Stability of commercial solutions of 5-fluorouracil for continuous infusion in an ambulatory pump.
OBJECTIVE
The stability of 5-fluorouracil (FU) Roche solutions in a portable infusion pump under prolonged "in-use" conditions (32 degrees C, 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 19F NMR immediately after preparation (T0) and after 2, 3 or 10 days (TF) 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 T0 and TF, 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 2 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 2 days at 25 degrees C, low levels of FMASAld were present but Facet could still not be detected.


CONCLUSIONS
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.
Fournet
A
A
Biomedical NMR Group, UMR CNRS 5623, Université Paul Sabatier, 118, route de Narbonne, 31062 Toulouse, France.
Gilard
V
V
Malet-Martino
M
M
Martino
R
R
Canal
P
P
De Forni
M
M
D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000737:chemistry*; D004355:Drug Stability; D005462:Fluorine Radioisotopes; D005472:Fluorouracil / Q000008:administration & dosage / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007260:Infusion Pumps; D009682:Magnetic Resonance Spectroscopy; D013997:Time Factors
D000964:Antimetabolites, Antineoplastic; D005462:Fluorine Radioisotopes; D005472:Fluorouracil