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

Anal Bioanal Chem. 2008 May;391(1):251-61. doi: 10.1007/s00216-008-1882-6. Epub 2008 Feb 13.

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: see text]

Publication types

  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Androgen Antagonists / chemical synthesis
  • Androgen Antagonists / chemistry
  • Androgen Antagonists / urine*
  • Androgens
  • Benzimidazoles / chemistry
  • Benzimidazoles / urine*
  • Bridged Bicyclo Compounds / chemistry
  • Bridged Bicyclo Compounds / urine*
  • Chromatography, Liquid / methods
  • Humans
  • Hydantoins / chemistry
  • Hydantoins / urine*
  • Mass Screening / methods
  • Molecular Structure
  • Receptors, Androgen*
  • Tandem Mass Spectrometry / methods

Substances

  • 5,6-dichlorobenzimidazole
  • Androgen Antagonists
  • Androgens
  • Benzimidazoles
  • Bridged Bicyclo Compounds
  • Hydantoins
  • Receptors, Androgen
  • benzimidazole