Metabolism of methyltestosterone in the greyhound

Gas chromatography/mass spectrometry and selective derivatisation techniques have been used to identify urinary metabolites of methyltestosterone following oral administration to the greyhound. Several metabolites were identified including reduced, mono‐, di‐ and trihydroxylated steroids. The major metabolites observed were 17α‐methyl‐5β‐androstane‐3α‐17β‐diol, 17α‐methyl‐5β‐androstane‐3α,16α,17β‐triol, and a further compound tentatively identified as 17α‐methyl‐5z‐androstane‐6z,17β‐triol. The most abundant of these was the 17α‐methyl‐5β‐androstane‐3α,16α,17β‐triol. This metabolite was identified by comparison with a reference standard synthesised using a Grignard procedure and characterised using trimethylsilyl (TMS) and acetonide‐TMS derivatisation techniques. There did not appear to be any evidence for 16β‐hydroxylation as a phase I metabolic transformation in the greyhound. However, significant quantities of 16α‐hydroxy metabolites were detected. Selective enzymatic hydrolysis procedures indicated that the major metabolites identified were excreted as glucuronic acid conjugates. Metabolic transformations observed in the greyhound have been compared with those of other mammalian species and are discussed here. Copyright © 2009 John Wiley & Sons, Ltd.