Metabolic characterization of AH-7921, a synthetic opioid designer drug: in vitro metabolic stability assessment and metabolite identification, evaluation of in silico prediction, and in vivo confirmation

Drug Testing and Analysis
Ariane WohlfarthMarilyn A Huestis

Abstract

AH-7921 (3,4-dichloro-N-[(1-dimethylamino)cyclohexylmethyl]benzamide) is a new synthetic opioid and has led to multiple non-fatal and fatal intoxications. To comprehensively study AH-7921 metabolism, we assessed human liver microsome (HLM) metabolic stability, determined AH-7921's metabolic profile after human hepatocytes incubation, confirmed our findings in a urine case specimen, and compared results to in silico predictions. For metabolic stability, 1 µmol/L AH-7921 was incubated with HLM for up to 1 h; for metabolite profiling, 10 µmol/L was incubated with pooled human hepatocytes for up to 3 h. Hepatocyte samples were analyzed by liquid chromatography quadrupole/time-of-flight high-resolution mass spectrometry (MS). High-resolution full scan MS and information-dependent acquisition MS/MS data were analyzed with MetabolitePilot™ (SCIEX) using multiple data processing algorithms. The presence of AH-7921 and metabolites was confirmed in the urine case specimen. In silico prediction of metabolite structures was performed with MetaSite™ (Molecular Discovery). AH-7921 in vitro half-life was 13.5 ± 0.4 min. We identified 12 AH-7921 metabolites after hepatocyte incubation, predominantly generated by demethylation, less dominantly ...Continue Reading

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Citations

Jan 27, 2016·The AAPS Journal·Xingxing DiaoMarilyn A Huestis
Jul 3, 2016·Archives of Toxicology·H H Maurer, Markus R Meyer
Jul 6, 2018·Frontiers in Pharmacology·Renata SoliminiRaffaele Giorgetti
Oct 27, 2018·Frontiers in Pharmacology·Clara Pérez-MañáMagi Farré
Jul 16, 2019·Forensic Sciences Research·Inês TabarraEugenia Gallardo
Nov 13, 2018·Frontiers in Pharmacology·Marta ConcheiroGail Cooper
Jan 1, 2021·International Journal of Molecular Sciences·Jeremy CarlierMarilyn A Huestis
Sep 16, 2018·Neuroscience and Biobehavioral Reviews·Laurent KarilaAmine Benyamina

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