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Mass spectrometry of hydantoin‐derived selective androgen receptor modulators
Author(s) -
Thevis Mario,
Kohler Maxie,
Schlörer Nils,
Kamber Matthias,
Kühn Andreas,
Linscheid Michael W.,
Schänzer Wilhelm
Publication year - 2008
Publication title -
journal of mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 121
eISSN - 1096-9888
pISSN - 1076-5174
DOI - 10.1002/jms.1364
Subject(s) - chemistry , orbitrap , electrospray ionization , mass spectrometry , hydantoin , dissociation (chemistry) , aryl , tandem mass spectrometry , chromatography , stereochemistry , biochemistry , organic chemistry , alkyl
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. Copyright © 2007 John Wiley & Sons, Ltd.