First French case of fatal NPS poly-consumption involving bromazolam and 2-MMC: insights from NMR and LC-HRMS.

Identifying poorly documented molecules as new psychoactive substances (NPS) is essential in toxicologically induced death cases. We report here the case of a 42-year-old woman who died in a context of NPS poly-consumption. Near the body were 10 bags labeled as Research Chemicals. Three of them, identified as bromazolam and 2-MMC, were empty. The seven other bags, labeled 4 F-MPH, 4-FMA, 2-MMC and O-DSMT contained tablets of various shapes and colors. The tablets and post-mortem blood samples were collected and analyzed. 1H NMR analyses (500 MHz, Bruker spectrometer) were performed on the tablets extracts. NPS identification and quantification in blood were performed using liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS) (Q-Exactive®, Thermo Scientific). The post-mortem peripheral blood results showed the following concentrations: bromazolam 308 ng/mL, 2-MMC 12,616 ng/mL, O-desmethyl-tramadol 1,410 ng/mL, 4-FMA 3,176 ng/mL and 4 F-MPH 121 ng/mL. 2-MMC concentrations were higher compared to usual “lethal” concentrations reported in the literature. This study represents the first documented case of bromazolam use in France. 1H NMR analysis allowed to correlate the tablets content to the bag labelling, except for the sample 4 F-MPH which corresponds to 4-FMA. The identification and quantification of the NPS mixture in the blood allow us to conclude the toxicological origin of the cause of death. This case emphasizes the forensic relevance of establishing lethal doses for various NPS and highlights the analytical value of integrating NMR and LC-HRMS techniques for tablet identification to discriminate structural isomers and mislabeled NPS bags.