Targeted Metabolic Investigation of Ligandrol and Analytical Methods Validation for Its Main Long-term Metabolite

Chempluschem. 2024 May;89(5):e202300634. doi: 10.1002/cplu.202300634. Epub 2024 Jan 22.

Abstract

Prompted by the need for related analytical reference material in the frame of the fight against doping in sports, synthetic efforts towards the main long-term bishydroxylated metabolite (LGD-LTM1) of the nonsteroidal selective androgen receptor modulator (SARM) ligandrol have produced related derivatives that were exploited for a targeted metabolite analysis of urine samples obtained in the course of previous excretion studies of this SARM. Further clarifying ligandrol's metabolic profile, the availability of synthetic reference material permitted the structural elucidation of a previously reported pyrrolidinone-type metabolite and revealed its potential analytical utility as an additional long-term marker. Moreover, synthetic reference material enabled the comparison and validation of liquid chromatography coupled with mass spectrometry (LC-MS)-based and gas chromatography coupled with mass spectrometry (GC-MS)-based detection and identification methods focusing on the LGD-LTM1 marker.

Keywords: Analytical Methods; Metabolite synthesis; Nitrogen heterocycles; Oxidation; Selective Androgen Receptor Modulators.

MeSH terms

  • Chromatography, Liquid / methods
  • Doping in Sports / prevention & control
  • Gas Chromatography-Mass Spectrometry*
  • Humans
  • Pyrrolidinones / chemistry
  • Pyrrolidinones / metabolism