Investigation of in vitro generated metabolites of LGD-4033, a selective androgen receptor modulator, in homogenized camel liver for anti-doping applications.

RATIONALE: The use of selective androgen receptor modulators (SARM) in sports is prohibited by the World Anti-Doping Agency (WADA) due to their potential as performance-enhancing drugs, offering an unfair advantage. LGD-4033 is a SARM known for its similarities to anabolic steroids and can be easily purchased online, leading to increased availability and misuse. Adverse analytical findings have revealed the presence of SARMs in dietary supplements. Although LGD-4033 misuse has been reported in human sports over the years, concerns also arise regarding its illicit use in animal sports, including camel racing. Although various studies have investigated the metabolism of LGD-4033 in humans, horse, and other species, there is limited research specifically dedicated to racing camels. METHODS: This study focuses on the in vitro metabolism of LGD-4033 in homogenized camel liver using liquid chromatography-high-resolution mass spectrometry (LC-HRMS) to identify and characterize the metabolites. RESULTS: The findings indicated the presence of 12 phase I metabolites and 1 phase II metabolite. Hydroxylation was responsible for the formation of the main phase I metabolites that were identified. A glucuronic acid conjugate of the parent drug was observed in this study, but no sulfonic acid conjugate was found. The possible chemical structures of these metabolites, along with their fragmentation patterns, were identified using MS. CONCLUSIONS: These findings provide valuable insights into the metabolism of LGD-4033 in camels and aid in the development of effective doping control methods for the detection of SARMs in camel racing.

Comprehensive metabolite profiling of trimetazidine in camels using high-resolution accurate mass spectrometry: Implications for doping control.

RATIONALE: Trimetazidine and its metabolites are prohibited substances in sports. With a growing number of adverse findings in human athletes, it is crucial to develop doping control strategies that include screening for trimetazidine in animal sports. This study aims to detect and characterize trimetazidine and its metabolites for doping control in camel racing. METHODS: Camel urine and plasma samples were collected from four healthy animals following a single oral dose of trimetazidine. In vitro investigations were conducted using camel liver samples. Liquid-liquid extraction and solid-phase extraction techniques were employed for the extraction of trimetazidine metabolites from plasma and urine matrices. The metabolites were analyzed using a Thermo Orbitrap Exploris LC-MS system with optimized settings to achieve maximum sensitivity and accurate mass measurements. RESULTS: Comprehensive metabolite profiling of trimetazidine in camels revealed the identification of seven phase I and five phase II metabolites. Phase I metabolites were primarily formed through dealkylation, while phase II metabolites were dominated by glucuronide conjugation of demethylated trimetazidine. The findings provided insights into the distinct metabolic pathways and biotransformation patterns of trimetazidine in camels under the experimental conditions. CONCLUSION: The developed method enables detection and characterization of trimetazidine and its metabolites in camels. The identified metabolites have the potential to serve as marker metabolites for trimetazidine abuse in camel racing. This study provides valuable insights into the metabolism of trimetazidine in camels.