Fatal intoxication involving amphetamine, clonazafone, a benzodiazepine prodrug, and fluoro-etonitazene, a new synthetic opioid

Intoxication cases involving new psychoactive substances (NPS) are known to provide various challenges for forensic toxicological case interpretation, starting with the identification of previously unknown substances. Furthermore, the pharmacological characteristics of these substances, including potency and metabolic processes, remain largely unstudied. In this particular medico-legal case, a 20-year-old man consumed clonazafone and fluoro-etonitazene, which were examined in blood by targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS). Additionally, a urine screening was conducted using LC-high-resolution mass spectrometry (HRMS) to investigate the metabolism of these substances, particularly clonazafone. Clonazafone was (semi-)quantified in urine (39 ng/mL), muscle tissue (3.0 ng/g), and stomach content (76'000 ng/mL), but could not be detected in peripheral blood, heart blood, and vitreous humor (lower limit of quantification: 0.1 ng/mL). Additionally, clonazepam (1.5 ng/mL) and its metabolite 7-amino-clonazepam (140 ng/mL), as well as amphetamine (110 ng/mL) and the designer-opioid fluoro-etonitazene (3.3 ng/mL) were found in blood. Within the HR screening, desglycylclonazafone, the intermediate of clonazafone that can be further converted into clonazepam, was detected in the stomach content and urine. Screening in urine has also revealed several metabolites of clonazafone. The cause of death was assumed to be a mixed drug intoxication with fluoro-etonitazene, clonazepam, and amphetamine.