Expanding sports drug testing assays: Mass spectrometric characterization of the selective androgen receptor modulator drug candidates RAD140 and ACP-105

Rapid Communications in Mass Spectrometry

Volumn 27, Issue 11, 2013, Pages 1173-1182

  Thevis, Mario ^a,b   Piper, Thomas ^a   Beuck, Simon ^a   Geyer, Hans ^a   Schänzer, Wilhelm ^a  

^a GERMAN SPORT UNIVERSITY COLOGNE   (Germany)

^b European Monitoring Center for Emerging Doping Agents   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

CONTROLLED DRUG DELIVERY; DRUG PRODUCTS; IONIZATION OF GASES; LIQUID CHROMATOGRAPHY; MASS SPECTROMETERS; MASS SPECTROMETRY; MODULATORS; SPORTS;

ANABOLIC AGENTS; ANDROGEN RECEPTORS; DOPING CONTROL; DRUG CANDIDATES; DRUG TESTING; ELECTRON IONIZATION; ESI-MS-MS; MUSCLE ANABOLISM; QUADRUPOLE/TIME OF FLIGHTS; WORLD ANTI-DOPING AGENCY;

GAS CHROMATOGRAPHY;

EID: 84877313679     PISSN: 09514198     EISSN: 10970231     Source Type: Journal    
DOI: 10.1002/rcm.6558     Document Type: Article

References (31)

