Screening for Two Selective Androgen Receptor Modulators Using Gas Chromatography-Mass Spectrometry in Doping Control Analysis

Selective androgen receptor modulators (SARMs) have become a major field of clinical research enabling the tissue-selective stimulation of androgen receptors. The treatment of debilitating diseases, osteoporosis and frailty are primary goals and promising results have been obtained from clinical trials. However, the potential for misuse of SARMs in sport is great and drug testing methods based on liquid chromatography were established for different classes including arylpropionamide-, 2-quinolinone- and bicyclic hydantoin-derived compounds. As gas chromatography and mass spectrometry (GC-MS) are still important analytical tools in sports drug testing, a method to determine 2-quinolinone- and bicyclic hydantoin-derived SARMs established. Spiked urine samples were subjected to routine doping control protocols including enzymatic hydrolysis, liquid–liquid extraction, concentration and derivatisation to trimethylsilylated analogues followed by GC-MS analysis. The method was validated for the items specificity, lower limit of detection (0.2–10 ng mL−1), recovery (83–85%), intraday and interday precision (9–15% and 13–18%, respectively), which demonstrates the suitability of conventional GC-MS systems to determine representatives of an emerging class of compounds in doping control specimens.

[1]  M. Thevis,et al.  Mass spectrometry of hydantoin-derived selective androgen receptor modulators. , 2008, Journal of mass spectrometry : JMS.

[2]  M. Thevis,et al.  Determination of benzimidazole- and bicyclic hydantoin-derived selective androgen receptor antagonists and agonists in human urine using LC–MS/MS , 2008, Analytical and bioanalytical chemistry.

[3]  M. Thevis,et al.  Screening for 2-quinolinone-derived selective androgen receptor agonists in doping control analysis. , 2007, Rapid communications in mass spectrometry : RCM.

[4]  L. Freedman,et al.  Selective androgen receptor modulators for frailty and osteoporosis. , 2007, Current opinion in investigational drugs.

[5]  M. Nielen,et al.  Preventive doping control analysis: liquid and gas chromatography time-of-flight mass spectrometry for detection of designer steroids. , 2007, Rapid communications in mass spectrometry : RCM.

[6]  M. Thevis,et al.  Emerging drugs--potential for misuse in sport and doping control detection strategies. , 2007, Mini reviews in medicinal chemistry.

[7]  M. Thevis,et al.  Doping-Control Analysis of the 5α-Reductase Inhibitor Finasteride: Determination of Its Influence on Urinary Steroid Profiles and Detection of Its Major Urinary Metabolite , 2007, Therapeutic drug monitoring.

[8]  Min Wu,et al.  Discovery of an androgen receptor modulator pharmacophore based on 2-quinolinones. , 2007, Bioorganic & medicinal chemistry letters.

[9]  Wenqing Gao,et al.  Expanding the therapeutic use of androgens via selective androgen receptor modulators (SARMs). , 2007, Drug discovery today.

[10]  J. Dalton,et al.  Ockham's razor and selective androgen receptor modulators (SARMs): are we overlooking the role of 5alpha-reductase? , 2007, Molecular interventions.

[11]  L. Hamann,et al.  Discovery of potent, orally-active, and muscle-selective androgen receptor modulators based on an N-aryl-hydroxybicyclohydantoin scaffold. , 2006, Journal of medicinal chemistry.

[12]  T. Brown,et al.  Selective androgen receptor modulators: in pursuit of tissue-selective androgens. , 2006, Current opinion in investigational drugs.

[13]  Arjan van Oeveren,et al.  Discovery of 6-N,N-bis(2,2,2-trifluoroethyl)amino- 4-trifluoromethylquinolin-2(1H)-one as a novel selective androgen receptor modulator. , 2006, Journal of medicinal chemistry.

[14]  J. Dalton,et al.  Pharmacokinetics and Pharmacodynamics of Nonsteroidal Androgen Receptor Ligands , 2006, Pharmaceutical Research.

[15]  M. Thevis,et al.  Screening for metabolically stable aryl-propionamide-derived selective androgen receptor modulators for doping control purposes. , 2006, Rapid communications in mass spectrometry : RCM.

[16]  Shalender Bhasin,et al.  Drug Insight: testosterone and selective androgen receptor modulators as anabolic therapies for chronic illness and aging , 2006, Nature Clinical Practice Endocrinology &Metabolism.

[17]  M. Nielen,et al.  Urine testing for designer steroids by liquid chromatography with androgen bioassay detection and electrospray quadrupole time-of-flight mass spectrometry identification. , 2006, Analytical chemistry.

[18]  Duane D. Miller,et al.  Nonsteroidal tissue selective androgen receptor modulators: a promising class of clinical candidates , 2005 .

[19]  M. Thevis,et al.  Screening for unknown synthetic steroids in human urine by liquid chromatography-tandem mass spectrometry. , 2005, Journal of mass spectrometry : JMS.

[20]  M. T. A. W. Schanzer Mass Spectrometry in Doping Control Analysis , 2005 .

[21]  C. Georgakopoulos,et al.  Another designer steroid: discovery, synthesis, and detection of 'madol' in urine. , 2005, Rapid communications in mass spectrometry : RCM.

[22]  Duane D. Miller,et al.  A Selective Androgen Receptor Modulator for Hormonal Male Contraception , 2005, Journal of Pharmacology and Experimental Therapeutics.

[23]  David Handelsman Designer Androgens in Sport: When Too Much Is Never Enough , 2004, Science's STKE.

[24]  Yu-Chen Chang,et al.  Tetrahydrogestrinone: discovery, synthesis, and detection in urine. , 2004, Rapid communications in mass spectrometry : RCM.

[25]  U. Hengge Testosterone replacement for hypogonadism: clinical findings and best practices. , 2003, The AIDS reader.

[26]  D. B. Gower,et al.  Anabolic steroids in sport: biochemical, clinical and analytical perspectives , 2003, Annals of clinical biochemistry.

[27]  D. Catlin,et al.  Detection of norbolethone, an anabolic steroid never marketed, in athletes' urine. , 2002, Rapid communications in mass spectrometry : RCM.

[28]  Duane D. Miller,et al.  Discovery of nonsteroidal androgens. , 1998, Biochemical and biophysical research communications.

[29]  K. Biemann,et al.  A mass spectrometric method for the determination of stable isotope labeled phenytoin suitable for pulse dosing studies. , 1980, Biomedical mass spectrometry.

[30]  R. T. Coutts,et al.  The mass spectra of succinimides, hydantoins, oxazolidinediones and other medicinal anti‐epileptic agents , 1970 .

[31]  M. Thevis,et al.  Current role of LC–MS(/MS) in doping control , 2007, Analytical and bioanalytical chemistry.

[32]  M. Thevis,et al.  Mass spectrometry in sports drug testing: Structure characterization and analytical assays. , 2007, Mass spectrometry reviews.

[33]  L. Gooren,et al.  Androgen replacement therapy: present and future. , 2004, Drugs.

[34]  E. Nieschlag,et al.  Progress towards hormonal male contraception. , 2004, Trends in pharmacological sciences.

[35]  Andrew J. Hutt,et al.  Recent Advances in Doping Analysis , 2002 .

[36]  G. O. Potts,et al.  Dissociation of the Androgenic and Other Hormonal Activities from the Protein Anabolic Effects of Steroids , 1976 .