A fatal case involving the highest ever reported 4‐<scp>CMC</scp> concentration

Tusiewicz, Kaja; Chłopaś-Konowałek, Agnieszka; Wachełko, Olga; Zawadzki, Marcin; Szpot, Paweł

doi:10.1111/1556-4029.15162

Cited by 5 publications

(2 citation statements)

References 18 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The work of Tusiewicz et al. ( 19 ) described the highest concentration of 4-CMC to the present moment. A 22-year-old man was taken to the emergency room (ER) from a party, where, according to a witness’ statement: “1.5 hours before he had ingested orally 20 grams of mephedrone”.…”

Section: Resultsmentioning

confidence: 60%

Interpretative problems due to the presence of chloromethcathinone isomers in the biological material from postmortem cases

Romańczuk,

Rojek,

Synowiec

et al. 2023

Journal of Analytical Toxicology

View full text Add to dashboard Cite

While many new psychoactive substances often disappear from the drug market rather quickly, some, such as synthetic cathinones (SCs), still remain due to their popularity among users. The current knowledge of SC concentrations in blood samples is based mainly on the published case reports of intoxications or fatalities caused by SC intake. The aim of the present study was to present and interpret the obtained toxicological analysis results of these cases, in which it was possible to determine or detect the presence of one of the isomers of chloromethcathinone (CMC) along with its intake biomarker—dihydro-CMC. These cases include 27 deaths reported at the Department of Forensic Medicine in Kraków in 2016–2022. CMC constitutes a major toxicological opinion challenge, in terms of toxicological evaluation of poisonings. As presented in this paper, a significant problem is its stability in the biological material and practices in the reporting of the obtained data. It is therefore important to monitor potential intake biomarkers that may show greater stability in the biological material than the parent drug. In the case of CMC isomers, the good biomarker of intake is the dihydro-CMC metabolite, which was detected in the blood sample in every case presented, even with the absence of the parent substance. Interpretation of the results obtained for CMC in terms of assessing their toxicity and possible cause of death is difficult. However, it should be taken into account that in cases of new psychoactive substance poisoning, an in-depth risk assessment is mandatory and the opinion of the unpredictability of the effects is taken as a principle.

show abstract

Section: Resultsmentioning

confidence: 60%

Interpretative problems due to the presence of chloromethcathinone isomers in the biological material from postmortem cases

Romańczuk,

Rojek,

Synowiec

et al. 2023

Journal of Analytical Toxicology

View full text Add to dashboard Cite

show abstract

“…The only reports available are related to incidents involving this substance, though often, it is not the only substance implicated [ 4 ]. The highest reported concentration of 4-CMC in the blood and vitreous humor were, respectively, 8542 and 9874 ng/mL [ 22 ].…”

Section: Discussionmentioning

confidence: 99%

Toxicity of the New Psychoactive Substance (NPS) Clephedrone (4-Chloromethcathinone, 4-CMC): Prediction of Toxicity Using In Silico Methods for Clinical and Forensic Purposes

Jurowski,

Niżnik

2024

IJMS

View full text Add to dashboard Cite

This study reports the first application of in silico methods to assess the toxicity of 4-chloromethcathinone (4-CMC), a novel psychoactive substance (NPS). Employing advanced toxicology in silico tools, it was possible to predict crucial aspects of the toxicological profile of 4-CMC, including acute toxicity (LD50), genotoxicity, cardiotoxicity, and its potential for endocrine disruption. The obtained results indicate significant acute toxicity with species-specific variability, moderate genotoxic potential suggesting the risk of DNA damage, and a notable cardiotoxicity risk associated with hERG channel inhibition. Endocrine disruption assessment revealed a low probability of 4-CMC interacting with estrogen receptor alpha (ER-α), suggesting minimal estrogenic activity. These insights, derived from in silico studies, are critical in advancing the understanding of 4-CMC properties in forensic and clinical toxicology. These initial toxicological findings provide a foundation for future research and aid in the formulation of risk assessment and management strategies in the context of the use and abuse of NPSs.

show abstract

3-CMC, 4-CMC, and 4-BMC Human Metabolic Profiling: New Major Pathways to Document Consumption of Methcathinone Analogues?

Berardinelli,

Taoussi,

Daziani

et al. 2024

AAPS J

View full text Add to dashboard Cite

Synthetic cathinones represent one of the largest and most abused new psychoactive substance classes, and have been involved in numerous intoxications and fatalities worldwide. Methcathinone analogues like 3-methylmethcathinone (3-MMC), 3-chloromethcathinone (3-CMC), and 4-CMC currently constitute most of synthetic cathinone seizures in Europe. Documenting their consumption in clinical/forensic casework is therefore essential to tackle this trend. Targeting metabolite markers is a go-to to document consumption in analytical toxicology, and metabolite profiling is crucial to support investigations. We sought to identify 3-CMC, 4-CMC, and 4-bromomethcathinone (4-BMC) human metabolites. The substances were incubated with human hepatocytes; incubates were screened by liquid chromatography-high-resolution tandem mass spectrometry and data were mined with Compound Discoverer (Themo Scientific). 3-CMC-positive blood, urine, and oral fluid and 4-CMC-positive urine and saliva from clinical/forensic casework were analyzed. Analyses were supported by metabolite predictions with GLORYx freeware. Twelve, ten, and ten metabolites were identified for 3-CMC, 4-CMC, and 4-BMC, respectively, with similar transformations occurring for the three cathinones. Major reactions included ketoreduction and N-demethylation. Surprisingly, predominant metabolites were produced by combination of N-demethylation and ω-carboxylation (main metabolite in 3-CMC-positive urine), and combination of β-ketoreduction, oxidative deamination, and O-glucuronidation (main metabolite in 4-CMC-positive urine). These latter metabolites were detected in negative-ionization mode only and their non-conjugated form was not detected after glucuronide hydrolysis; this metabolic pathway was never reported for any methcathinone analogue susceptible to undergo the same transformations. These results support the need for comprehensive screening strategies in metabolite identification studies, to avoid overlooking significant metabolites and major markers of consumption. Graphical Abstract

show abstract

A fatal case involving the highest ever reported 4‐CMC concentration

Cited by 5 publications

References 18 publications

Interpretative problems due to the presence of chloromethcathinone isomers in the biological material from postmortem cases

Interpretative problems due to the presence of chloromethcathinone isomers in the biological material from postmortem cases

Toxicity of the New Psychoactive Substance (NPS) Clephedrone (4-Chloromethcathinone, 4-CMC): Prediction of Toxicity Using In Silico Methods for Clinical and Forensic Purposes

3-CMC, 4-CMC, and 4-BMC Human Metabolic Profiling: New Major Pathways to Document Consumption of Methcathinone Analogues?

Contact Info

Product

Resources

About