Stability of topotecan infusion solutions in polyvinylchloride bags and elastomeric portable infusion devices

Abstract

Purpose. The purpose of this study was to determine the physicochemical stability of topotecan after reconstitution and after further dilution in two commonly used infusion fluids (0.9% sodium chloride, 5% dextrose) in both polyvinylchloride (PVC) bags and elastomeric portable infusion devices.

Methods. Each vial of topotecan (Hycamtin®) was reconstituted with sterile water for injection, yielding a nominal concentration of 1 mg/mL. Topotecan infusion solutions were aseptically prepared by further dilution of reconstituted topotecan solutions with either 0.9% sodium chloride or 5% dextrose in both PVC bags and portable elastomeric infusion devices, in amounts yielding topotecan concentrations of 10 µg/mL, 25 µg/mL, or 50 µg/mL. Test solutions were stored light-protected at room temperature (25°C) or under refrigeration (2-8°C) in parallel. One test solution of the nominal concentration of 10 µg/mL topotecan in a 0.9% sodium chloride PVC infusion bag was stored under ambient light conditions (mixed daylight and normal laboratory fluorescent light) at room temperature. Topotecan concentrations were obtained periodically throughout a 4-week storage period via a stability-indicating high performance liquid chromatography assay with ultra-violet detection. In addition, measurements of pH values were performed regularly, and test solutions were visually examined for colour change and precipitation.

Results. The stability tests revealed that the currently available topotecan formulation is stable (at a level of ≥90% topotecan) after reconstitution and dilution, independent of temperature (refrigerated, room temperature), the vehicle (0.9% sodium chlo-ride, 5% dextrose), the concentration (10 µg/mL, 25 µg/mL, or 50 µg/mL), or the container material (PVC bags, elastomeric portable infusion devices). The results were obtained over a test period of ≥4 weeks. Topotecan infusion solutions exposed to daylight were stable for only 17 days.

Conclusions. Reconstituted and diluted topotecan infusion solutions are shown to be physicochemically stable for 4 weeks. Light protection during administration is not necessary.