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Detection and characterization of a new metabolite of 17 α-methyltestosterone

(2009) DRUG METABOLISM AND DISPOSITION. 37(11). p.2153-2162
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Abstract
The misuse of the anabolic steroid methyltestosterone is currently routinely monitored in doping control laboratories by gas chromatography-mass spectrometry (GC-MS) of two of its metabolites: 17 alpha-methyl-5 beta-androstane-3 alpha,17 beta-diol and 17 alpha-methyl-5 alpha-androstane-3 alpha,17 beta-diol. Because of the absence of any easy ionizable moiety, these metabolites are poorly detectable using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with electrospray ionization (ESI). In this study, the metabolism of methyltestosterone has been reinvestigated by the use of a precursor ion scan method in LC-ESI-MS/MS. Two metabolites have been detected using this method. Both compounds have been confirmed in postadministration urine samples of an urokinase plasminogen activator-severe combined immunodeficiency (uPA-SCID) mouse with humanized liver and were characterized by LC-MS/MS and GC-MS using both quadrupole and time of flight analyzers. From the detailed study of the fragmentation, these metabolites were proposed to be epimethyltestosterone and a dehydrogenated compound. Epimethyltestosterone has previously been described as a minor metabolite, whereas the occurrence of the oxidized metabolite has not been reported. Comparison with the synthesized reference revealed that the structure of the dehydrogenated metabolite is 6-ene-epimethyltestosterone. A selected reaction monitoring method including three transitions for each metabolite has been developed and applied to samples from an excretion study and to samples declared positive after GC-MS analysis. 6-Ene-epimethyltestosterone was found in all samples, showing its applicability in the detection of methyltestosterone misuse.

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Chicago
Pozo Mendoza, Oscar Juan, Peter Van Eenoo, Koen Deventer, Leen Lootens, Wim Van Thuyne, Maria Parr, Wilhelm Schanzer, et al. 2009. “Detection and Characterization of a New Metabolite of 17 Α-methyltestosterone.” Drug Metabolism and Disposition 37 (11): 2153–2162.
APA
Pozo Mendoza, O. J., Van Eenoo, P., Deventer, K., Lootens, L., Van Thuyne, W., Parr, M., Schanzer, W., et al. (2009). Detection and characterization of a new metabolite of 17 α-methyltestosterone. DRUG METABOLISM AND DISPOSITION, 37(11), 2153–2162.
Vancouver
1.
Pozo Mendoza OJ, Van Eenoo P, Deventer K, Lootens L, Van Thuyne W, Parr M, et al. Detection and characterization of a new metabolite of 17 α-methyltestosterone. DRUG METABOLISM AND DISPOSITION. 2009;37(11):2153–62.
MLA
Pozo Mendoza, Oscar Juan, Peter Van Eenoo, Koen Deventer, et al. “Detection and Characterization of a New Metabolite of 17 Α-methyltestosterone.” DRUG METABOLISM AND DISPOSITION 37.11 (2009): 2153–2162. Print.
@article{843152,
  abstract     = {The misuse of the anabolic steroid methyltestosterone is currently routinely monitored in doping control laboratories by gas chromatography-mass spectrometry (GC-MS) of two of its metabolites: 17 alpha-methyl-5 beta-androstane-3 alpha,17 beta-diol and 17 alpha-methyl-5 alpha-androstane-3 alpha,17 beta-diol. Because of the absence of any easy ionizable moiety, these metabolites are poorly detectable using liquid chromatography-tandem mass spectrometry (LC-MS/MS) with electrospray ionization (ESI). In this study, the metabolism of methyltestosterone has been reinvestigated by the use of a precursor ion scan method in LC-ESI-MS/MS. Two metabolites have been detected using this method. Both compounds have been confirmed in postadministration urine samples of an urokinase plasminogen activator-severe combined immunodeficiency (uPA-SCID) mouse with humanized liver and were characterized by LC-MS/MS and GC-MS using both quadrupole and time of flight analyzers. From the detailed study of the fragmentation, these metabolites were proposed to be epimethyltestosterone and a dehydrogenated compound. Epimethyltestosterone has previously been described as a minor metabolite, whereas the occurrence of the oxidized metabolite has not been reported. Comparison with the synthesized reference revealed that the structure of the dehydrogenated metabolite is 6-ene-epimethyltestosterone. A selected reaction monitoring method including three transitions for each metabolite has been developed and applied to samples from an excretion study and to samples declared positive after GC-MS analysis. 6-Ene-epimethyltestosterone was found in all samples, showing its applicability in the detection of methyltestosterone misuse.},
  author       = {Pozo Mendoza, Oscar Juan and Van Eenoo, Peter and Deventer, Koen and Lootens, Leen and Van Thuyne, Wim and Parr, Maria and Schanzer, Wilhelm and Sancho, Juan and Hernandez, Felix and Meuleman, Philip and Leroux-Roels, Geert and Delbeke, Frans},
  issn         = {0090-9556},
  journal      = {DRUG METABOLISM AND DISPOSITION},
  language     = {eng},
  number       = {11},
  pages        = {2153--2162},
  title        = {Detection and characterization of a new metabolite of 17 \ensuremath{\alpha}-methyltestosterone},
  url          = {http://dx.doi.org/10.1124/dmd.109.028373},
  volume       = {37},
  year         = {2009},
}

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