Investigation of the in vitro metabolism of the emerging drug candidate S107 for doping-preventive purposes

Journal of Mass Spectrometry

Volumn 46, Issue 2, 2011, Pages 112-130

  Beuck, S ^a   Thevis, M ^a   Schanzer W ^a  

^a GERMAN SPORT UNIVERSITY COLOGNE   (Germany)

Author keywords

doping; in vitro; mass spectrometry; metabolism; N glucuronide; rycal; S107; sport

Indexed keywords

DOPING; GLUCURONIDES; IN VITRO; RYCAL; S107; SPORT;

BIOMOLECULES; DENSITY FUNCTIONAL THEORY; DOPING (ADDITIVES); ELECTROSPRAY IONIZATION; ENZYMATIC HYDROLYSIS; ESCHERICHIA COLI; GLUCOSE; IODINE; ISOMERS; ISOTOPES; LIQUID CHROMATOGRAPHY; MASS SPECTROMETRY; METABOLITES; ORGANIC POLYMERS; PHYSIOLOGY; SYNTHESIS (CHEMICAL);

METABOLISM;

BENZOTHIAZEPINE DERIVATIVE; GLUCURONIC ACID; GLUCURONIDE; S107; UNCLASSIFIED DRUG;

ARTICLE; DEMETHYLATION; DOPING; ELECTROSPRAY MASS SPECTROMETRY; FRAGMENTATION REACTION; GLUCURONIDATION; HYDROLYSIS; IN VITRO STUDY; ISOTOPE LABELING; LIQUID CHROMATOGRAPHY; MASS SPECTROMETRY; OXIDATION; PRIORITY JOURNAL; SULFONATION; SYNTHESIS;

CHROMATOGRAPHY, LIQUID; DOPING IN SPORTS; FEMALE; HUMANS; MALE; SPECTROMETRY, MASS, ELECTROSPRAY IONIZATION; TANDEM MASS SPECTROMETRY; THIAZEPINES;

ESCHERICHIA COLI;

EID: 79951678237     PISSN: 10765174     EISSN: 10969888     Source Type: Journal    
DOI: 10.1002/jms.1878     Document Type: Article

References (20)

