Factors affecting the deamidation of vancomycin in aqueous solutions

The degradation kinetics of vancomycin were studied in aqueous solutions at 50°C. The deamination of 2 mM vancomycin solutions maintained between pH 3 and 9.8 followed pseudo-first order kinetics over several half-lives. The amine pKa values of vancomycin were titrated by 1H-NMR at 50°C. These values were calculated to be 6.84 and 7.82 for pKa2 and pKa3, respectively. These are predictably lower than the values 7.75 and 8.89 which were reported in the literature for the amine pKa values at 25°C. Rate constants obtained from curve fitting the pH-rate profile for vancomycin to the experimentally observed data indicate that the reactivity of vancomycin toward deamidation in the region of pH 6–9 is influenced by its ionic state. The sites of ionization appear to be well removed from the reaction center, suggesting that the ionic state is influencing the solution conformation of vancomycin and subsequently affecting its degradation rate.