Fatal mono-intoxication with Novel Synthetic Opioid Protonitazepyne (N-pyrrolidino protonitazene)

Nitazene analogues are highly potent new synthetic opioids increasingly implicated in fatal intoxications worldwide. Protonitazepyne (N-pyrrolidino protonitazene) is a recently identified derivative for which toxicological and postmortem data remain extremely limited, particularly in mono-intoxication cases. We report the first fatal mono-intoxication with protonitazepyne in <country> involving a 22-year-old man. Scene investigation revealed a suicide note, drug paraphernalia consistent with intranasal administration, and powder labeled as protonitazepyne purchased online as a “research chemical.” Postmortem examination demonstrated cerebral and pulmonary edema, right-sided cardiac dilatation, and generalized organ congestion, consistent with severe central respiratory depression. Comprehensive toxicological screening excluded other psychoactive substances. Quantitative analysis using a newly developed and validated LC-QTOF/MS method identified protonitazepyne concentrations of 34.6 ng/mL in peripheral blood, 62.2 ng/mL in gastric contents, and 476.0 ng/mL in bile. The absence of the parent compound and metabolites in urine suggests predominant hepatobiliary excretion. This case also provides the first experimental confirmation of protonitazepyne acid as a metabolite. It confirms the lethal potential of protonitazepyne as a sole agent, expand knowledge of its postmortem concentration ranges, matrix distribution and metabolic pathways. These findings highlight forensic and public health challenges posed by unregulated nitazene analogues and the need for enhanced oversight.