Variation of Sequential Ligandrol (LGD-4033) Metabolite Levels in Routine Anti-Doping Urine Samples Detected with or without Other Xenobiotics

Abstract

Ligandrol, also known as LGD-4033, belongs to the group of selective androgen receptor modulators (SARMs). Ligandrol was first included in the WADA Prohibited List in 2018. This work presents a method that allows for the detection and identification of ligandrol and its metabolite in athletes’ urine and in dietary supplements by means of ultra performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS). Samples were prepared according to an approach involving acid hydrolysis and double liquid–liquid extraction (LLE). Furthermore, due to the lack of reference material for ligandrol metabolites, the urine collected from the control excretion study was analyzed. The presented method is appropriate to monitor ligandrol and its metabolites. The samples collected for doping control purpose contained multiple metabolites, which may potentially rule out the hypothesis of ingesting a single 1 µg or 10 µg dose only. Another aspect to take into account is that ligandrol can be applied together with SARMs, steroids, and GHSs. This will also affect the substances’ metabolism and elimination. It is also worth noting that dietary supplements may contain ligandrol as an official ingredient or as a contaminant. The described method may be usefully applied by other anti-doping or toxicological laboratories.