Characterization of desoxymethyltestosterone main urinary metabolite produced from cultures of human fresh hepatocytes

Steroids

Volumn 77, Issue 6, 2012, Pages 635-643

  Gauthier, Julie ^a   Poirier, Donald ^b   Ayotte, Christiane ^a  

^a INRS INSTITUT ARMAND FRAPPIER   (Canada)

^b LAVAL UNIVERSITY   (Canada)

Author keywords

Desoxymethyltestosterone; GC MS; Hepatocytes; Metabolites; Synthesis

Indexed keywords

17ALPHA METHYL 2BETA,3ALPHA,17BETA TRIHYDROXY 5ALPHA ANDROSTANE; 17BETA HYDROXY 17ALPHA METHYL 1ALPHA,2ALPHA SPIROOXIRANE 5ALPHA ANDROST 3 ONE; 17BETA HYDROXY 17ALPHA METHYL 5ALPHA ANDROST 1 EN 3 ONE; 17BETA HYDROXY 17ALPHA METHYL 5ALPHA ANDROSTAN 2 EN 4 ONE; 17BETA HYDROXY 17ALPHA METHYL 5ALPHA ANDROSTAN 3 ENE; 17BETA HYDROXY 5ALPHA ANDROST 2 ENE 4 ONE; 1ALPHA,17BETA DIHYDROXY 17ALPHA METHYL 5ALPHA ANDROST 2 ENE; 1BETA,17BETA DIHYDROXY 17ALPHA METHYL 5ALPHA ANDROST 2 ENE; 2ALPHA BROMO 17BETA HYDROXY 17ALPHA METHYL 5ALPHA ANDROSTAN 3 ONE; 3ALPHA BROMO 17BETA HYDROXY 17ALPHA METHYL 5ALPHA ANDROSTAN 4 ENE; 3BETA,17BETA DIHYDROXY 17ALPHA METHYL 5ALPHA ANDROST 2 ENE; 4EPSILON,17BETA DIHYDROXY 17ALPHA METHYL 5ALPHA ANDROST 2 ENE; 4EPSILON,17BETA DIHYDROXY 17ALPHA METHYL 5ALPHA ANDROSTAN 2 ENE; 4EPSILON,17BETA DIHYDROXY 5ALPHA ANDROST 2 ENE; DESOXYMETHYLTESTOSTERONE; MESTANOLONE; METHYLTESTOSTERONE; STEROID; UNCLASSIFIED DRUG;

ARTICLE; CELL CULTURE; DRUG ISOLATION; DRUG MANUFACTURE; DRUG SYNTHESIS; HUMAN; HUMAN CELL; HUMAN TISSUE; LIVER CELL; LIVER HOMOGENATE; MASS SPECTROMETRY; NUCLEAR MAGNETIC RESONANCE; URINALYSIS;

ANDROSTENOLS; CELLS, CULTURED; DOPING IN SPORTS; HEPATOCYTES; HUMANS; MASS SPECTROMETRY; REFERENCE STANDARDS;

EID: 84859843408     PISSN: 0039128X     EISSN: 18785867     Source Type: Journal    
DOI: 10.1016/j.steroids.2012.02.008     Document Type: Article

References (33)

