HPLC–MS Profiling and Structural Identification of [~(14)C]?Diclofenac Metabolites in Mouse Bile

摘要

Biliary metabolites present at 6 h post-dose following a single oral dose of [~(14)C]-diclofenac (10 mg kg~(?1)) to male bile duct-cannulated C57BL/6 J mice were profiled and identified. Over the 6 h duration of the study ~19.5 % of the administered radioactivity was excreted into the bile as either [~(14)C]-diclofenac or metabolites. When profiled using HPLC with online radiodetection, the presence of at least 13 radiolabelled components was indicated. These compounds were shown, by consecutive reaction mass spectrometry, to comprise a range of hydroxylated metabolites conjugated to either taurine, glucose and/or glucuronic acid. Both phenolic and acylglucuronide-containing metabolites were observed. The confirmation of the presence of these glucuronide conjugates in mouse bile may have important consequences in the light of emerging theories concerning the role of bacterial glucuronidases for the GItract toxicity of NSAIDs such as diclofenac.