Catalytic Effect of Buffers on Degradation of Imipenem (N-Formimidoylthienamycin) in Aqueous Solution

概要

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The catalytic effect of various buffer systems on the degradation of imipenem (N-formimidoylthienamycin) in aqueous solution at 35℃ and at an ionic strength of 0.5 mol・dm^<-3> has been studied. Changes in the concentration of intact imipenem in the solutions were determined by reverse-phase high-performance liquid chromatography (HPLC) with UV-detection. The observed degradation rates at various pH's were found to follow pseudo-first-order kinetics with regard to imipenem concentrations (2×10^<-4> mol・dm^<-3>) and were significantly influenced by general acid and general base catalysis. Of the buffer systems employed in the kinetic studies the citrate buffer and borate buffer systems showed the greatest catalytic effects. The pH-rate profile obtained from non-buffer-catalyzed rate constants, k_<pH>, showed a minimum at a pH of 6.40. The calculated theoretical pH-rate profile and the experimental points coincide, thus supporting the hypothesis presented concerning the reactions involved in the degradation of imipenem in solution. The Arrhenius activation energies at pH 4.21,6.58 and 8.64 were estimated as 12.47,15.22 and 17.49 kcal/mol. respectively.
社団法人日本薬学会の論文
1991-04-25