Overlapping ionization constants for cefotaxime.

The attribution of three ionization constants (2.1, 3.4, and 10.9) for cefotaxime has been made, based on potentiometric titration and UV absorption data simultaneously. Two overlapping constants were found (2.1 and 3.4) and attributed to the carboxyl group in the 4 position and to the aminothiazole nucleus, respectively.

Degradation kinetics in aqueous solution of cefotaxime sodium, a third-generation cephalosporin.

The degradation kinetics of a 3- acetoxymethylcephalosporin , cefotaxime sodium salt, in aqueous solution investigated by HPLC under different conditions (pH, ionic strength, temperature) and using different buffers. The scheme of degradation involves a cleavage of the beta-lactam nucleus and the deacetylation of the side chain. In highly acidic medium, the deacetylated derivative is easily converted to the lactone. The degradation rate constants were calculated at three pH values (1.9, 4.0, and 9.0) by measuring the residual cephalosporin and the main decomposition products. The degradation pathway is both supported by the results of a primary salt effect and by the agreement between the theoretical pH-rate profile and the experimental values. In the pH range from 3.0 to 7.0, the main process is a slow water-catalyzed or spontaneous cleavage of the beta-lactam nucleus with intramolecular participation of the side chain amido fraction in the 7-position. In alkaline or strongly acidic medium, the hydrolysis is a base- or acid-catalyzed reaction. Of the buffer systems investigated, carbonate buffer (pH 8.5) and borate buffers (pH 9.5 and 10.0) are found to increase the degradation rates, while acetate buffer decreases the degradation rates. The apparent activation energies determined at different pH values are compatible with a solvolysis mechanism and similar to those previously given in the literature for other cephalosporins. Cefotaxime in aqueous solution is slightly less stable than the main cephalosporin derivatives, despite its high resistance to the beta-lactamases and its remarkable biological activity.