Mass spectrometry of hydantoin-derived selective androgen receptor modulators

N-Aryl-hydroxybicyclohydantoins represent a new class of tissue-selective anabolic agents [selective androgen receptor modulators (SARMs)] and are promising therapeutics as well as drugs prohibited in amateur and professional sport. The dissociation behavior after negative and positive electrospray ionization (ESI) and subsequent collision-induced dissociation (CID) was studied with a drug candidate (BMS 564929) as well as structurally related and isotope-labeled analogs using high resolution/high accuracy orbitrap mass spectrometry. Positive ionization and CID yielded characteristic product ions resulting from the cleavage of the hydantoin structure providing information about the proline-derived nucleus as well as the substituted aryl residue at m/z 96 and 193, respectively. Negative ESI and CID (MS/MS) yielded product ions mainly representing losses of water and CO(2), the latter of which is of particular significance as the hydantoin structure does not contain a carboxyl function. Employing MS(n) experiments with accurate mass determination on six model SARMs, dissociation pathways to characteristic product ions were proposed supporting the identification of these drugs, their metabolites or related compounds in future doping control assays.