Mass spectrometry-based characterization of new drugs and methods of performance manipulation in doping control analysis

Efficient and comprehensive sports drug testing necessitates frequent updating and proactive, preventive anti-doping research and the early implementation of new, emerging drugs into routine doping controls is an essential aspect. Several new drugs and drug candidates with potential for abuse, including so-called Rycals (ryanodine receptor calstabin complex stabilizers, for example, S-107), hypoxia-inducible factor (HIF) stabilizers and peroxisome-proliferator-activated receptor (PPAR) delta agonists (for example, GW1516), were studied using different mass spectrometry- and ion mobility-based approaches and their gas-phase dissociation behaviors were elucidated. The detailed knowledge of fragmentation routes allows a more rapid identification of metabolites and structurally related, presumably tailor-made, analogs potentially designed for doping purposes. The utility of product ion characterization is demonstrated, in particular, with GW1516, for which oxidation products were readily identified in urine samples by means of diagnostic fragment ions, as measured using high-resolution/high-accuracy mass spectrometry and higher energy collision-induced dissociation (HCD).