Protonitazene metabolite variability in post-mortem casework.

Abstract

Protonitazene is a highly potent synthetic opioid that has recently emerged in the illicit drug supply. Data on its metabolism and the detection of its metabolites in post-mortem specimens are limited. This study retrospectively analysed 14 post-mortem cases to investigate metabolite profiles in blood and urine using high-resolution mass spectrometry. Detected metabolites included 5-aminoprotonitazene, N-desethylprotonitazene, and 4-hydroxynitazene. Additionally, a novel metabolite, hydroxyprotonitazene, previously only observed in liver microsome models, was identified. Significant variability in the metabolites detected across cases was observed, likely influenced by differences in metabolism, post-mortem changes, sampling methods, and metabolite stability. This study underscores the challenges of detecting protonitazene exposure and highlights the necessity of targeting multiple metabolites, as no single marker reliably indicated protonitazene use. Further research is needed to confirm metabolite identities, evaluate their stability, and understand their role in protonitazene toxicity.