کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2028212 1070402 2010 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Comparative in vitro metabolism of the ‘designer’ steroid estra-4,9-diene-3,17-dione between the equine, canine and human: Identification of target metabolites for use in sports doping control
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Comparative in vitro metabolism of the ‘designer’ steroid estra-4,9-diene-3,17-dione between the equine, canine and human: Identification of target metabolites for use in sports doping control
چکیده انگلیسی

Effective detection of the abuse of androgenic-anabolic steroids in human and animal sports often requires knowledge of the drug's metabolism in order to target appropriate urinary metabolites. ‘Designer’ steroids are problematic since it is difficult to obtain ethical approval for in vivo metabolism studies due to a lack of a toxicological profile.In this study, the in vitro metabolism of estra-4,9-diene-3,17-dione is reported for the first time. This is also the first study comparing the metabolism of a designer steroid in the three major species subject to sport's doping control; namely the equine, canine and human. In order to allow the retrospective analysis of sample testing data, the use of a high-resolution (HR) accurate-mass Thermo LTQ-Orbitrap LC–MS instrument was employed for metabolite identification of underivatised sample extracts. The full scan HR–LC–MS Orbitrap data was complimented by several further experiments targeted at elucidating more detailed structural information for the most abundant metabolites. These included; HR–LC–MS/MS of the underivatised metabolites, functional group selective chemical derivatisation followed by full scan HR–LC–MS, enzyme inhibition experiments and full scan electron ionization GC–MS analysis of methoxyamine–trimethylsilyl derivatives.The major metabolite detected in all species, and therefore the most suitable candidate for screening of estra-4,9-diene-3,17-dione abuse, was proposed to be an isomer of 17-hydroxy-estra-4,9-dien-3-one. Less significant metabolic pathways in all species included hydroxylation and reduction followed by hydroxylation. Reductive metabolism in the canine was less significant than in the other two species, while the equine was unique in producing a di-reduced metabolite (proposed to be an isomer of estra-4,9-diene-3,17-diol) and also relatively large quantities of d-ring hydroxy and hydroxy-reduced metabolites.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Steroids - Volume 75, Issue 10, October 2010, Pages 643–652
نویسندگان
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