Title :

Metabolite elucidation of 2-fluoro-deschloroketamine (2f-dck) using molecular networking across three complementary in vitro and in vivo models

Author(s) :

Gicquel, Thomas [Auteur]
Centre Hospitalier Universitaire [Rennes]
Nutrition, Métabolismes et Cancer [NuMeCan]
Pelletier, Romain [Auteur]
Centre Hospitalier Universitaire [Rennes]
Richeval, Camille [Auteur]
IMPact de l'Environnement Chimique sur la Santé humaine (IMPECS) - ULR 4483
Gish, Alexandr [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Toxicologie et Génopathies [CHRU Lille]
Hakim, Florian [Auteur]
Impact de l'environnement chimique sur la santé humaine - ULR 4483 [IMPECS]
Ferron, Pierre-Jean [Auteur]
Nutrition, Métabolismes et Cancer [NuMeCan]
Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou]
Mesli, Vadim [Auteur]
Unité de Taphonomie Médico-Légale (UTML) - ULR 7367
Allorge, Delphine [Auteur]
IMPact de l'Environnement Chimique sur la Santé humaine (IMPECS) - ULR 4483
Morel, Isabelle [Auteur]
Nutrition, Métabolismes et Cancer [NuMeCan]
Gaulier, Jean-Michel [Auteur]
IMPact de l'Environnement Chimique sur la Santé humaine (IMPECS) - ULR 4483

Journal title :

Drug testing and analysis

Abbreviated title :

Drug Test Anal

Volume number :

14

Pages :

1-196

Publisher :

Wiley

Publication date :

2021-09-13

ISSN :

1942-7611

English keyword(s) :

2F-DCK
HepaRG cell line
metabolism
molecular networking
new psychoactive substances

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

This work first aims to investigate metabolites of 2-fluoro-deschloroketamine (2F-DCK), a new arylcyclohexylamine derivatives (a group of dissociative ketamine-based substances) using two in vitro experimental approaches, ...
Show more >This work first aims to investigate metabolites of 2-fluoro-deschloroketamine (2F-DCK), a new arylcyclohexylamine derivatives (a group of dissociative ketamine-based substances) using two in vitro experimental approaches, and to compare obtained results by means of molecular networking. Metabolites of 2F-DCK were investigated using both human liver microsomes (HLMs) and hepatic (HepaRG) cell line incubates using molecular networking approach: 2F-DCK pure substance was incubated with HLMs for up to 1 h at two concentrations (100 and 500 μM) and with HepaRG cells for two time periods (8 and 24 h) at one concentration (20 μM). In vitro obtained results were subsequently applied to a 2F-DCK-related fatality case. In vitro-produced metabolites were investigated using high-resolution accurate mass spectrometry using Orbitrap mass analyzer technology. Thirteen metabolites were in vitro produced and several metabolic pathways can be postulated. Seven additional metabolites were found in post-mortem samples (bile and urine) of the case, comprising three Phase II metabolites, which appear to be minor in vivo metabolites. HLMs and HepaRG cell models appear to be complementary and obtained data allowed the identification of several specific 2F-DCK metabolites in biological samples. In practical terms, observed metabolic ratios suggested that nor-2F-DCK (208.1137 m/z) and a hydrogenated metabolite (224.1443 m/z) could be proposed as reliable metabolites to be recorded in HRMS libraries in order to improve detection of 2F-DCK use.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

CHU Lille
Institut Pasteur de Lille
Université de Lille

Collections :

• IMPact de l'Environnement Chimique sur la Santé humaine (IMPECS) - ULR 4483
• Unité de Taphonomie Médico-Légale & d’Anatomie (UTMLA) - ULR 7367

Submission date :

2022-02-02T10:25:03Z
2024-02-15T08:32:00Z
2024-02-23T14:10:18Z