Direct detection of the internal acyl migration reactions of benzoic acid 1-O-acylglucuronide by 13C-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 13C-labeling and nuclear magnetic resonance (NMR) spectroscopy has been developed 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, the glucuronide showed apparent first-order degradation kinetics (T1/2, 125 min), and concurrent and sequential appearance of 2-, 3- and 4-O-acyl isomers as both alpha- and beta-anomers was observed. The isomeric glucuronides were identified by two-dimensional NMR of the reaction mixture. The direct approach using 13C-labeling and NMR could also provide insights into the reactivities of other labile drug acylglucuronides and their isomeric glucuronides.
Akira
K
K
School of Pharmacy, Tokyo University of Pharmacy and Life Science, Japan. akira@ps.toyaku.acjp
Taira
T
T
Shinohara
Y
Y
D001565:Benzoates / Q000737:chemistry*; D019817:Benzoic Acid; D002247:Carbon Isotopes; D005965:Glucuronates / Q000737:chemistry*; D007553:Isotope Labeling; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D011485:Protein Binding; D012680:Sensitivity and Specificity; D013237:Stereoisomerism
D001565:Benzoates; D002247:Carbon Isotopes; D005965:Glucuronates; D019817:Benzoic Acid