Screening for quinolinone-derived selective androgen receptor modulators using GC-MS and LC-MS/MS

The development of new compounds potentially complementing or replacing anabolic steroids is of great interest for pharmaceutical companies. Since 1998, non-steroidal anabolic agents termed selective androgen receptor modulators (SARMs) have been successfully introduced and investigated, and few have advanced to clinical trials. One class of SARMs is based on a 2-quinolinone nucleus, and the lead drug candidate LGD-2226 has demonstrated great anabolic potential and tissue selectivity. In order to control a possible misuse of these agents, reference material and model compounds were synthesized, characterized using mass spectrometric techniques, and validated detection methods were established using gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Quinolinone-derived SARMs such as LGD-2226 are efficiently detected using GC-MS as well as LC-MS/MS approaches. Due to the inclusion of SARMs in the prohibited list as issued by WADA in 2008, such compounds (even though not yet commercially available) need consideration in screening procedures and can be implemented into existing assays based on either gas- or liquid-chromatographic methods. Detection limits of conventional instruments are sufficient to uncover the misuse of LGD-2226, although studies on the metabolic face will be required to demonstrate whether the active drug or its metabolite(s) will be the best targets for doping control purposes. Aus dem Text (geändert)