In vitro characterization of protonitazene metabolites, using human liver microsomes, and first application to two urines collected from death cases.

Autor: Ameline A; Institut de Médecine Légale, 11 rue Humann, 67085 Strasbourg, France. Electronic address: ameline.alice@gmail.com., Gheddar L; Institut de Médecine Légale, 11 rue Humann, 67085 Strasbourg, France., Pichini S; Istituto Superiore di Sanita, 299 viale Regina Elena, 00161 Roma, Italy., Stove C; Laboratory of Toxicology, Campus Heymans, Ottergemsesteenweg 460, 9000 Gent, Belgium., Aknouche F; Laboratoire SYNLAB Réunion, 19 ter rue Balbolia, 97460 Saint-Paul, France., Maruejouls C; Laboratoire SYNLAB Réunion, 19 ter rue Balbolia, 97460 Saint-Paul, France., Raul JS; Institut de Médecine Légale, 11 rue Humann, 67085 Strasbourg, France., Kintz P; Institut de Médecine Légale, 11 rue Humann, 67085 Strasbourg, France; X-Pertise Consulting, 42 rue Principale, 67026 Mittelhausbergen, France.
Jazyk: angličtina
Zdroj: Clinica chimica acta; international journal of clinical chemistry [Clin Chim Acta] 2024 Jul 15; Vol. 561, pp. 119764. Date of Electronic Publication: 2024 Jun 04.
DOI: 10.1016/j.cca.2024.119764
Abstrakt: Protonitazene, or N,N-diethyl-5-nitro-2-[(4-propoxyphenyl)methyl]-1H-benzimidazole-1-ethanamine, is a novel synthetic opioid, which belongs to the nitazene family. Over the last four years, nitazenes have re-emerged on the new psychoactive substances market and have been reported in several fatal intoxication cases. The metabolism of several nitazene analogues have already been studied, but to date, no data exists regarding protonitazene. The aim of the study was the detection of protonitazene and its metabolites in authentic human urine collected in two fatal intoxication cases, comparing the data after in vitro incubation with human liver microsomes, and subsequent analysis by ultra-performance liquid chromatography-tandem mass spectrometry and ultra-performance liquid chromatography-high-resolution mass spectrometry. Protonitazene metabolites, including N-desethyl-protonitazene, 5-amino-protonitazene and 4-hydroxy-nitazene, were characterized in vitro and were identified in the urine of both cases. The ratios between metabolites and parent protonitazene, higher than 1, were calculated to estimate the proportionality of metabolites. The results suggest that testing protonitazene metabolites should increase the window detection of exposure to protonitazene.
(Copyright © 2024 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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