Stability of commercial solutions of 5-fluorouracil for continuous infusion in an ambulatory pump

Purpose: The stability of 5-fluorouracil (FU) Roche solutions in a portable infusion pump under prolonged "in-use" conditions (32 degreesC, in the dark) was studied, especially with respect to the formation of the cardiotoxic compounds fluoroacetaldehyde (Facet) and fluoromalonic acid semialdehyde (FMASAld). Methods: The solutions, prepared according to three protocols frequently used at the Anticancer Centre in Toulouse, were analysed by F-19 NMR immediately after preparation (T-0) and after 2, 3 or 10 days (T-F) in the pump. Results: The commercial solution already contained 64 fluorinated "impurities", among them fluoride ion (F-), FMASAld and Facet. The concentration of FU did not change significantly between T-0 and T-F, whatever the protocol. The levels of F- had not increased significantly after 2 or 3 days, but had increased by about 50% after 10 days. The increases in FMASAld levels were low (12 -28%) albeit significant in the three protocols. The levels of Facet had increased by a factor of about 2 after 2 or 3 days, and by a factor of > 3 after 10 days. The levels of the other fluorinated compounds were constant during the first 3 Or 3 days, but had increased by about 30% after 10 days. FU Dakota lyophilizates. analysed immediately after reconstitution, contained neither FMASAld nor Facet. After 3 dugs at 25 degreesC, low levels of FMASAld were present but Facet could still not be detected. Conclusion: This study showed that special attention must be paid to the risk of increasing concentrations of highly toxic FMASAld and Facet when FU is administered via a pump for long periods of time. It would be preferable not to exceed 3 days of treatment when patients receive FU from a portable infusion pump. This underlines the interest in using a lyophilized formulation of FU in clinical practice.