1. A. M. Bellinger, S. Reiken, M. Dura, P. W. Murphy, S. X. Deng, D. W. Landry, D. Nieman, S. E. Lehnart, M. Samaru, A. LaCampagne, A. R. Marks,. Remodeling of ryanodine receptor complex causes 'leaky' channels: a molecular mechanism for decreased exercise capacity. Proc. Natl. Acad. Sci. USA 2008, 105, 2198.
2. A. M. Bellinger, S. Reiken, C. Carlson, M. Mongillo, X. Liu, L. Rothman, S. Matecki, A. Lacampagne, A. R. Marks,. Hypernitrosylated ryanodine receptor calcium release channels are leaky in dystrophic muscle. Nat. Med. 2009, 15, 325.
3. M. Thevis, A. Thomas, M. Kohler, S. Beuck, I. Möller, M. Schäfer, G. Rodchenkov, S. Yin, J. A. Loo, H. Geyer, W. Schänzer,. Mass spectrometry-based characterization of new drugs and methods of performance manipulation in doping control analysis. Eur. J. Mass Spectrom. (Chichester, Engl) 2009, 16, 301.
4. M. Thevis, S. Beuck, A. Thomas, M. Kohler, N. Schlörer, I. Vajiala, W. Schänzer,. Screening for the calstabin-ryanodine receptor complex stabilisers JTV-519 and S-107 in doping control analysis. Drug Test. Anal. 2008, 1, 32.
5. M. Thevis, S. Beuck, A. Thomas, G. Fusshöller, G. Sigmund, N. Schlörer, G. Rodchenkov, M. Schäfer, W. Schänzer,. Electron ionization mass spectrometry of the ryanodine receptor-based Ca(2 +)-channel stabilizer S-107 and its implementation into routine doping control. Rapid Commun. Mass Spectrom. 2009, 23, 2363.
6. M. Thevis, S. Beuck, A. Thomas, B. Kortner, M. Kohler, G. Rodchenkov, W. Schänzer,. Doping control analysis of emerging drugs in human plasma-identification of GW501516, S-107, JTV-519, and S-40503. Rapid Commun. Mass Spectrom. 2009, 23, 1139.
7. T. Kuuranne, A. Leinonen, W. Schänzer, M. Kamber, R. Kostiainen, M. Thevis,. Aryl-propionamide-derived selective androgen receptor modulators: liquid chromatography-tandem mass spectrometry characterization of the in vitro synthesized metabolites for doping control purposes. Drug Metab. Dispos. 2008, 36, 571.
8. M. B. Fisher, K. Campanale, B. L. Ackermann, M. VandenBranden, S. A. Wrighton,. In vitro glucuronidation using human liver microsomes and the pore-forming peptide alamethicin. Drug Metab. Dispos. 2000, 28, 560.
9. R. Ramanathan, A. D. Su, N. Alvarez, N. Blumenkrantz, S. K. Chowdhury, K. Alton, J. Patrick,. Liquid chromatography/mass spectrometry methods for distinguishing N-oxides from hydroxylated compounds. Anal. Chem. 2000, 72, 1352.
10. P. Kulanthaivel, R. J. Barbuch, R. S. Davidson, P. Yi, G. A. Rener, E. L. Mattiuz, C. E. Hadden, L. A. Goodwin, W. J. Ehlhardt,. Selective reduction of N-oxides to amines: application to drug metabolism. Drug Metab. Dispos. 2004, 32, 966.
11. J. P. Perdew, K. Burke, M. Ernzerhof,. Generalized gradient approximation made simple. Phys. Rev. Lett. 1996, 77, 3865.
12. F. Weigend, M. Häser, H. Patzelt, R. Ahlrichs,. RI-MP2: optimized auxiliary basis sets and demonstration of efficiency. Chem. Phys. Lett. 1998, 294, 143.
13. F. Neese, ORCA-an ab initio, DFT and semiempirical SCF-MO package, Universität Bonn, 2008.
14. B. K. Matuszewski, M. L. Constanzer, C. M. Chavez-Eng,. Strategies for the assessment of matrix effect in quantitative bioanalytical methods based on HPLC-MS/MS. Anal. Chem. 2003, 75, 3019.
15. M. Holcapek, L. Kolarova, M. Nobilis,. High-performance liquid chromatography-tandem mass spectrometry in the identification and determination of phase I and phase II drug metabolites. Anal. Bioanal. Chem. 2008, 391, 59.
16. +-glucuronidation, a common pathway in human metabolism of drugs with a tertiary amine group. Drug Metab. Dispos. 1998, 26, 830.
17. M. D. Green, W. P. Bishop, T. R. Tephly,. Expressed human UGT1.4 protein catalyzes the formation of quaternary ammonium-linked glucuronides. Drug Metab. Dispos. 1995, 23, 299.
18. U. Mey, H. Wachsmuth, U. Breyer-Pfaff,. Conjugation of the enantiomers of ketotifen to four isomeric quaternary ammonium glucuronides in humans in vivo and in liver microsomes. Drug Metab. Dispos. 1999, 27, 1281.
19. P. Baranczewski, A. Stanczak, A. Kautiainen, P. Sandin, P. O. Edlund,. Introduction to early in vitro identification of metabolites of new chemical entities in drug discovery and development. Pharmacol. Rep. 2006, 58, 341.
20. M. Thevis, W. Schänzer,. Examples of doping control analysis by liquid chromatography-tandem mass spectrometry: ephedrines, beta-receptor blocking agents, diuretics, sympathomimetics, and cross-linked hemoglobins. J. Chromatogr. Sci. 2005, 43, 22.