1. J. T. Dalton, A. Mukherjee, Z. Zhu, L. Kirkovsky, D. D. Miller,. Discovery of nonsteroidal androgens. Biochem. Biophys. Res. Commun. 1998, 244, 1.
2. T. Thum, J. Springer,. Breakthrough in cachexia treatment through a novel selective androgen receptor modulator? J. Cachexia Sarcopenia Muscle 2011, 2, 121.
3. M. L. Mohler, C. E. Bohl, A. Jones, C. C. Coss, R. Narayanan, Y. He, D. J. Hwang, J. T. Dalton, D. D. Miller,. Nonsteroidal selective androgen receptor modulators (SARMs): dissociating the anabolic and androgenic activities of the androgen receptor for therapeutic benefit. J. Med. Chem. 2009, 52, 3597.
4. R. Narayanan, M. L. Mohler, C. E. Bohl, D. D. Miller, J. T. Dalton,. Selective androgen receptor modulators in preclinical and clinical development. Nucl. Recept. Signal. 2008, 6, e010.
5. W. Gao, J. T. Dalton,. Expanding the therapeutic use of androgens via selective androgen receptor modulators (SARMs). Drug Discov. Today 2007, 12, 241.
6. M. L. Mohler, C. E. Bohl, R. Narayanan, Y. He, D. J. Hwang, J. T. Dalton, D. D. Miller, in Nuclear Receptors as Drug Targets, (Eds:, L E. Ottow, H. Weinmann,), Wiley-VCH, Weinheim, 2008, p. 249.
7. C. Sun, J. A. Robl, T. C. Wang, Y. Huang, J. E. Kuhns, J. A. Lupisella, B. C. Beehler, R. Golla, P. G. Sleph, R. Seethala, A. Fura, S. R. Krystek Jr, Y. An, M. F. Malley, J. S. Sack, M. E. Salvati, G. J. Grover, J. Ostrowski, L. G. Hamann,. Discovery of potent, orally-active, and muscle-selective androgen receptor modulators based on an N-aryl-hydroxybicyclohydantoin scaffold. J. Med. Chem. 2006, 49, 7596.
8. F. Nique, S. Hebbe, C. Peixoto, D. Annoot, J. M. Lefrancois, E. Duval, L. Michoux, N. Triballeau, J. M. Lemoullec, P. Mollat, M. Thauvin, T. Prange, D. Minet, P. Clement-Lacroix, C. Robin-Jagerschmidt, D. Fleury, D. Guedin, P. Deprez,. Discovery of diarylhydantoins as new selective androgen receptor modulators. J. Med. Chem. 2012, 55, 8225.
9. F. Nique, S. Hebbe, N. Triballeau, C. Peixoto, J. M. Lefrancois, H. Jary, L. Alvey, M. Manioc, C. Housseman, H. Klaassen, K. Van Beeck, D. Guedin, F. Namour, D. Minet, E. Van der Aar, J. Feyen, S. Fletcher, R. Blanque, C. Robin-Jagerschmidt, P. Deprez,. Identification of a 4-(hydroxymethyl) diarylhydantoin as a selective androgen receptor modulator. J. Med. Chem. 2012, 55, 8236.
10. A. van Oeveren, M. Motamedi, N. S. Mani, K. B. Marschke, F. J. Lopez, W. T. Schrader, A. Negro-Vilar, L. Zhi,. Discovery of 6-N,N-bis(2,2,2- trifluoroethyl)amino-4-trifluoromethylquinolin-2(1H)-one as a novel selective androgen receptor modulator. J. Med. Chem. 2006, 49, 6143.
11. A. van Oeveren, M. Motamedi, E. Martinborough, S. Zhao, Y. Shen, S. West, W. Chang, A. Kallel, K. B. Marschke, F. J. Lopez, A. Negro-Vilar, L. Zhi,. Novel selective androgen receptor modulators: SAR studies on 6-bisalkylamino-2-quinolinones. Bioorg. Med. Chem. Lett. 2007, 17, 1527.
12. E. G. Vajda, F. J. Lopez, P. Rix, R. Hill, Y. Chen, K. J. Lee, Z. O'Brien, W. Y. Chang, M. D. Meglasson, Y. H. Lee,. Pharmacokinetics and pharmacodynamics of LGD-3303 [9-chloro-2-ethyl-1-methyl-3-(2,2,2-trifluoroethyl) -3H-pyrrolo-[3,2-f]quinolin-7(6H)-one], an orally available nonsteroidal- selective androgen receptor modulator. J. Pharmacol. Exp. Ther. 2009, 328, 663.
13. X. Zhang, G. F. Allan, P. Tannenbaum, T. Sbriscia, O. Linton, M. T. Lai, D. Haynes-Johnson, S. Bhattacharjee, S. G. Lundeen, Z. Sui,. Pharmacological characterization of an imidazolopyrazole as novel selective androgen receptor modulator. J. Steroid Biochem. Mol. Biol. 2013, 134, 51.
14. K. Hanada, K. Furuya, N. Yamamoto, H. Nejishima, K. Ichikawa, T. Nakamura, M. Miyakawa, S. Amano, Y. Sumita, N. Oguro,. Bone anabolic effects of S-40503, a novel nonsteroidal selective androgen receptor modulator (SARM), in rat models of osteoporosis. Biol. Pharm. Bull. 2003, 26, 1563.
15. K. Furuya, N. Yamamoto, Y. Ohyabu, A. Makino, T. Morikyu, H. Ishige, K. Kuzutani, Y. Endo,. The novel non-steroidal selective androgen receptor modulator S-101479 has additive effects with bisphosphonate, selective estrogen receptor modulator, and parathyroid hormone on the bones of osteoporotic female rats. Biol. Pharm. Bull. 2012, 35, 1096.
16. P. Yi, J. F. Rehmel, K. Cassidy, C. Hadden, K. Campanale, N. Patel, J. Johnson,. Disposition and metabolism of LY2452473, a selective androgen receptor modulator, in humans. Drug Metab. Dispos. 2012, 40, 2354.
17. N. Schlienger, B. W. Lund, J. Pawlas, F. Badalassi, F. Bertozzi, R. Lewinsky, A. Fejzic, M. B. Thygesen, A. Tabatabaei, S. R. Bradley, L. R. Gardell, F. Piu, R. Olsson,. Synthesis, structure-activity relationships, and characterization of novel nonsteroidal and selective androgen receptor modulators. J. Med. Chem. 2009, 52, 7186.
18. M. Thevis, H. Geyer, A. Thomas, W. Schänzer,. Trafficking of drug candidates relevant for sports drug testing: Detection of non-approved therapeutics categorized as anabolic and gene doping agents in products distributed via the Internet. Drug Test. Anal. 2011, 3, 331.
19. M. Thevis, H. Geyer, M. Kamber, W. Schänzer,. Detection of the arylpropionamide-derived selective androgen receptor modulator (SARM) S-4 (Andarine) in a black-market product. Drug Test. Anal. 2009, 1, 387.
20. E. Grata, L. Perrenoud, M. Saugy, N. Baume,. SARM-S4 and metabolites detection in sports drug testing: a case report. Forensic Sci. Int. 2011, 213, 104.
21. C. P. Miller, M. Shomali, C. R. Lyttle, L. S. L. O'Dea, H. Herendeen, K. Gallacher, D. Paquin, D. R. Compton, B. Sahoo, S. A. Kerrigan, M. S. Burge, M. Nickels, J. L. Green, J. A. Katzenellenbogen, A. Tchesnokov, G. Hattersley,. Design, synthesis, and preclinical characterization of the selective androgen receptor modulator (SARM) RAD140. Med. Chem. Lett. 2011, 2, 124.
22. H. Budzikiewicz, C. Djerassi, D. H. Williams, Structure elucidation of natural products by mass spectrometry, vol. I: Alkaloids, Holden-Day, Inc., San Francisco, 1964.
23. H. Budzikiewicz, C. Djerassi, D. H. Williams, Interpretation of Mass Spectra of Organic Compounds, Holden-Day, Inc., San Francisco, 1964.
24. J. Diekman, J. B. Thomson, C. Djerassi,. Mass spectrometry in structural and stereochemical problems.141. Electron impact induced fragmentations and rearrangements of trimethylsilyl ethers amines and sulfides. J. Org. Chem. 1967, 32, 3904.
25. J. Byun, M. L. Gross, M. George, D. M. Parees, A. Z. Kamzelski, D. F. Swijter, D. A. Willcox,. Investigation of group migration in the fragmentation of bis(trimethylsilyl) ethers of diols separated by rigid groups. J. Mass Spectrom. 1997, 32, 71.
26. G. Petersson,. A McLafferty-type rearrangement of a trimethylsilyl group in silylated hydroxy carbonyl compounds. Org. Mass Spectrom. 1972, 6, 577.
27. A. Kasal, M. Budesinsky, W. J. Griffiths, in Steroid Analysis, (Eds:, H. L. J. Makin, D. B. Gower,), Springer, Heidelberg-London-New York, 2010, p. 27.
28. D. H. Catlin, B. D. Ahrens, Y. Kucherova,. Detection of norbolethone, an anabolic steroid never marketed, in athletes' urine. Rapid Commun. Mass Spectrom. 2002, 16, 1273.
29. D. H. Catlin, M. H. Sekera, B. D. Ahrens, B. Starcevic, Y.-C. Chang, C. K. Hatton,. Tetrahydrogestrinone: discovery, synthesis, and detection in urine. Rapid Commun. Mass Spectrom. 2004, 18, 1245.
30. B. Starcevic, B. D. Ahrens, A. W. Butch,. Detection of the selective androgen receptor modulator S-4 (Andarine) in a doping control sample. Drug Test. Anal. 2013, 5, in press.
31. M. Thevis, W. Schänzer,. Mass spectrometry of selective androgen receptor modulators. J. Mass Spectrom. 2008, 43, 865.