Chemical Compatibility of Cefmetazole Sodium with Ranitidine Hydrochloride During Simulated Y-Site Administration

Abstract

The stability of cefmetazole sodium and ranitidine hydrochloride was studied under conditions simulating administration via a Y-injection site into a primary infusion line.

Cefmetazole sodium was reconstituted with both 0.9% sodium chloride injection (50 mL or 100 mL) and 5% dextrose injection (50 mL) to produce premixing concentrations of cefmetazole 10 and 20 mg/mL. Ranitidine hydrochloride injection was diluted with 50 mL 0.9% sodium chloride injection to give premixing concentrations of ranitidine 1 mg/mL. To simulate Y-site administration, 2 mL of cefmetazole was mixed with 2 mL of ranitidine in a 10-mL glass test tube. All study mixtures were prepared in triplicate and stored at room temperature (22–23°C) under normal fluorescent room lighting. Samples of these admixtures were inspected for visual changes and tested for pH. The concentrations of two drugs were immediately determined by stability-indicating high-performance liquid chromatographic assay methods after mixing and at 1, 2, and 4 hours. No visual changes were observed. The pH in the admixtures was influenced by concentrations of the two drugs. The pH of each single-drug solution did not change during the study period. On the other hand, the pH of any admixtures of cefmetazole and ranitidine solutions prepared with 0.9% sodium chloride or 5% dextrose injection, decreased. Cefmetazole in any of the admixtures with ranitidine retained greater than 95% of its original concentration for 4 hours. Ranitidine in the admixture containing 5 mg/mL cefmetazole in 0.9% sodium chloride retained more than 95% of its original concentration for 4 hours, but ranitidine in the admixture containing 10 mglmL cefmetazole in both 0.9% sodium chloride and 5% dextrose retained less than 90% of its original concentration after 4 hours. The stability of ranitidine in the admixture decreased as the concentration of cefmetazole increased.

In the admixtures containing 0.5 mg/mL ranitidine and 5 mg/mL cefmetazole, the concentrations of two dnugs varied by less than 10% throughout the study period. Solutions containing 1 mg/mL ranitidine may be coadministered with solutions of 10 mg/mL cefmetazole, but not 20 mg/mL, via Y-injection site. Either cefmetazole solution may be coadministered with the ranitidine solution in a situation in which the combination contact time is less than 2 hours.