Prevalence and toxicological significance of 3-CMC and 4-CMC: A Retrospective study of over 250 forensic cases (2015-2025).

Synthetic cathinones remain a highly dynamic class of New Psychoactive Substances (NPS) across the global drug market. In Europe, chlorinated derivatives such as 3-chloromethcathinone (3-CMC) and 4-chloromethcathinone (4-CMC) have gained substantial popularity, posing significant public health and traffic safety risks. This study analyzes the occurrence and blood concentrations of 3-CMC and 4-CMC in Polish forensic cases over an 11-year period (2015-2025). Analytes were extracted from biological material via liquid-liquid extraction and quantified using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The study identified 81 cases of 3-CMC and 199 cases of 4-CMC, with 15 cases involving both substances, predominantly related to driving under the influence of drugs (DUID), traffic accidents, and fatalities. Although polydrug use was common, mono-intoxication occurred in 26 (3-CMC) and 56 (4-CMC) cases. Blood concentrations ranged from < 1 to 2680 ng/mL (mean: 68 ng/mL) for 3-CMC, and from < 1 to 2084 ng/mL (mean: 51 ng/mL) for 4-CMC. Fatal intoxications showed the highest mean concentrations (668 ng/mL for 3-CMC; 198 ng/mL for 4-CMC). To evaluate psychomotor impact, mono-substance DUID cases were analyzed, revealing mean concentrations of 15 ng/mL (3-CMC) and 42 ng/mL (4-CMC). Notably, traffic accidents involving only 4-CMC exhibited a mean concentration of 165 ng/mL. The findings document a significant shift in the illicit drug market, with chloromethcathinones replacing traditional stimulants like amphetamine. The established concentration profiles provide a vital epidemiological baseline and crucial reference data to aid forensic toxicologists and law enforcement in evaluating public health risks and drug-impaired driving.