Metabolism of methylstenbolone studied with human liver microsomes and the uPA+/+-SCID chimeric mouse model

Autor: Leen Lootens, Koen Deventer, Francesco Botrè, Vinod Nair, Peter Van Eenoo, Michaël Polet, Lore Geldof, Daniel Eichner, Philip Meuleman, Geert Leroux-Roels, Thane Campbell
Rok vydání: 2014
Předmět:
Zdroj: Biomedical Chromatography. 28:974-985
ISSN: 0269-3879
DOI: 10.1002/bmc.3105
Popis: Anti-doping laboratories need to be aware of evolutions on the steroid market and elucidate steroid metabolism to identify markers of misuse. Owing to ethical considerations, in vivo and in vitro models are preferred to human excretion for nonpharmaceutical grade substances. In this study the chimeric mouse model and human liver microsomes (HLM) were used to elucidate the phase I metabolism of a new steroid product containing, according to the label, methylstenbolone. Analysis revealed the presence of both methylstenbolone and methasterone, a structurally closely related steroid. Via HPLC fraction collection, methylstenbolone was isolated and studied with both models. Using HLM, 10 mono-hydroxylated derivatives (U1-U10) and a still unidentified derivative of methylstenbolone (U13) were detected. In chimeric mouse urine only di-hydroxylated metabolites (U11-U12) were identified. Although closely related, neither methasterone nor its metabolites were detected after administration of isolated methylstenbolone. Administration of the steroid product resulted mainly in the detection of methasterone metabolites, which were similar to those already described in the literature. Methylstenbolone metabolites previously described were not detected. A GC-MS/MS multiple reaction monitoring method was developed to detect methylstenbolone misuse. In one out of three samples, previously tested positive for methasterone, methylstenbolone and U13 were additionally detected, indicating the applicability of the method.
Databáze: OpenAIRE
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