[Stability of 5-fluorouracil solutions according to different parameters]

To follow therapeutic evolutions and to ensure an international homogeneity, "Produits Roche" Laboratories recently modified the conditioning of 5-fluorouracil (5-FU): the Tris buffer was replaced by sodium hydroxide (pH 9.4). For these newly-formulated 5-FU solutions, we studied the optimal conditions of storage according to concentration (0.2; 1.5 and 10 mg/ml), temperature (4, 21 and 37 degrees C), light (without, natural, artificial) and duration (7, 15 and 30 days) for plastic bags, syringes and cassettes. 5-FU was dosaged by High Performance Liquid Chromatography (HPLC). No staining was observed, but for the samples placed at 4 degrees C, we detected macroscopically the apparition of crystals, more or less rapidly according to 5-FU concentration. For plastic bags at 0.2 mg/ml of 5-FU in NaCl (0.9%), 48 hours were sufficient for crystallisation. For preparations at 10 and 50 mg/ml, the formation of crystals occurred in less than 24 hours. However, no microscopic analysis was performed and therefore, in shorter delays, the formation of microcrystals can be envisaged. After 7 days, only the storage in darkness at 21 degrees C yields good results of stability for cassettes and syringes at 50 mg/ml with a degradation of the active component that does not exceed 2%. However, in the same optimal conditions, a storage superior to 14 days cannot be envisaged since we noted a 10% diminution of the active component, then this loss intensifies and reaches 18% after 30 days of storage. For plastic bags at 0.2 and 1.5 mg/ml of 5-FU, we did not measure any significant difference between the various storage conditions, even during 14 days. At 10 mg/ml concentration, a storage during 7 days in darkness can be envisaged with no repercussion on the 5-FU stability. Independently of concentration, special attention must be paid to the risk of crystallisation at 4 degrees C.