Physico-Chemical Stability of Admixtures of Vinflunine Used in Clinical Practice

Abstract

Procedure of administration of vinflunine is complex and consists of an Y-site injection with fluid at different speeds. Dose is diluted with 100 mL of 0.9% sodium chloride or 5% glucose and infused with half of the 500 mL bag of the fluid over 20 min; after that, the remaining fluid is administered at 300 mL/h. In this study, chemical stability and physical compatibility of vinflunine diluted with in 500 mL of both fluids were evaluated to simplify the administration procedure (infusion of mixture on 20 min followed by 250 mL of fluid at 300 mL/h). Physical compatibility and chemical stability were evaluated at two temperatures and protected from and exposed to light. Physical compatibility was evaluated by visual inspection, gravimetric control and measure of pH. A chromatographic method was developed to evaluate chemical stability. The dilution of vinflunine with 500 mL of fluid to final concentrations of 0.75 and 1.54 mg/mL is viable at doses used in clinical practice since admixtures are stable for 2 days at room temperature and at least 7 days under refrigeration. These results extend the expiration date of mixtures of vinflunine administered by the usual procedure and confirm the viability of the proposed procedure since administration is simplified and stability of vinflunine is guaranteed.

Keywords: Administration; Chemical stability; Physical compatibility; Vinflunine.