Cluster of acute poisonings associated with an emerging ketamine analogue, 2-oxo-PCE

Tang, Magdalene Huen Yin; Chong, Yeow Kuan; Chan, C. Y.; Ching, Chor Kwan; Lai, Chi-Kong; Li, YK; Mak, Tony Wing Lai

doi:10.1016/j.forsciint.2018.07.014

Cited by 30 publications

(21 citation statements)

References 21 publications

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“…The toxicity of O-PCE was reported to be more severe than ketamine as it seemed more potent at low dose. 6 Moreover, O-PCE can be used alone, or in mixture with ketamine or other drugs of abuse (methamphetamine, MDMA, pentylone), which could lead to more toxicity as reported by Cheng et al 5 In this study, O-PCE and its metabolite deschloro-norketamine were detected in blood in four driving under the influence (DUID) cases in the range of 80-310 and 40-90 ng/ml, respectively. 5 Knowledge about the metabolic pathways allows method development targeting the most relevant markers of drug intake, including parent drug and/or metabolites.…”

supporting

confidence: 54%

“…5 Although extensive pharmacological and toxicological data are available for ketamine, and to some extent for MXE, only few overdose cases with analytically confirmed acute O-PCE toxicity have been reported recently. 6,7 The main clinical symptoms associated with O-PCE use included impaired consciousness (84%), confusion (60%), abnormal behaviour (44%), hypertension (80%), tachycardia (40%) and convulsions (16%). The toxicity of O-PCE was reported to be more severe than ketamine as it seemed more potent at low dose.…”

mentioning

confidence: 99%

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Metabolic profiling of deschloro‐N‐ethyl‐ketamine and identification of new target metabolites in urine and hair using human liver microsomes and high‐resolution accurate mass spectrometry

Larabi

Zerizer

Ameline³

et al. 2021

Drug Testing and Analysis

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The aim of this study was to identify new markers of deschloro-N-ethyl-ketamine (O-PCE), a ketamine analogue that has been involved in acute intoxications with severe outcomes including death and whose metabolism has never been studied before. In vitro study after 2-h incubation with pooled human liver microsomes (HLMs) cross-checked by the analysis of urine and hair from a 43-year-old O-PCE user (male) were performed by liquid chromatography-high resolution mass spectrometry (LC-HRMS). Acquired data were processed by the Compound Discoverer® software, and a full metabolic profile of O-PCE was proposed. In total, 15 metabolites were identified, 10 were detected in vitro (HLMs) and confirmed in vivo (urine and/or hair), two were present only in HLMs, and the remaining three metabolites were identified only in biological specimens. While O-PCE was no longer detected in urine, nine metabolites were identified allowing to increase its detection window. In descending order of metabolites abundance, we suggest using 2-en-PCA-N-Glu (34%, first), M3 (16%, second), O-PCA-N-Glu (15.4%, third), OH-O-PCE (15%, fourth) and OH-PCE (11.9%, fifth) as target metabolites to increase the detection window of O-PCE in urine. In hair, nine metabolites were identified. OH-PCA was the major compound (78%) with a relevant metabolite to parent drug ratio (=6) showing its good integration into hair and making it the best marker for long-term monitoring of O-PCE exposure. K E Y W O R D S deschloro-N-ethyl-ketamine, hair, high-resolution mass spectrometry, human liver microsomes, new psychoactive substances 1 | INTRODUCTION Hallucinogens are a diverse group of naturally occurring or synthetic drugs that produce altered perception of reality known as 'Synaesthesia' observed with classic hallucinogens (e.g., LSD, dimethyltryptamine and 5-MeO-DMT), also referred to as 'psychedelics', or a feeling of detachment and dissociation from the self and the environment encountered with dissociative anaesthetics (e.g., ketamine, phencyclidine and methoxetamine). Classic hallucinogens act as serotonin receptor agonists while dissociative anaesthetics possess both stimulant and dissociative properties by inhibiting the reuptake of dopamine, norepinephrine and serotonin, and modulating effects at

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supporting

confidence: 54%

mentioning

confidence: 99%

Metabolic profiling of deschloro‐N‐ethyl‐ketamine and identification of new target metabolites in urine and hair using human liver microsomes and high‐resolution accurate mass spectrometry

