Kamil Synowiec

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.

The objective of the present study was to identify the metabolites of synthetic cathinone (SC), 3-chloromethcathinone (3-CMC), and to select a potential intake biomarker for this compound. The basis of the experiment was the analysis of blood and urine samples from a case of fatal poisoning with this substance. We also evaluated the stability of 3-CMC and the selected potential biomarker, the dihydro-3-CMC metabolite, depending on the time elapsed since the autopsy as well as the storage conditions of the biological material. Studies have shown that 3-CMC shows low stability in the biological material. However, acidification of the biological material or storage at low temperatures has a great impact on maintaining its stability. It is crucial to monitor the presence of the dihydro-3-CMC metabolite in the biological material during analysis, which showed high stability under all of the given storage conditions. SCs might not be detected in the biological material and, if they are, the determined concentrations at the time of testing may not correspond to the actual concentrations at the time of the event or death. Consequently, the interpretation of the results obtained for 3-CMC and dihydro-3-CMC in terms of assessing their toxicity and possible cause of death is difficult. The area of research into the search for other intake biomarkers of unstable halogen derivatives of SCs remains open.

Synthetic cathinones (SC) continue to represent the second largest group of substances on the drug market among new psychoactive substances (NPS). They have gained their fame mainly due to their amphetamine-like effects. The European Monitoring Centre for Drugs and Drug Addiction currently monitors over 830 NPS among which 156 are synthetic cathinone derivatives. The constant introduction of new derivatives often makes their identification in the examined evidence much more difficult. This is most often caused by the presence of isomers within the same group of substances as well as SC with similar chemical structures. Gas chromatography coupled to electron ionization mass spectrometry (GC-EI-MS) is the gold standard in their toxicological analysis. The aim of this study was to analyze 49 certified NPS standards from the SC group in the parent form and/or acetyl or trimethylsilyl derivatives by GC-EI-MS and to characterize their electron mass spectra. Additionally, an integrated application with the MassHunter software was used to create an authors’ library of SC including such parameters as retention times and mass spectra. The developed method allowed to achieve chromatographic separation of derivatives within a given group of positional isomers and SC with similar chemical structures. In the case of chloromethcathinone isomers, trimethylsilylation was necessary to achieve complete separation of these derivatives. The analysis of mass spectra of acetyl derivatives of SC allowed for their classification depending on the presence of characteristic m/z values. The obtained data allowed for the development of an automated library of mass spectra of these compounds with application potential for the purposes of forensic toxicology.