Fatal intoxication related to two new arylcyclohexylamine derivatives (2F-DCK and 3-MeO-PCE)

Gicquel, Thomas; Richeval, Camille; Mesli, Vadim; Gish, Alexandr; Hakim, Florian; Pelletier, Romain; Cornez, Raphaël; Balgairies, Axelle; Allorge, Delphine; Gaulier, Jean-Michel

doi:10.1016/j.forsciint.2021.110852

Cited by 29 publications

(21 citation statements)

References 33 publications

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“…Snorted doses of 2F-DCK are generally between 87.5 and 330 mg, whereas those for ketamine are between 60 and 250 mg [ 75 ]. There are only two case reports on 2F-DCK consumption: a fatal case of DCK and 2-oxo-PCE intoxication in Germany [ 113 ] and our report on a patient at Lille University Medical Center (Lille, France) [ 19 ] ( Table 2 ).…”

Section: Arylcyclohexylamines: Clinical Toxicity and Forensic Casesmentioning

confidence: 96%

“…2F- DCK and 3-MeO-PCE were detected in the urine and bile of an intoxicated patient, suggesting the presence of both urinary and biliary excretion. Similarly, 2-F-DCK metabolites (including phase II metabolites) were found in the urine and bile of an intoxicated patient who subsequently died [ 19 ].…”

Section: Pharmacology Of Ketamine and Its Synthetic Derivativesmentioning

confidence: 99%

“…However, the advent of the Internet (and especially the Dark Web in the 2010s) and better logistics led to a huge increase in the consumption of ketamine and its derivatives. Cases of intoxication were first described in Asia, and are becoming more frequent in Europe [ 17 , 18 , 19 , 20 ]. Herein, we describe the pharmacology and metabolism of ACH derivatives and review the case reports on intoxication.…”

Section: Introductionmentioning

confidence: 99%

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Arylcyclohexylamine Derivatives: Pharmacokinetic, Pharmacodynamic, Clinical and Forensic Aspects

Pelletier

Daré

Bouëdec

et al. 2022

IJMS

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Since the 2000s, an increasing number of new psychoactive substances (NPS) have appeared on the drug market. Arylcyclohexylamine (ACH) compounds such as ketamine, phencyclidine and eticyclidine derivatives are of particular concern, given their rapidly increasing use and the absence of detailed toxicity data. First used mainly for their pharmacological properties in anesthesia, their recreational use is increasing. ACH derivatives have an antagonistic activity against the N-methyl-D-aspartate receptor, which leads to dissociative effects (dissociation of body and mind). Synthetic ketamine derivatives produced in Asia are now arriving in Europe, where most are not listed as narcotics and are, thus, legal. These structural derivatives have pharmacokinetic and pharmacodynamic properties that are sometimes very different from ketamine. Here, we describe the pharmacology, epidemiology, chemistry and metabolism of ACH derivatives, and we review the case reports on intoxication.

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Section: Arylcyclohexylamines: Clinical Toxicity and Forensic Casesmentioning

confidence: 96%

Section: Pharmacology Of Ketamine and Its Synthetic Derivativesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Arylcyclohexylamine Derivatives: Pharmacokinetic, Pharmacodynamic, Clinical and Forensic Aspects

Pelletier

Daré

Bouëdec

et al. 2022

IJMS

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“…Seized drug and other materials found near the victim can be an important source of information, guiding the toxicological screening and contributing to NPS discovery. Some papers retrieved in this review did describe the analysis of these materials (e.g., Papsun et al, 2016 ; Yonemitsu et al, 2016 ; Botinelli et al, 2017 ; Al-Matrouk et al, 2019 ; Deville et al, 2019 ; Ivanov et al, 2019 ; Gicquel et al, 2021 ). The drug characterization is also important to alert toxicology laboratories about possible new drugs on the market.…”

Section: Non-biological Materials Analysismentioning

confidence: 99%

“…In another French case, powder and crystals contained 3-MeO-PCP (72.9%) and various catinones were found, and blood concentration of the deceased were 498 ng/ml (peripheral) and 743 ng/ml (cardiac) ( Ameline et al, 2019 ). Gicguel et al (2021) reported the detection of 3-MeO-PCE (90 ng/ml) in peripheral blood, in addition to 2- fluorodeschloroketamine (2F-DCK) (1780 ng/ml) and a tryptamine analog, 5-MeO-DMT (52 ng/ml).…”

Section: Fatal Cases Involving New Psychoactive Substance Intakementioning

confidence: 99%

Fatal cases involving new psychoactive substances and trends in analytical techniques

et al. 2022

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New psychoactive substances (NPS) are an emerging public health issue and deaths are commonly associated with polydrug abuse. Moreover, the number of new substances available is constantly increasing, causing intoxications in low doses, characteristics that impose to toxicology and forensic laboratories to keep routine methods up to date, with high detectability and constantly acquiring new analytical standards. Likewise, NPS metabolites and respective elimination pathways are usually unknown, making it difficult the detection and confirmation of the drug involved in the fatal case in an analytical routine. A literature search was performed on PubMed, Scopus and Web of Science databases for papers related to chromatographic analyses from fatal cases related to NPS use published from 2016 to 2021. A total of 96 papers were retrieved and reviewed in this study. Opioids, synthetic cathinones, phenethylamines/amphetamines and cannabinoids were the NPS classes most found in the fatal cases. In many cases, multiple compounds were detected in the biological samples, including prescription and other illegal drugs. Liquid chromatography-tandem mass spectrometry, an alternative to overcome the gas chromatography–mass spectrometry limitations for some compounds, was the analytical technique most used in the studies, and high resolution mass spectrometry was often applied to NPS metabolite investigation and structural characterization and identification of unknown compounds. Toxicological screening and quantitation methods need to be continuously updated to include new substances that are emerging on the drug market that can be fatal at very low doses.

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Metabolite elucidation of 2‐fluoro‐deschloroketamine (2F‐DCK) using molecular networking across three complementary in vitro and in vivo models

Gicquel

Pelletier

Richeval

et al. 2021

Drug Testing and Analysis

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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.

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Fatal intoxication related to two new arylcyclohexylamine derivatives (2F-DCK and 3-MeO-PCE)

Cited by 29 publications

References 33 publications

Arylcyclohexylamine Derivatives: Pharmacokinetic, Pharmacodynamic, Clinical and Forensic Aspects

Arylcyclohexylamine Derivatives: Pharmacokinetic, Pharmacodynamic, Clinical and Forensic Aspects

Fatal cases involving new psychoactive substances and trends in analytical techniques

Metabolite elucidation of 2‐fluoro‐deschloroketamine (2F‐DCK) using molecular networking across three complementary in vitro and in vivo models

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