoactive substances; metabolism; hepatocytes; LC-HRMS; AB-PINACA; URINARY METABOLITES; HUMAN HEPATOCYTES; ALPHA-PVT; DRUG; VIVO; AM-2201; JWH-018; UR-144;
D O I
10.2174/1570159X15666161108123419
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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)-1-Hindazole-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 (R), Sciex) and several data mining approaches (MetabolitePilot (TM), Sciex). Results: Metabolite separation was achieved on an Ultra Biphenyl column (Restek (R)); 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. 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.
引用
收藏
页码:682 / 691
页数:10
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