In Vitro Metabolism of Metonitazene in Camels: High-Resolution Mass Spectrometric Characterization for Doping Control

Abstract

RATIONALE: Novel psychoactive substances, especially those within the benzimidazole class such as metonitazene, are powerful psychoactive agents with considerable potential for misuse in both human and animal sports. Implementing a robust detection and monitoring system is crucial to ensure fair competition and welfare of the athletes involved. METHODS: In vitro studies were conducted using camel liver homogenates to investigate the metabolism of metonitazene in camels. The metabolites were analyzed using a Thermo Fisher Orbitrap Exploris LC-MS system. Method validation for qualitative determination was performed using in-house developed methods, while data analysis and metabolite identification were performed using the Compound Discoverer software. RESULTS: A total of seven Phase I metabolites of metonitazene were successfully identified. The metabolic transformations were predominantly characterized by dealkylation reactions. These metabolites hold promise as potential markers for the long-term detection of metonitazene in camels for doping control applications. CONCLUSION: This study highlights the effectiveness of advanced high-resolution LC-MS techniques in identifying and characterizing the in vitro metabolites of metonitazene in camels. Considering the high potency and potential for abuse of metonitazene in camel racing, the metabolites identified offer a valuable basis for establishing robust doping control strategies. These results support the development of regulatory frameworks designed to protect animal welfare and uphold the integrity of the sport.