Kinetic Study of the Degradation of Cefotiam Dihydrochloride in Aqueous Solution and of the Reaction with Aminoglycosides

Abstract

The kinetics of the degradation of cefotiam in aqueous solution was studied at 25°C and an ionic strength of 0.6 over the pH range of 2 to 12. The degradation was a pseudo first order reaction in this pH range. The rate-pH profile showed a characteristic maximum near the isoelectric point of cefotiam (pH 5.8). The optimal pH of an aqueous solution of cefotiam dihydrochloride for stability was calculated to be 8.0. The degradation pathways were shown to involve spontaneous hydrolysis of four ion species and hydroxide ion-catalyzed hydrolysis of the monoanion. Aminoglycosides accelerated the degradation of cefotiam by a pseudo second order reaction. From analysis of the rate-pH profile of the second order rate constants of these aminoglycosides, it appeared that the reaction was substantially a third order reaction with regards to cefotiam, aminoglycoside and hydroxide ion. Therefore, the combined use of cefotiam and aminoglycosides should be avoided at alkaline pH and/or at high concentration.