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 correspondant]
Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou]
Nutrition, Métabolismes et Cancer [NuMeCan]
Pelletier, Romain [Auteur]
Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou]
Richeval, Camille [Auteur]
Impact de l'environnement chimique sur la santé humaine - ULR 4483 [IMPECS]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Gish, Alexandr [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Hakim, Florian [Auteur]
Impact de l'environnement chimique sur la santé humaine - ULR 4483 [IMPECS]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Ferron, Pierre-Jean [Auteur]
Nutrition, Métabolismes et Cancer [NuMeCan]
Mesli, Vadim [Auteur]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Unité de Taphonomie médico-légale et Anatomie - ULR 7367 [UTML&A]
Allorge, Delphine [Auteur]
Impact de l'environnement chimique sur la santé humaine - ULR 4483 [IMPECS]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]
Morel, Isabelle [Auteur]
Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou]
Nutrition, Métabolismes et Cancer [NuMeCan]
Gaulier, Jean-Michel [Auteur]
Impact de l'environnement chimique sur la santé humaine - ULR 4483 [IMPECS]
Centre Hospitalier Régional Universitaire [CHU Lille] [CHRU Lille]

Journal title :

Drug Testing and Analysis

Pages :

144-153

Publisher :

John Wiley

Publication date :

2022-01

ISSN :

1942-7603

English keyword(s) :

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

HAL domain(s) :

Sciences du Vivant [q-bio]
Sciences du Vivant [q-bio]/Sciences pharmaceutiques

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 mu M) and with HepaRG cells for two time periods (8 and 24 h) at one concentration (20 mu M). 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

Peer reviewed article :

Oui

Audience :

Internationale

Popular science :

Non

Collections :

• Unité de Taphonomie Médico-Légale & d’Anatomie (UTMLA) - ULR 7367

Source :

Harvested from HAL