1. Ayotte C, Goudreault D, Cyr D, Gauthier J, Ayotte P, Larochelle C, Poirier D. Characterisation of chemical and pharmacological properties of new steroids related to doping of athletes. In: Manfred Donike Workshop, 24th Cologne Workshop on Dope Analysis. Cologne; 2006.
2. WADA. WADA announces discovery of new designer steroid; 2005. Available from: 〈http://www.wada-ama.org/en/newsarticle.ch2?articleID=3115089〉.
3. HealthCanada, Health Canada advises consumers not to use unauthorized products containing anabolic steroids. Health Canada: Ottawa; 2006.
4. Hartgens F, Kuipers H. Effects of androgenic-anabolic steroids in athletes. Sports Med 2004;34(8):513-54. (Pubitemid 38981844)
5. Bahrke MS, Yesalis CE. Abuse of anabolic androgenic steroids and related substances in sport and exercise. Curr Opin Pharmacol 2004;4(6):614-20. (Pubitemid 40267877)
6. Kutscher EC, Lund BC, Perry PJ. Anabolic steroids: a review for the clinician. Sports Med 2002;32(5):285-96. (Pubitemid 34450633)
7. Diel P, Friedel A, Geyer H, Kamber M, Laudenbach-Leschowsky U, Schanzer W, Thevis M, Vollmer G, Zierau O. Characterisation of the pharmacological profile of desoxymethyltestosterone (Madol), a steroid misused for doping. Toxicol Lett 2007;169(1):64-71. (Pubitemid 46215956)
8. WADA. 2006. Available from: 〈http://www.wada-ama.org/rtecontent/ document/Explanatory-Note-2006.pdf〉.
9. Sekera MH, Ahrens BD, Chang YC, Starcevic B, Georgakopoulos C, Catlin DH. Another designer steroid: discovery, synthesis, and detection of 'madol' in urine. Rapid Commun Mass Spectrom 2005;19(6):781-4. (Pubitemid 40349418)
10. Rodchenkov G, Sobolevsky T, Sizoi V. New Designer Anabolic Steroids from Internet. In: Manfred Donike Workshop, 24th Cologne Workshop on Dope Analysis. Cologne; 2006.
11. Kuuranne T, Kurkela M, Thevis M, Schanzer W, Finel M, Kostiainen R. Glucuronidation of anabolic androgenic steroids by recombinant human UDP-glucuronosyltransferases. Drug Metab Dispos 2003;31(9):1117-24. (Pubitemid 37048283)
12. Kuuranne T, Leinonen A, Thevis M, Schanzer W, Pystynen KH, Kostiainen R. Metabolism of "new" anabolic steroids: development of in vitro methodology in metabolite production and analytical techniques. In: Manfred Donike Workshop 24th Cologne Workshop on Dope Analysis. Cologne; 2006.
13. Hintikka L, Kuuranne T, Aitio O, Thevis M, Schanzer W, Kostiainen R. Enzyme-assisted synthesis and structure characterization of glucuronide conjugates of eleven anabolic steroid metabolites. Steroids 2008;73(3):257-65.
14. Rendic S, Nolteernsting E, Schanzer W. Metabolism of anabolic steroids by recombinant human cytochrome P450 enzymes. Gas chromatographic-mass spectrometric determination of metabolites. J Chromatogr B 1999;735(1):73-83. (Pubitemid 30122716)
15. Levesque JF, Gaudreault M, Aubin Y, Chauret N. Discovery, biosynthesis, and structure elucidation of new metabolites of norandrostenedione using in vitro systems. Steroids 2005;70(4):305-17. (Pubitemid 40387385)
16. Levesque JF, Gaudreault M, Houle R, Chauret N. Evaluation of human hepatocyte incubation as a new tool for metabolism study of androstenedione and norandrostenedione in a doping control perspective. J Chromatogr B 2002;780(1):145-53. (Pubitemid 35279753)
17. Levesque JF, Templeton E, Trimble L, Berthelette C, Chauret N. Discovery, biosynthesis, and structure elucidation of metabolites of a doping agent and a direct analogue, tetrahydrogestrinone and gestrinone, using human hepatocytes. Anal Chem 2005;77(10):3164-72. (Pubitemid 40695472)
18. Gauthier J, Goudreault D, Poirier D, Ayotte C. Identification of drostanolone and 17-methyldrostanolone metabolites produced by cryopreserved human hepatocytes. Steroids 2009;74(3):306-14.
19. Poirier D, Maltais R, Roy J. 2-(N-substituted piperazinyl) steroid derivatives, WO 2010/060215 A1; 2010.
20. Celsis IVT. Fresh Hepatocyte Suspension. 2007. Available from: 〈http://www.celsis.com/media/pdf/filelib/ps-fresh-human-animal-hepatocyte- suspensions.pdf〉.
21. Celsis-In Vitro, T. Products > Cryopreserved Hepatocytes. Available from: 〈http://www.invitrotech.com/cryo-hepatocytes.cfm〉.
22. Ayotte C, Goudreault D, Charlebois A. Testing for natural and synthetic anabolic agents in human urine. J Chromatogr B 1996;687(1):3-25. (Pubitemid 27008303)
23. Celsis IVT. Human and Animal Liver S9; 2007. Available from: 〈http://www.celsis.com/media/pdf/filelib/ps-human-animal-s9.pdf〉.
24. Ferraboschi P, Colombo D, Prestileo P. A convenient synthesis of oxandrolone through a regioselective Candida antarctica lipase-catalyzed transformation. Tetrahedron: Asymmetry 2003;14(18):2781-5. (Pubitemid 38435359)
25. Counsell RE, Klimstra PD. Anabolic agents: derivatives of 2-halo 5alpha-androst- 1-ene. J Med Pharm Chem 1962;91:477-83.
26. Klimstra PD, Optionally 17-alkylated-3alpha-methyl- and derivatives thereof, USP Office, editor. USA; 1968.
27. Tavares da Silva EJ, Roleira FMF, Sa e Melo ML, Campos Neves AS, Paixao JA, de Almeida MJ, Silva MR, Andrade LCR. X-ray and deuterium labeling studies on the abnormal ring cleavages of a 5[beta]-epoxide precursor of formestane. Steroids 2002;67(3-4):311-9. (Pubitemid 34150149)
28. Klimstra PD, Optionnally 17-alkylated 17-oxygenated 5alpha-2-en-4-ones and intermediates thereto, USP Office, editor. USA; 1965.
29. Masse R, Bi HG, Ayotte C, Dugal R. Studies on anabolic-steroids. 2. Gas-chromatographic-mass-spectrometric characterization of oxandrolone urinary metabolites in man. Biomed Environ Mass 1989;18(6):429-38. (Pubitemid 19138549)
30. Cruz Silva MM, Riva S, Sá e Melo ML. Regioselective enzymatic acylation of vicinal diols of steroids. Tetrahedron 2005;61(12):3065-73. (Pubitemid 40321106)
31. Horvath A, Skoda-Foldes R, Maho S, Berente Z, Kollar L. Facile ring opening of 2,3-epoxy-steroids with aromatic amines in ionic liquids. Steroids 2006;71(8):706-11. (Pubitemid 43994012)
32. Santos GA, Murray GA, Pujol CA, Damonte EB, Maier MS. Synthesis and antiviral activity of sulfated and acetylated derivatives of 2beta,3alpha-dihydroxy- 5alpha-cholestane. Steroids 2003;68(2):125-32. (Pubitemid 36279162)
33. Karplus M. Vicinal proton coupling in nuclear magnetic resonance. J Am Chem Soc 1963;85(18):2870-1.