Fiche publication
Date publication
décembre 1995
Journal
Bulletin du cancer
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BARBERI-HEYOB Muriel
,
Pr MERLIN Jean-Louis
Tous les auteurs :
Barberi-Heyob M, Watelet M, Merlin JL, Bleger C, Schroeder B
Lien Pubmed
Résumé
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.
Mots clés
Antimetabolites, Antineoplastic, analysis, Buffers, Chromatography, High Pressure Liquid, Drug Delivery Systems, Drug Packaging, Drug Stability, Drug Storage, Fluorouracil, analysis, Lighting, Solutions, Temperature, Time Factors
Référence
Bull Cancer. 1995 Dec;82(12):1025-31
