FACTORS AFFECTING THE DEAMIDATION OF VANCOMYCIN IN AQUEOUS-SOLUTIONS

The degradation kinetics of vancomycin were studied in aqueous solutio ns at 50 degrees C. The deamidation of 2 mM vancomycin solutions maint ained between pH 3 and 9.8 followed pseudo-first order kinetics over s everal half-lives. The amine pK(a) values of vancomycin were titrated by H-1-NMR at 50 degrees C. These values were calculated to be 6.84 an d 7.82 for pK(a2) and pK(a3), respectively. These are predictably lowe r than the values 7.75 and 8.89 which were reported in the literature for the amine pK(a) values at 25 degrees C. Rate constants obtained fr om curve fitting the pH-rate profile for vancomycin to the experimenta lly observed data indicate that the reactivity of vancomycin toward de amidation in the region of pH 6-9 is influenced by its ionic state. Th e sites of ionization appear to be well removed from the reaction cent er, suggesting that the ionic state is influencing the solution confor mation of vancomycin and subsequently affecting its degradation rate.