Physicochemical stability of Oxaliplatin beta infusion concentrate and infusion solutions in polyethylene bags prefilled with 5% glucose vehicle solution over a 28 day period

Background

Oxaliplatin beta is marketed in Germany by Betapharm as an infusion concentrate (5 mg/mL) which should be diluted with 5% w/v glucose infusion solution (G5) as vehicle to achieve oxaliplatin concentrations in the range of 0.2 mg/mL and 1 mg/mL.

Aim

The aim was to evaluate the physico-chemical stability of Oxaliplatin beta infusion concentrate in original vials andof diluted infusions solutions (0.2 mg/mL, 1 mg/mL) in G5 vehicle solution in polyethylene PE bags stored under light protection, either refrigerated or at room temperature over a period of 28 days.

Method

The chemical stability of Oxaliplatin infusion concentrate and diluted infusion solutions was determined by using a validated HPLC assay with UVdetection. Oxaliplatin infusion concentrate (5 mg/mL) was stored in the original vials which were re-punctured over the test period of 28 days. The diluted infusion solutions were prepared in prefilled 5% glucose PE infusion bags to achieve a concentration of 0.2 mg/mL or 1 mg/mL oxaliplatin. Three test solutions each were stored light protected, either refrigerated (2-8 °C) or at room temperature (22 °C). Samples were taken at predetermined intervals and measured in triplicate over a 28 day storage period. Physical stability was by determined by measurement of the pH value, visible and sub-visible particles.

Results

Oxaliplatin infusion concentrate in original vials and diluted infusion solutions in PE infusion bags remained physically and chemically stable over a 28 day storage period while stored light protected, either refrigerated or at room temperature. Visible particles were not detected. Subvisible particles corresponds the request of Ph. Eur. 7.1 and the USP

Conclusion

Oxaliplatin beta infusion concentrate can be re-used over a period of 28 days. Diluted infusion solutions in G5 vehicle solutions in PE bags are physico-chemically stable over a 28 day storage period storage either refrigerated or at room temperature, thereby facilitating preparation in advance and dose-banding.