Copyright@ Mohammed Al Maadheed | Biomed J Sci & Tech Res | BJSTR. MS.ID.007000. 35212 Research Article ISSN: 2574 -1241 DOI: 10.26717/BJSTR.2022.44.007000 A Reproducible Method for the Identification of Methandrostenolone Metabolites Using a Humanized Liver Rodent Model Maneera AlJaber 1 , Wadha Abushreeda 1 , Asmaa Raees 1 , Ariadni Vonaparti 1 , Suhail Kraiem 1 , Shaikha AlSowaidi 1 , Khadija Saad 1 , Garry Lund 2 , Svetlana Sapelnikova 2 , David Abraham 3 , David Morgan 4 , Costas Georgakopoulos 1 , Norman Kneteman 4,5 , Vidya Mohamed-Ali 1 and Mohammed Al Maadheed 1 * 1 Anti-Doping Laboratory Qatar, Sports City Road, Qatar 2 KMT Hepatech lnc. 11421 Saskatchewan Drive Edmonton, Canada 3 Division of Medicine, Royal Free Campus, University College London, UK 4 University of Bristol, University Walk, UK 5 Division of Transplantation Surgery, University of Alberta, Canada *Corresponding author: Mohammed Al Maadheed, Anti-Doping Laboratory Qatar, Sports City Road, Doha, Qatar ARTICLE INFO ABSTRACT Received: May 12, 2021 Published: May 25, 2022 Citation: Maneera AlJaber, Wadha Abushreeda, Asmaa Raees, Ariadni Von- aparti, Mohammed Al Maadheed, et al., A Reproducible Method for the Identifica- tion of Methandrostenolone Metabolites Using a Humanized Liver Rodent Mod- el. Biomed J Sci & Tech Res 44(1)-2022. BJSTR. MS.ID.007000. Anabolic Androgenic Steroids (AAS), despite them being prohibited, are the most prevalent sport performance enhancing substances used by competing athletes. Identification of stable metabolites of AAS, such as methandrostenolone, in humans is required as reliable markers of their use. However, ethical issues make such studies difficult in human subjects. Therefore, the current study tested the hypothesis that a humanized urokinase Plasminogen Activator-Severe combined Immunodeficient murine model (uPA+/+-SCID mice) administered methandrostenolone at pharmacological concentrations, following both single and multiple dosing, is able to generate all its previously reported human metabolites. The hepatic mRNA expression of human Phase 1 enzymes was significantly altered in the drug treated chimeric mice, with an increase in aldehyde dehydrogenase activity being apparent in the serum. Following UHPLC/HRMS and GC/MSMS analysis of the urine, data showed the presence of all expected metabolites, including the long-term stable species, in the drug-treated, but not vehicle-treated, cohort. None of these changes were seen in the non-chimeric mice. Thus, this report provides further support for the reliability and sensitivity of uPA+/+-SCID mouse model for the identification of transient and stable metabolites of orally administered AAS in humans, especially following multiple dosing. The application of non-targeted metabolomics to samples derived from this model is likely to lead to the identification of novel metabolites of emerging, orally ingested anabolic agents.