HPLC–MS Profiling and Structural Identification of [14C]-Diclofenac Metabolites in Mouse Bile |
| |
Authors: | Sunil Sarda Elizabeth A Partridge Kathryn Pickup Alan McCarthy Ian D Wilson |
| |
Institution: | 1. Drug Metabolism and Pharmacokinetics IM, AstraZeneca, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UK 4. Discovery Sciences IM, AstraZeneca, 52F44, Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UK 2. Global Safety Assessment, AstraZeneca, Alderley Park, Macclesfield, Cheshire, SK10 4TG, UK 3. Department of Surgery and Cancer, Imperial College, Exhibition Rd, South Kensington, London, SW7 2AZ, UK
|
| |
Abstract: | Biliary metabolites present at 6 h post-dose following a single oral dose of 14C]-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 14C]-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 GI-tract toxicity of NSAIDs such as diclofenac. |
| |
Keywords: | |
本文献已被 SpringerLink 等数据库收录! |
|