Analytical and Bioanalytical Chemistry

, Volume 391, Issue 1, pp 251–261 | Cite as

Determination of benzimidazole- and bicyclic hydantoin-derived selective androgen receptor antagonists and agonists in human urine using LC–MS/MS

  • Mario Thevis
  • Maxie Kohler
  • Andreas Thomas
  • Joachim Maurer
  • Nils Schlörer
  • Matthias Kamber
  • Wilhelm Schänzer
Original Paper

Abstract

Selective androgen receptor modulators (SARMs) represent a novel class of drugs with tissue-specific agonistic and antagonistic properties, which are prohibited in sports from January 2008 according to the World Anti-Doping Agency. Preventive approaches to restrict the use of SARMs include early implementation of target analytes into doping control screening assays. Five model SARMs were synthesized, four of which are analogs to prostate-specific androgen receptor antagonists with a 5,6-dichloro-benzimidazole nucleus. The fifth SARM is a muscle-tissue specific agonist with a bicyclic hydantoin structure (BMS-564929). Dissociation pathways after negative electrospray ionization were studied using an LTQ-Orbitrap mass analyzer, and diagnostic product ions and common fragmentation patterns were employed to establish a screening procedure that target the intact SARMs as well as putative metabolic products. Sample preparation based on solid-phase extraction and subsequent LC–MS/MS measurement allowed for detection limits of 1–20 ng/mL, intra- and interday precisions of between 2.4 and 13.2% and between 6.5 and 24.2%, respectively. Recoveries varied from 89 to 106%, and tests for ion suppression or enhancement effects were negative for all analytes.

Figure

Precursor ion scanning as a tool to screen for the common nucleus of benzimidazole-derived SARMs

Keywords

Doping Sport Mass spectrometry Precursor ion scan SARMs Fragmentation Liquid chromatography 

Notes

Acknowledgments

The study was carried out with the support of the Federal Office of Sports, Magglingen, Switzerland, and the Manfred Donike Institute for Doping Analysis, Cologne, Germany.

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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Mario Thevis
    • 1
  • Maxie Kohler
    • 1
  • Andreas Thomas
    • 1
  • Joachim Maurer
    • 1
  • Nils Schlörer
    • 2
  • Matthias Kamber
    • 3
  • Wilhelm Schänzer
    • 1
  1. 1.Center for Preventive Doping Research, Institute of BiochemistryGerman Sport University CologneCologneGermany
  2. 2.Institute of Organic ChemistryUniversity of CologneCologneGermany
  3. 3.Department of Doping PreventionFederal Office of SportsMagglingenSwitzerland

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