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In Vitro Metabolite...
In Vitro Metabolite Profiling of ADB-FUBINACA, A New Synthetic Cannabinoid
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- Carlier, Jeremy (författare)
- NIDA, MD 21224 USA
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- Diao, Xingxing (författare)
- NIDA, MD 21224 USA
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- Wohlfarth, Ariane (författare)
- Linköpings universitet,Avdelningen för läkemedelsforskning,Medicinska fakulteten,NIDA, MD 21224 USA; National Board Forens Med, Linkoping, Sweden
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- Scheidweiler, Karl (författare)
- NIDA, MD 21224 USA
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- Huestis, Marilyn A. (författare)
- NIDA, MD 21224 USA; University of Maryland, MD 21201 USA
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(creator_code:org_t)
- BENTHAM SCIENCE PUBL LTD, 2017
- 2017
- Engelska.
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Ingår i: Current Neuropharmacology. - : BENTHAM SCIENCE PUBL LTD. - 1570-159X .- 1875-6190. ; 15:5, s. 682-691
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.2...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Nyckelord
- ADB-FUBINACA; synthetic cannabinoid; novel psychoactive substances; metabolism; hepatocytes; LC-HRMS
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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