Detection of LGD-4033 Metabolites in Camel Urine, Plasma, and Hair Following Oral Administration for Doping Control

Rationale

LGD-4033, a selective androgen receptor modulator (SARM), is recognized for promoting muscle growth and enhancing athletic performance. Its potent anabolic effects have led to its prohibition in both human and animal sports. Although initial in vitro studies have offered insights into its metabolism, an in-depth in vivo analysis is necessary to fully understand its metabolic pathways. This research aims to thoroughly investigate the metabolic profile of LGD-4033 in camels to establish reliable analytical markers, thereby addressing an important gap in the doping detection in camel racing.

Methods

Urine, plasma, and hair samples were collected from three healthy camels following a single oral administration of 100 mg LGD-4033 mixed with food. These biological samples were then analyzed using ultrahigh-performance liquid chromatography coupled with high-resolution Q Exactive Orbitrap mass spectrometry (UHPLC-HRMS).

Results

Fourteen metabolites were identified across all sample types. The main Phase I metabolite, M6 (dihydroxylation), appears to be a primary target analyte for urine-based doping analysis. Both dihydroxy and trihydroxy metabolites were notably abundant in urine, accompanied by glucuronic and sulfonic acid conjugates; however, sulfonic acid conjugates were absent in in-vitro studies. Further research on hair samples, especially at higher LGD-4033 dosages, is recommended.

Conclusions

The findings from this study will improve the rapid identification of LGD-4033 and related compounds, supporting effective doping control in camel racing. These results enhance understanding of LGD-4033 metabolism in camels and advance the development of reliable methods for detecting SARMs in this field.