DIRECT-DETECTION OF THE INTERNAL ACYL MIGRATION REACTIONS OF BENZOIC-ACID 1-O-ACYLGLUCURONIDE BY C-13-LABELING AND NUCLEAR-MAGNETIC-RESONANCE SPECTROSCOPY

1-O-Acyl-beta-D-glucopyranuronates can undergo irreversible binding to proteins mainly through internal acyl migration reactions, which may have toxicological significance. A new method based on the C-13-labeli ng and nuclear magnetic resonance (NMR) spectroscopy has been develope d to study the reactivity of the 1-O-acyl-beta-D-glucopyranuronate of benzoic acid. In phosphate buffer (pH 7.4) solution at 37 degrees C, t he glucuronide showed apparent first-order degradation kinetics (T-1/2 , 125 min), and concurrent and sequential appearance of 2-, 3- and 4-O -acyl isomers as both alpha- and beta-anomers was observed. The isomer ic glucuronides were identified by two-dimensional NMR of the reaction mixture. The direct approach using C-13-labeling and NMR could also p rovide insights into the reactivities of other labile drug acylglucuro nides and their isomeric glucuronides. (C) 1997 Elsevier Science Inc.