Larabi

Zerizer

Ameline³

et al. 2021

Drug Testing and Analysis

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“…The 64 encounters related to 2-oxo-PCE, a ketamine analogue, occurred as a poisoning outbreak in late 2017. 12 Figure 1(a) shows the number of NPS of different subclasses encountered each year between 2009 and 2017 ( Figure 1(b) shows the same data excluding the 64 cases related to 2-oxo-PCE to avoid skewing of data).…”

Section: Resultsmentioning

confidence: 99%

“…One of the striking findings of this study was the surge in NPS use in 2017, which was mostly accounted for by the outbreak of 2-oxo-PCE, also known as deschloro-N-ethyl-ketamine late that year. 4,12 Putting aside these cases of 2-oxo-PCE, a steady rise in the overall number and variety of NPS detected is still appreciable over the years, which is alarming given the likely underestimation of NPS use (discussed below).…”

Section: Discussionmentioning

confidence: 99%

9-year review of new psychoactive substance use in Hong Kong: A clinical laboratory perspective

Tang

Hung

Lai

et al. 2018

Hong Kong Journal of Emergency Medicine

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Background: New psychoactive substances are constantly evolving structural analogues of traditional drugs of abuse that have become a threat to public health worldwide and within our locality. An understanding of the local pattern of new psychoactive substance use will help guide frontline clinical management. Objectives: This study was conducted to review the new psychoactive substances detected in cases referred to the authors' laboratory (a tertiary clinical toxicology centre), as well as the associated clinical features and toxicological findings. Methods: All cases referred to the laboratory for toxicology analysis between January 2009 and December 2017, and which were analytically confirmed to involve new psychoactive substance use, were retrospectively reviewed. Demographic data, clinical features and toxicology findings were studied. Results: A total of 111 cases involving 104 patients and 22 types of new psychoactive substances were identified, with an increasing trend in the number of cases and subclass of new psychoactive substances detected. Up to half of the cases (n = 64) were related to the use of 2-phenyl-2-(ethylamino)-cyclohexanone (2-oxo-PCE, a ketamine analogue); other new psychoactive substances detected included para-methoxymethamphetamine, 4-fluoroamphetamine, phenazepam, 3-trifluoromethylphenylpiperazine, 5-methoxy-diisopropyltryptamine, 2-diphenylmethylpyrrolidine, methoxyphenidine, the N-methoxybenzyl drugs, cathinones, synthetic cannabinoids and opioids. Among the acute poisoning cases attributable to new psychoactive substance use, the severity was fatal (n = 3), severe (n = 17), moderate (n = 67) and minor (n = 17). And 11 patients required intensive care unit admission. All three fatal cases were associated with paramethoxymethamphetamine use. Conclusion: A rising trend of new psychoactive substance use is observed locally, which is associated with considerable morbidity and mortality. Continued vigilance from frontline clinicians and medical professionals is imperative in the combat against new psychoactive substance use.

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“…We have previously reported an outbreak affecting 52 patients involving a ketamine analogue, 2-oxo-PCE, which is much more potent than ketamine and caused more severe clinical adverse effects. 1,2 We report the recent identification of two other ketamine analogues, 2-fluoro-deschloroketamine [2-(2-fluorophenyl)-2-methylamino-cyclohexanone] and deschloroketamine (2-phenyl-2-methylamino-cyclohexanone), in urine samples of two unrelated ketamine abusers.…”

Section: Ketamine Analogues Multiplying In Hong Kongmentioning

confidence: 99%

Ketamine analogues multiplying in Hong Kong

Lai²,

Tang

et al. 2019

Hong Kong Med J

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Cluster of acute poisonings associated with an emerging ketamine analogue, 2-oxo-PCE

Cited by 30 publications

References 21 publications

Metabolic profiling of deschloro‐N‐ethyl‐ketamine and identification of new target metabolites in urine and hair using human liver microsomes and high‐resolution accurate mass spectrometry

Metabolic profiling of deschloro‐N‐ethyl‐ketamine and identification of new target metabolites in urine and hair using human liver microsomes and high‐resolution accurate mass spectrometry

9-year review of new psychoactive substance use in Hong Kong: A clinical laboratory perspective

Ketamine analogues multiplying in Hong Kong

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