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This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: clinchem.2008.119396v1 55/10/1783    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Google Scholar Articles by Lootens, L. Articles by Delbeke, F. T. PubMed PubMed Citation Articles by Lootens, L. Articles by Delbeke, F. T.

uPA^+/+-SCID Mouse with Humanized Liver as a Model for In Vivo Metabolism of Exogenous Steroids: Methandienone as a Case Study

¹ Doping Control Laboratory, Zwijnaarde, Belgium;² Center for Vaccinology, Ghent University and Hospital, Ghent, Belgium.

^aAddress correspondence to this author at: Ghent University, Department of Clinical Chemistry, Microbiology and Immunology, Technologiepark 30, B-9052, Zwijnaarde, Belgium. Fax 32-09-3313299; e-mail Leen.Lootens{at}UGent.be.

Background: Adequate detection of designer steroids in the urine of athletes is still a challenge in doping control analysis and requires knowledge of steroid metabolism. In this study we investigated whether uPA^+/+-SCID mice carrying functional primary human hepatocytes in their liver would provide a suitable alternative small animal model for the investigation of human steroid metabolism in vivo.

Methods: A quantitative method based on liquid chromatography–tandem mass spectrometry (LC-MS/MS) was developed and validated for the urinary detection of 7 known methandienone metabolites. Application of this method to urine samples from humanized mice after methandienone administration allowed for comparison with data from in vivo human samples and with reported methandienone data from in vitro hepatocyte cultures.

Results: The LC-MS/MS method validation in mouse and human urine indicated good linearity, precision, and recovery. Using this method we quantified 6 of 7 known human methandienone metabolites in the urine of chimeric mice, whereas in control nonchimeric mice we detected only 2 metabolites. These results correlated very well with methandienone metabolism in humans. In addition, we detected 4 isomers of methandienone metabolites in both human and chimeric mouse urine. One of these isomers has never been reported before.

Conclusions: The results of this proof-of-concept study indicate that the human liver–uPA^+/+-SCID mouse appears to be a suitable small animal model for the investigation of human-type metabolism of anabolic steroids and possibly also for other types of drugs and medications. .

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