Kinetics and mechanism of degradation of cefotaxime sodium in aqueous solution

The degradation kinetics and mechanism of a potent new cephalosporin, cefotaxime sodium, in aqueous solution were investigated at pH 0-10 at 25 degrees and an ionic strength of 0.5. The degradation rates were determined by high-pressure liquid chromatography and were observed to follow pseudo first-order kinetics with respect to cefotaxime sodium concentration. The data suggested that the rate of degradation was influenced significantly by solvolytic, hydrogen ion, and hydroxide ion catalysis. No primary salt effects were observed in the acid or neutral regions; however, a positive salt effect was observed at pH 8.94. Buffer catalysis due to the buffer species employed was not seen during the kinetic studies. The pH-rate profile at 25 degrees indicated that the maximum stability of cefotaxime sodium occurred in the pH 4.5-6.5 region. In aqueous solution, cefotaxime was shown to degrade by two parallel reactions: de-esterification at the C-3 position and beta-lactam cleavage. Good agreement between the theoretical pH-rate profile and the experimental data support the proposed degradation process.