Stability of Flomoxef in Aqueous Solution and in Intravenous Admixture of 5% Glucose Infusion

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Abstract
The stability of flomoxef, an oxacephem antibiotic, was studied in various buffer solutions and intravenous admixtures. Degradation in buffer solutions at 25.degree. C and ionic strength of 0.6 obeyed pseudo first-order kinetics. Excluding the effects of buffer salts by extrapolation to zero buffer concentration, pH-rate profile was obtained. From the general rate law as a function of hydrogen ion concentration, t0.9 at pH 4-8 was predicted to be 32-37 h. The apparent activation energies at pH 3, 6 and 9 were 12.6, 20.0 and 27.2 kcal mol-1, respectively. Studies on stability in various infusions and 5% glucose admixtures indicated the acceleration of degradation in amino acids infusions, admixtures of aminophylline, tegafur and 5-fluorouracil injections. The interactions of flomoxef with tegafur and/or 5-fluorouracil injections were studied in carbonate buffer with or without glucose at pH 9.0. The results suggested that the reaction of flomoxef with glucose predominated over those with ingredients of 5-fluorouracil or tegafur injections, namely tromethamine or carbonate molecules. Thus, the injections with high pH are incompatible with flomoxef and related antibiotics, especially in large volume injections containing glucose as well as another carbohydrate. But if sufficient dilution of active components or adjustment of pH of the admixtures below 6 could be attained, one can use in safe and useful even the above incompatible combinations.