Abstract
The stability of clavulanic acid in aqueous solutions has been investigated over a pH range of 3.15 to 10.10 at 35°C and at an ionic strength of 0.5. The changes in the concentration of intact clavulanic acid in buffer solutions were determined by reversed phase HPLC with UV-detection using a mobile phase containing tetrabutylammonium bromide. The observed degradation rates at various pH's were found to follow pseudo-first-order kinetics, and were significantly affected by catalysis due to buffer salts. The catalytic rate constants were estimated at three different concentrations of buffer systems. The pH vs. rate profiles obtained from non-buffer-catalyzed rate constants, kpH, revealed that the degradation in alkaline solutions proceeded, as a whole, about 10 times faster than in acidic media, and maximal stability was attained at pH 6.39. The Arrhenius activation energies at pH 3.94, 6.67, and 8.74 were estimated as 19.0, 14.7, and 18.3 kcal/mol, respectively.
