Physical and chemical stability of etoposide phosphate solutions.

Abstract

To evaluate the physical and chemical stability of etoposide phosphate solutions over 7 days at 32 degrees C and 31 days at 4 degrees C and 23 degrees C: (1) at etoposide concentrations of 0.1 and 10 mg/mL as phosphate in 0.9% sodium chloride injection and 5% dextrose injection and (2) at etoposide concentrations of 10 and 20 mg/mL as phosphate in bacteriostatic water for injection packaged in plastic syringes. Test samples of etoposide phosphate were prepared in polyvinyl chloride (PVC) bags of the two infusion solutions at etoposide concentrations of 0.1 and 10 mg/mL as phosphate. Additional test samples were prepared in bacteriostatic water for injection containing benzyl alcohol 0.9% at etoposide concentrations of 10 and 20 mg/mL as phosphate and were packaged in 5 mL plastic syringes. Evaluations for physical and chemical stability were performed initially; after 1 and 7 days of storage at 32 degrees C; and after 1, 7, 14, and 31 days of storage at 4 degrees C and 23 degrees C. Physical stability was assessed using visual observation in normal light and using a high-intensity monodirectional light beam. Turbidity and particle content were measured electronically. Chemical stability of the drug was evaluated by using a stability-indicating high-performance liquid chromatographic (HPLC) analytic technique. All samples were physically stable throughout the study. Little or no change in particulate burden and haze level were found. In the intravenous infusion solutions, little or no loss of etoposide phosphate occurred in any of the samples throughout the study period. The 10 and 20 mg/mL samples in bacteriostatic water for injection repackaged in syringes were also stable throughout the study, exhibiting a maximum of 6% or 7% loss after 31 days of storage at 23 degrees C and less than 4% in 31 days at 4 degrees C. Etoposide phosphate prepared as intravenous admixtures of etoposide 0.1 and 10 mg/mL as phosphate in 5% dextrose injection and 0.9% sodium chloride injection in PVC bags and as etoposide 10 and 20 mg/mL as phosphate in bacteriostatic water for injection packaged in plastic syringes is physically and chemically stable for at least 7 days at 32 degrees C and 31 days at 4 degrees C and 23 degrees C. This new water-soluble phosphate-ester of etoposide formulation solves the precipitation problems associated with the old organic solvent and surfactant-based formulation.