Physical and Chemical Stability of Dexamethasone Sodium Phosphate in Intravenous Admixtures Used to Prevent Chemotherapy-Induced Nausea and Vomiting.

Abstract

Purpose: Dilute intravenous (IV) admixtures of dexamethasone sodium phosphate (DSP) are becoming increasingly used in antiemetic regimens to prevent chemotherapy-induced nausea and vomiting (CINV). Based on its chemical structure and previous studies, DSP is known to be susceptible to hydrolysis and oxidation under certain conditions. There are limited data to directly support the selection of IV diluents, storage conditions, and beyond-use dates for the dilute IV solutions of DSP used in the antiemetic regimens. This study was designed to investigate these parameters. Methods: A stability-indicating high-performance liquid chromatography (HPLC) method was first developed for the analysis of DSP. Commercially available 100 mg/10 mL DSP injection vials were used to prepare the IV admixtures of DSP in 0.9% sodium chloride injection or 5% dextrose injection. The final DSP concentrations were 0.08 or 0.4 mg/mL, which bracketed the range commonly used in antiemetic regimens. These admixtures were packaged in 50-mL polyvinylchloride (PVC) bags and stored at room temperature or under refrigeration for 14 days. Samples from each IV bag underwent visual, pH, and HPLC assessments on days 0, 1, 3, 7, and 14. Results: Immediately after preparation, the IV admixtures of DSP appeared clear, colorless, and free of particulate matters. The initial pH values were 6.4 to 6.8 and 7.0 to 7.8 for samples in 0.9% sodium chloride and 5% dextrose, respectively. The initial DSP concentrations of all samples were within 96% to 100% of the expected values. Over the 14 days of storage at room temperature or refrigeration, no significant change was observed for the visual appearance of any IV bags. The pH of all samples remained within one pH unit from the initial values. The HPLC results confirmed that all samples retained 94% to 100% of original drug concentrations and that no significant degradation products were observed. Conclusions: Intravenous admixtures of DSP at 0.08 to 0.4 mg/mL are compatible with 0.9% sodium chloride and 5% dextrose in PVC bags. These admixtures are also chemically and physically stable when stored at room temperature or under refrigeration for up to 14 days.