Acyl-Glucuronide ReactivityIn vitro Metabolism
• Stability and reactivity of acyl-glucuronide metabolites
• No need for synthesised metabolite
• UPLC/HR-MS detection
Although glucuronide conjugation is most often considered as a detoxifying metabolic route, acyl-glucuronide conjugates, formed in the presence of carboxylic acid group, may cause toxicity by covalent binding to proteins. Liability for toxicity of an acyl glucuronide metabolite may be evaluated by measuring the rate of acyl-migration, i.e. formation of isomeric acyl-glucuronides and eventually formation of reactive aldehyde-isomer. This method is a valuable tool for assessing acyl-glucuronide reactivity without the need for synthetised glucuronide metabolites. In addition to acyl glucuronide conjugates, also formation of even more reactive Acyl CoA-conjugates or other related conjugates (glycine, taurine, carnitine) may be investigated by our methods.