Quantification of the carboxylated LGD-4033 long-term metabolite in human micro-dose excretion study urine samples

Code: 25T04MT

A major concern both for athletes and result management authorities is the possibility of nutritional supplement/dietary product contamination with minute amounts of anabolic agents leading to adverse-analytical findings (AAFs) in doping controls. The analytical sensitivity of anti-doping laboratories has been optimized to allow for utmost retrospectivity in sports drug testing, but the problem arising from such a performance is that also trace amounts introduced into an athlete’s organism by contaminated supplements or food are detected.

To support the process of fair and comprehensive case management, in-depth investigations into the elimination profiles and metabolite ratios of micro-dosed LGD-4033 were conducted in 2020/21. For that purpose, single- and multi-micro-dose excretion studies at 1, 10 and 50 μg LGD-4033 were conducted, and the collected samples analyzed by enzymatic hydrolysis, solid-phase extraction (SPE) and LC-HRMS/MS. A total of 15 phase I metabolites was detected and the ratios of LGD-4033 and the epimer M1 as well as the metabolites M5-a and M5-b were found to shift over time. The combined evaluation of the LGD-4033/metabolite concentrations and ratios can be utilized to estimate whether a minute amount of the drug was recently ingested or a larger, pharmacologically relevant amount of the doping agent was administered several days/weeks ago and thus evaluate the plausibility of potential contamination scenarios.

Within this follow-up research project, the available micro-dose administration study samples will be re-analyzed to quantify the main long-term metabolite of LGD-4033 (M5-a) by using meanwhile available certified reference material.