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A combined toxicokinetic and metabolic approach to investigate deschloro-N-ethylketamine exposure in a multidrug user.

Romain Magny, Bruno Mégarbane, Lucie Chevillard, Emmanuel Roulland, Benoit Bardèche-Trystram, Véronique Dumestre-Toulet, Laurence Labat, Pascal Houzé

Journal of Pharmaceutical and Biomedical Analysis June 15, 2024 DOI: 10.1016/j.jpba.2024.116086 (opens in new tab)

Study at a glance

AI-extracted from the abstract
Characteristics Case report Peer reviewed
Sample size 1
Population A chronic GHB, 3-MMC, and methoxetamine consumer in a chemsex context
Duration 29.5-hour period of plasma sampling
Topics Ketamine
Keywords 2-deschloro-n-ethylketamine Arylcyclohexylamine Molecular networking Multidrug user Toxicokinetics Designer drugs Research chemicals Drug testing Drug screening Drug metabolism pharmacokinetics Biotransformation
Citations 7
Key findings A multidrug exposure including the new psychoactive substance O-PCE was confirmed, with 27 metabolites identified and an elimination half-life of about 5 hours.

Abstract

The use of new psychoactive substances derived from ketamine is rarely reported in France. A chronic GHB, 3-MMC, and methoxetamine consumer presented a loss of consciousness in a chemsex context and was referred to the intensive care unit with a rapid and favorable outcome. To investigate the chemicals responsible for the intoxication, a comprehensive analysis was conducted on the ten plasma samples collected over a 29.5-hour period, urine obtained upon admission, a 2-cm hair strand sample, and a seized crystal. These analyses were performed using liquid chromatography hyphenated to high resolution tandem mass spectrometry operating in targeted and untargeted modes. Additionally, analyses using gas chromatography coupled to mass spectrometry and nuclear magnetic resonance were conducted to probe the composition of the seized crystal. The molecular network-based approach was employed for data processing in non-targeted analyses. It allowed to confirm a multidrug exposure encompassing GHB, methyl-(aminopropyl)benzofuran (MAPB), (aminopropyl)benzofuran (APB), methylmethcathinone, chloromethcathinone, and a new psychoactive substance belonging to the arylcyclohexylamine family namely deschloro-N-ethyl-ketamine (O-PCE). Molecular network analysis facilitated the annotation of 27 O-PCE metabolites, including phase II compounds not previously reported. Plasma kinetics of O-PCE allowed the estimation of the elimination half-life of ∼5 hours. Kinetics of O-PCE metabolites was additionally characterized, possibly useful as surrogate biomarkers of consumption. We also observed marked alterations in lipid metabolism related to poly consumption of drugs. In conclusion, this case report provides a comprehensive analysis of exposure to O-PCE in a multidrug user including kinetic and metabolism data in human.

Comparable studies

Other case reports and case series on ketamine, most cited first.

Study Year Design Participants
The destruction of the lower urinary tract by ketamine abuse: a new syndrome? Young recreational abusers of street-ketamine in Hong Kong referred to urology units 2008 Retrospective case series n = 59
Electroconvulsive Therapy, Ketamine, and Esketamine in a Patient with Major Depressive Disorder and Multiple Comorbidities: A Case Report over 10-year Treatment from Adolescence to Adulthood. A patient with treatment-resistant depression and comorbid generalized anxiety... 2025 Case report n = 1
Treatment of compulsive behaviour in eating disorders with intermittent ketamine infusions Chronic and treatment-resistant eating disorder patients 1998 Case series n = 15
Oral Administration of the NMDA Receptor Antagonist S-Ketamine as Add-On Therapy of Depression: A Case Series Four depressed patients taking standard antidepressants 2009 Case series n = 4
A longitudinal case series of IM ketamine for patients with severe and enduring eating disorders and comorbid treatment‐resistant depression Patients with enduring eating disorders and treatment-resistant depression 2021 Case series n = 4

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