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

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 Stability of Synthetic Cathinones and the Study of Potential Intake Biomarkers in the Biological Material from a Case of 3-CMC Poisoning.

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.

Post-aggression suicide under the influence of new psychoactive substances AMB-FUBINACA and U-47700.

The objective of the present study was the development and validation of the method for determining AMB-FUBINACA and its metabolite - AMB-FUBINACA O-desmethyl acid - in blood samples, followed by verification of the method in toxicological judicial and forensic medicine practice employing the example of post-aggression suicide. Most likely in consequence of development of adverse effects resulting in psychotic symptoms, a male being under the influence of the synthetic cannabinoid AMB-FUBINACA and the new synthetic opioid U-47700, mortally wounded his female partner and subsequently committed suicide. Identification and determination of the afore-mentioned xenobiotics in blood samples collected from the male and female victims were performed employing high performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS). The analytes were isolated from blood samples using the solid phase extraction (SPE) method. The blood samples collected from the male and female demonstrated respectively 110 and 196 ng/mL of AMB-FUBINACA O-desmethyl acid metabolite, 1935 and 357 ng/mL of U-47700, 250 and 200 ng/mL of N-desmethyl-U-47700, as well as 410 and 200 ng/mL of N,N-didesmethyl-U-47700. The concentration values of new psychoactive substances (NPS's) in blood samples originating from the male and female were within the ranges encountered in cases of poisoning, including these resulting in death. Nevertheless, the evident signs of exsanguination proof that the woman was alive when she sustained lethal injuries. The presented cases illustrate the difficult to be anticipated effect exerted on the users by NPS's.

Forensic-psychiatric relationships in the context of forensic medical examination of new psychoactive substance-related deaths.

INTRODUCTION: The aim of this study was to find causal relationships between the use of new psychoactive substances (NPS), the so-called "legal highs", and the cause of death, taking into account information indicating the victim's mental disorders before death. MATERIAL AND METHODS: The research material includes the results of toxicological analyses of blood samples collected during autopsies of 40 deceased persons whose cause of death was associated with the ingestion of new psychoactive substances (NPS). The blood samples were subjected to solid phase extraction (SPE), and then analyzed by liquid chromatography coupled with electrospray ionization tandem mass spectrometry (LC-ESI-MS-MS) for quantification. Information on individual cases was taken from case files provided by the prosecutor's office for research purposes. RESULTS: As a result of the analyses, 24 types of NPS were detected, comprising synthetic cathinones - 15 cases, synthetic cannabinoids - 10 cases, synthetic opioids - 13 cases, other - 2 cases. In the study group there were 5 women (12.5%) and 35 men (87.5%). Suicide was demonstrated in 10 cases (25%), while the remaining 30 cases (75%) were accidental deaths, including those in which the actual motivation of drug use could not be determined. Drugs used to treat mental disorders were detected in 6 cases, while analgesics were demonstrated in 5 cases. CONCLUSIONS: In the majority of cases, including suicides and accidental deaths where the manner of death was unknown, NPS use and consequent death from various causes are associated with psychiatric disorders.

Aspects related to analysis and medico-legal assessment in the context of the presence of synthetic cannabinoids in biological material based on the example of AB-CHMINACA.

AIM OF THE STUDY: The aim of this study was to develop and validate a method for the determination of the synthetic cannabinoid AB-CHMINACA in blood, followed by its verification in forensic toxicological practice. MATERIAL AND METHODS: The case of a 41-year-old man admitted to hospital because of scheduled cardiac surgery was discussed. The man died after 12 hours of hospitalization. Based on collected evidence, AB-CHMINACA poisoning was suspected. The identification and determination of AB-CHMINACA in the man's blood was performed by high-performance liquid chromatography coupled with tandem mass spectrometry using electrospray ionization (HPLC-ESI-MS-MS), after prior solid phase extraction. RESULTS: The concentration of AB-CHMINACA determined in the man's blood sample was 0.5 ng/ml. CONCLUSIONS: In the interpretation of the case, it was concluded that AB-CHMINACA had no direct effect on the patient's death, the cause of which was ascertained as chronic heart failure secondary to aortic valve disease, decompensated by pneumonia. However, an indirect impact of side effects resulting from the use of synthetic cannabinoids cannot be ruled out. They might have exacerbated the man's disease process leading to sudden cardiac arrest caused by asystole.