Frable, RA; Klink, PR; Engel, GL; Mundell, EE
The stability of cefamandole nafate injection in various parenteral solutions and with secondary additives was investigated.
Solutions of cefamandole nafate injection in the following. concentrations were prepared: (1) 285 mg/ml cefamandole activity in nine intramuscular solutions; (2) 2 or 20 mg/ml; or both, in 28 intravenous solutions; (3)2 and 5 mg/ml in peritoneal dialysis fluid (PDF) concentrates with 30 and 50% dextrose; (4) 2, 20, and 100 mg/ml with tobramycin sulfate, gentamicin sulfate, calcium gluceptate, and calcium gluconate; and 0) concentrations up to 285 mg/ml with various concentrations Tof lidocaine hydrochloride. The solutions were stored at 5 and A 25 °C and evaluated visually for incompatibility. Stability of cefamandole nafate was determined periodically by polarographic or turbidimetric assay. The extent of hydrolysis of the formyl ester of cefamandole in some solutions was also studied using high-pressure liquid chromatography.
Greater than 90% cefamandoie potency was retained for at least three days at 25 °C and 10 days at 5 °C in all parenteral solutions except in 2 mg/ml in 5% dextrose, 5% dextrose and 0.15% potassium chloride, 5% dextrose and 0.45% sodium chloride, Plasma-Lyte, and 0.9% sodium chloride injections. Visual incompatibilities were observed in acetated Ringer's, 5% dextrose and 0.15% potassium chloride, lonosol B in 5% dextrose, Isolyte E with 5% dextrose, Isolyte M with 5% dextrose, Plasma-Lyte, Ringer's, and lactated Ringer's injections. Cefamandoie nafate was incompatible with all secondary additives except with certain concentrations of lidocaine hydrochloride. Cefamandoie nafate 2 mg/ml was compatible with the PDF concentrates for 24 hours at 25 °C. The dextrose content and the pHdf the parenteral solutions influenced the rate and extent of hydrolysis of the formyl ester of cefamandole.
Cefamandole nafate was stable and compatible in 11 of the 37 parenteral solutions studied for at least three days at 25 °C and. 10 days at 5 °C. Considering the potential for microbial growth, however, storage limits of 24 and 96 hours at 25 and 5 °C, respectively, are recommended.