Stability of Cefazolin Sodium in Four Heparinized and Non-Heparinized Dialysate Solutions at 38°C

Abstract

Background

Intraperitoneal administration of antibiotics is often required in the treatment of peritoneal dialysis-associated peritonitis. Extended use and heating may affect drug stability. The objective of our study was to determine the stability of cefazolin sodium (125 mg/L and 500 mg/L) in heparinized and non-heparinized dextrose-containing peritoneal dialysis solution (Dianeal PD-2; Baxter Healthcare, Deerfield, Illinois, USA) containing 1.5%, 2.5%, or 4.25% dextrose, or 7.5% icodextrin, the new colloid formulation (Extraneal; Baxter), at 38°C for 4 days.

Methods

Three poly-vinyl chloride containers of each dialysis fluid were stored at 38°C for 4 days. Samples were taken after the bags were mixed and allowed to stand for 2 minutes. Two 500-μL samples were collected from each bag at hours 0, 12, 24, 36, 48, 60, 72, 84, and 96. Samples were then analyzed by high-performance liquid chromatography (HPLC) in our laboratory. In order to establish the stability-indicating nature of the method, drugs 1.0 mg/mL, vehicles, and their mixtures were subjected to a forced degradation. This is done by acid (2.0 mol/L HCl) and base (2.0 mol/L NaOH) hydrolysis, oxidation (H₂O₂ 0.3%), and heat at 80°C. Samples were analyzed every 30 minutes until approximately 25% of the drug's peak disappeared. The drug was considered stable if its concentration exceeded 90% of the original.

Results

For all Dianeal PD-2 peritoneal dialysis solution containing 1.5%, 2.5%, and 4.25% dextrose, cefazolin sodium was considered stable at 38°C for 60 hours at low cefazolin concentrations (125 mg/L), both with and without heparin, and for 48 hours at high cefazolin concentrations (500 mg/L). Cefazolin sodium was considered stable at 38°C in icodextrin for 48 hours at low cefazolin concentrations in heparinized and non-heparinized solutions, and at high concentrations only in non-heparinized dialysate, not in heparinized dialysate. Cefazolin sodium was considered stable at 38°C in icodextrin for 60 hours at high concentrations when heparinized.

Conclusion

Cefazolin sodium was stable in all four non-heparinized dialysate fluids for at least 48 hours at 38°C. In heparinized icodextrin dialysate, high concentrations of cefazolin sodium were not stable for extended periods of time. Extended use and heating of dialysate containing cefazolin may adversely affect patient outcome.