Stability of frozen solutions of cefamandole nafate

The chemical, microbiological and visual stability of frozen solutions of cefamandole nafate was studied. Solutions of cefamandole nafate were prepared by diluting 1 g of drug with 3 ml of Water for Injection, USP, or 0.9% Sodium Chloride Injection, USP, or 5% Dextrose Injection, USP (i.m. dilutions); or with 50 or 100 ml of the latter two diluents (i.v. dilutions). Stability of samples stored in glass and polyvinyl chloride plastic containers for up to 52 weeks at -10 and -20 C was measured by microbiologic, polarographic, iodometric, nephelometric and chromatographic assay and pH was measured. In mice, LD50 tests were performed using the i.m. dilutions. I.M. dilutions of cefamandole nafate were stable for 52 weeks when stored at -20 C; at -10 C, however, some samples did not freeze completely and were turbid when thawed. I.V. dilutions were stable for 26 weeks when stored at -20 C. I.V. dilutions with D5W stored at -10 C developed a transient haze. A gradual decrease in pH, which was a function of storage time, was noted for the frozen solutions. Six months of freezing did not alter the LD50 in mice. Solutions of cefamandole nafate are stable for at least 26 weeks when stored at -20 C in glass or PVC containers.