Identification of Urinary Metabolites of Befunolol in Dog and Man principally by Mass Spectrometry

Abstract

Urinary metabolites of dogs and humans receiving befunolol (BF) were isolated by column chromatography on Amberlite XAD-2 resin and thin layer chromatography on silica gel. Unchanged BF and the following ten metabolites containing five glucuronides were identified in the dog by mass spectrometry (including GC/MS) : I, II, III, IV, V, O-glucuronide of 7-side-chain of BF (BF-7-OG), O-glucuronide of 7-side-chain of I (I-7-OG), O-glucuronide of 2-side-chain of I (I-2-OG), O-glucuronide of phenolic OH of III (III-4-OG) and O-glucuronide of phenolic OH of IV (IV-4-OG). The following five substances were detected in humans : BF, I, BF-7-OG, I-7-OG and I-2-OG. Neither III-4-OG, a major metabolite in the dog, nor its aglycone (III) was detected in humans, suggesting a species difference in the metabolic pathway of BF.