Physicochemical stability of irinotecan injection concentrate and diluted infusion solutions in PVC bags

Abstract

Purpose. To determine the physicochemical stability of irinotecan injection concentrate and irinotecan infusion solutions after dilution in two commonly used infusion fluids (0.9% sodium chloride, 5% dextrose) in PVC bags, stored under refrigeration (2-8°C) or at room temperature either light protected or exposed to light.

Methods. Stability of irinotecan injection concentrate was determined in the original amber glass vials. Diluted irinotecan infusion solutions were aseptically prepared by further dilution of irinotecan stock solution with either 0.9% sodium chloride or 5% dextrose in PVC bags, in amounts yielding irinotecan concentrations of 0.4, 1.0, or 2.8 mg/ml. Test solutions were stored under refrigeration (2-8°C) or at room temperature either light protected or exposed to light (mixed daylight and normal laboratory fluorescent light) in parallel. Irinotecan concentrations were determined periodically throughout a 4-week storage period via a stability-indicating HPLC assay with ultraviolet detection. In addition, measurements of pH values were performed regularly and test solutions were visually examined for colour change and precipitation.

Results. Irinotecan injection concentrate and infusion solutions are shown to be physicochemically stable (at a level of >90% irinotecan) for 4 weeks when stored under refrigeration or light protected at room temperature, independent of the vehicle (0.9% sodium chloride, 5% dextrose) or the concentration (0.4, 1.0, or 2.8 mg/ml). Irinotecan infusion solutions exposed to daylight exhibited concentration-dependent instability, solutions were stable for only 7 to 14 days.

Conclusions. Irinotecan injection concentrate and diluted infusion solutions are shown to have adequate physicochemical stability for convenient pharmacy-based centralized preparation.