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).
Thevis
Mario
M
Center for Preventive Doping Research-Institute of Biochemistry, German Sport University Cologne, Am Sportpark Müngersdorf 6, Cologne, Germany. thevis@dshs-koeln.de
Thomas
Andreas
A
Kohler
Maxie
M
Beuck
Simon
S
Möller
Ines
I
Schäfer
Mathias
M
Rodchenkov
Grigory
G
Yin
Sheng
S
Loo
Joseph A
JA
Geyer
Hans
H
Schänzer
Wilhelm
W
D004300:Doping in Sports / Q000517:prevention & control*; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D019966:Substance-Related Disorders / Q000175:diagnosis*; D013841:Thiazepines / Q000032:analysis; D013844:Thiazoles / Q000032:analysis / Q000378:metabolism
C425931:GW 501516; C540746:S-107 compound; D013841:Thiazepines; D013844:Thiazoles