In Vitro Metabolite Profiling of ADB-FUBINACA, A New Synthetic Cannabinoid
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作者:
Carlier, Jeremy
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NIDA, Chem & Drug Metab, IRP, NIH, Baltimore, MD 21224 USANIDA, Chem & Drug Metab, IRP, NIH, Baltimore, MD 21224 USA
Carlier, Jeremy
[1
]
Diao, Xingxing
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NIDA, Chem & Drug Metab, IRP, NIH, Baltimore, MD 21224 USANIDA, Chem & Drug Metab, IRP, NIH, Baltimore, MD 21224 USA
Diao, Xingxing
[1
]
Wohlfarth, Ariane
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NIDA, Chem & Drug Metab, IRP, NIH, Baltimore, MD 21224 USA
Natl Board Forens Med, Linkoping, Sweden
Linkoping Univ, Div Drug Res, Dept Med & Hlth Sci, Linkoping, SwedenNIDA, Chem & Drug Metab, IRP, NIH, Baltimore, MD 21224 USA
Wohlfarth, Ariane
[1
,2
,3
]
Scheidweiler, Karl
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NIDA, Chem & Drug Metab, IRP, NIH, Baltimore, MD 21224 USANIDA, Chem & Drug Metab, IRP, NIH, Baltimore, MD 21224 USA
Scheidweiler, Karl
[1
]
Huestis, Marilyn A.
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NIDA, Chem & Drug Metab, IRP, NIH, Baltimore, MD 21224 USA
Univ Maryland, Sch Med, Baltimore, MD 21201 USANIDA, Chem & Drug Metab, IRP, NIH, Baltimore, MD 21224 USA
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
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.
机构:
Ctr Dis Control, Natl Ctr Environm Hlth, Off Environm Hlth Emergencies, Atlanta, GA 30333 USACtr Dis Control, Natl Ctr Environm Hlth, Off Environm Hlth Emergencies, Atlanta, GA 30333 USA
Schwartz, Michael D.
;
Trecki, Jordan
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Drug Enforcement Adm, Off Divers Control, Drug & Chem Evaluat Sect, Springfield, VA USACtr Dis Control, Natl Ctr Environm Hlth, Off Environm Hlth Emergencies, Atlanta, GA 30333 USA
Trecki, Jordan
;
Edison, Laura A.
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Ctr Dis Control & Prevent, Epidemiol Program Off, Atlanta, GA USACtr Dis Control, Natl Ctr Environm Hlth, Off Environm Hlth Emergencies, Atlanta, GA 30333 USA
Edison, Laura A.
;
Steck, Alaina R.
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Georgia Poison Ctr, Atlanta, GA USACtr Dis Control, Natl Ctr Environm Hlth, Off Environm Hlth Emergencies, Atlanta, GA 30333 USA
Steck, Alaina R.
;
Arnold, Justin K.
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Georgia Poison Ctr, Atlanta, GA USACtr Dis Control, Natl Ctr Environm Hlth, Off Environm Hlth Emergencies, Atlanta, GA 30333 USA
Arnold, Justin K.
;
Gerona, Roy R.
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机构:
Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USACtr Dis Control, Natl Ctr Environm Hlth, Off Environm Hlth Emergencies, Atlanta, GA 30333 USA
机构:
Ctr Dis Control, Natl Ctr Environm Hlth, Off Environm Hlth Emergencies, Atlanta, GA 30333 USACtr Dis Control, Natl Ctr Environm Hlth, Off Environm Hlth Emergencies, Atlanta, GA 30333 USA
Schwartz, Michael D.
;
Trecki, Jordan
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h-index: 0
机构:
Drug Enforcement Adm, Off Divers Control, Drug & Chem Evaluat Sect, Springfield, VA USACtr Dis Control, Natl Ctr Environm Hlth, Off Environm Hlth Emergencies, Atlanta, GA 30333 USA
Trecki, Jordan
;
Edison, Laura A.
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机构:
Ctr Dis Control & Prevent, Epidemiol Program Off, Atlanta, GA USACtr Dis Control, Natl Ctr Environm Hlth, Off Environm Hlth Emergencies, Atlanta, GA 30333 USA
Edison, Laura A.
;
Steck, Alaina R.
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机构:
Georgia Poison Ctr, Atlanta, GA USACtr Dis Control, Natl Ctr Environm Hlth, Off Environm Hlth Emergencies, Atlanta, GA 30333 USA
Steck, Alaina R.
;
Arnold, Justin K.
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机构:
Georgia Poison Ctr, Atlanta, GA USACtr Dis Control, Natl Ctr Environm Hlth, Off Environm Hlth Emergencies, Atlanta, GA 30333 USA
Arnold, Justin K.
;
Gerona, Roy R.
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机构:
Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USACtr Dis Control, Natl Ctr Environm Hlth, Off Environm Hlth Emergencies, Atlanta, GA 30333 USA