Comprehensive metabolic investigation of dopamine reuptake inhibitor HDMP-28 in equine liver microsomes and Cunninghamella elegans for doping control.

Autor: Muhammed Ajeebsanu M; Equine Forensic Unit, Central Veterinary Research Laboratory, Dubai, United Arab Emirates., Subhahar MB; Equine Forensic Unit, Central Veterinary Research Laboratory, Dubai, United Arab Emirates., Karakka Kal AK; Equine Forensic Unit, Central Veterinary Research Laboratory, Dubai, United Arab Emirates., Philip M; Equine Forensic Unit, Central Veterinary Research Laboratory, Dubai, United Arab Emirates., Perwad Z; Equine Forensic Unit, Central Veterinary Research Laboratory, Dubai, United Arab Emirates., Karatt TK; Equine Forensic Unit, Central Veterinary Research Laboratory, Dubai, United Arab Emirates., Graiban FM; Equine Forensic Unit, Central Veterinary Research Laboratory, Dubai, United Arab Emirates., Joseph M; Department of Bacteriology, Diagnostic Section, Central Veterinary Research Laboratory, Dubai, United Arab Emirates., Jose SV; Department of Bacteriology, Diagnostic Section, Central Veterinary Research Laboratory, Dubai, United Arab Emirates.
Jazyk: angličtina
Zdroj: Drug testing and analysis [Drug Test Anal] 2024 Oct; Vol. 16 (10), pp. 1182-1194. Date of Electronic Publication: 2024 Jan 15.
DOI: 10.1002/dta.3642
Abstrakt: A dopamine reuptake inhibitor is a type of medication or substance that works by blocking the reuptake of dopamine in the brain. Dopamine reuptake inhibitors offer multiple effects, including increased alertness, improved mood, and therapeutic potential for conditions like depression, ADHD, and Parkinson's disease. HDMP-28, or methylnaphthidate, is a potent synthetic stimulant from the phenyltropane class. It surpasses methylphenidate in both dopamine reuptake inhibition and half-life. As a dopamine reuptake inhibitor, it boosts dopamine levels by hindering reuptake into nerve cells, resulting in heightened stimulation and increased energy. In order to comprehensively address both the tangible and potential repercussions of the unauthorized utilization of the aforementioned substance in sports, it is imperative to establish analytical methodologies for the identification of the parent drug and its primary metabolites. Additionally, a comprehensive analysis of the metabolic characteristics of HDMP-28 in both human and animal subjects has yet to be published. This study explores the metabolic conversion of HDMP-28 mediated by equine liver microsomes and Cunninghamella elegans. An extraction and detection method was developed, optimized, and validated for doping assessment in equine urine and plasma. Liquid chromatography-high-resolution mass spectrometry was employed to determine metabolite structures. The study identified 31 (22 phase I and 9 phase II) metabolites of HDMP-28, including hydroxylated, hydrogenated, and hydrolyzed analogs. Glucuronic acid-conjugated metabolites were also detected. This manuscript describes metabolites based on the in vitro studies, which might not be the same in vivo. These findings aid in the detection and understanding of the illicit use of HDMP-28 in equestrian sports.
(© 2024 John Wiley & Sons Ltd.)
Databáze: MEDLINE
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