The metabolism of some steroids in the horse.

This thesis has been mainly concerned with the determination of the overall urinary excretion and the characterization of the neutral urinary metabolites of dexamethasone, testosterone, 1-dehydrotestosterone and 19-nortestosterone after intramuscular administration to castrated horses (ponies and thoroughbreds). The percentages of the free and the conjugated steroids were determined after solvent extraction and Sephadex LH-20 column chromatography. The urinary steroids were extracted by Amberlite XAD-2 and separated into glucuronides and sulphoconjugates by Sephadex LH-20 chromatography. After enzyme hydrolysis and solvolysis respectively, the freed steroids were fractionated on Kieselgel H columns and after derivatization as their trimethylsilyl ethers or methoxime-trimethylsilyl ethers, were analysed by combined gas chromatography-mass spectrometry. The metabolites of dexamethasone were identified by microchemical reactions and thin-layer chromatography. Results of the analysis have shown that in general the pathways of biotransformation (Phase I and Phase II) of these steroids in the equine castrate were qualitatively similar to those previously reported for other species. However, the quantitative differences in the excretion and relative importance of these pathways are attributed to the effects of species difference and the structural modification of the steroids. Epimerization at C-17 with stereoselective conjugation to glucuronic acid, stereo-selective reduction of the Delta4-3-oxo group with the formation of 3beta,5alpha-isomer, stereoselective conjugation of the 17beta-hydroxyl group to sulphuric acid and the hydroxylation at C-16 were major transformations observed for the anabolic steroids. 6-Hydroxylation and reduction of the 20-ketone were the major transformations for dexamethasone. On the basis of the results obtained from this work it is now possible to develop specific gc-ms methods to confirm the administration of these steroids to horses