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

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 ß-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.

Survey on health students' knowledge and perception on body donation for scientific research, education, and training after specific Italian law no. 10/2020.

BACKGROUND: Practicing on the human body was considered extremely relevant for health professionals' education, but a drastic reduction was observed due to an increase in alternative virtual and multimedia means, and, in Italy, also due to a lack of regulation. Italian Law 10/2020 regulates body donation for research and training through an advanced directive for post-mortem body donation. METHODS: A cross-sectional study was carried out to investigate the law knowledge and body donation perception of health students of any degree courses enrolled at the University of Pavia, Italy, in 2021, through ad hoc web questionnaire. RESULTS: 485 students participated to this survey; median age was of 21 years (25th-75th percentiles, 20-23), 73.2% were females, and 62.5% were medical students. Among them 14.9% knew the Italian law 10/2020. Age was the only variable associated with students' knowledge of the law. Further, 8.3% reported the current availability of cadaveric practice, 85.6% of health students acknowledged usefulness of cadaveric practice, with a significant difference between medical and non-medical students (71.4% vs 28.6%, p < 0.001). Overall, 59.7% would donate their body, rising to 62.7% with reference to specific law regulation, with 30.5% and 28.7% undecided, respectively. 51.3% of participants answered not practicing religious faith, 82.9% with Catholic families, without significance on the knowledge of the law. CONCLUSIONS: Poor knowledge of the law compared with great interest and acknowledged cadaveric practice usefulness highlighted the need for better information, especially among health students, where critical discussion could be more valuable. Then, there arises the urgent need to fill the gaps within university studies and syllabuses, to relaunch the central role that cadaveric practice and research had in the education of health professionals. Consequences on basic and specific health students' skills, on health education quality in general, and further on health professionals' expertise must be carefully considered.