Effects of PVC bags sterilization process on the 5-fluorouracil stability

The stability and compatibility of 5-fluorouracil (5-FU) in undiluted or diluted admixtures stored in beta-radiation sterilized portable poly(vinyl chloride) (PVC) infusion bags were investigated. Admixtures containing 5-FU 50 mgml(-1) not diluted or 25 mgml(-1) diluted in 0.9% sodium chloride injection were placed in 100 or 250 mi empty PVC reservoirs sterilized initially by beta-irradiation. They were protected from light and placed at 37 degrees C. Two mi quantities were withdrawn immediately after preparation and after storage for 1, 2, 3, 4, 5, 6, 7 and 14 days. For each condition, samples from each admixture were tested for drug concentration by stability-indicating high-performance liquid chromatography. The admixtures were also monitored for precipitation, color change and pH. Evaporative water loss from the containers was also measured. 5-FU was compatible with PVC containers in all tested conditions for 14 days. No loss of drug and no color change were detected throughout the storage period. pH values were stable and neither precipitation nor loss of water through the reservoirs was observed when drug 50 or 25 mgml(-1) (diluted using 0.9% sodium chloride) was stored in 100 mi capacity polyvinyl PVC bags. However, when stored in 250 mi capacity PVC bags, the 5-FU solution showed precipitation after 13 and 14 days of storage, but no drug loss was detected due to a substantial loss of water. The precipitation of the drug was due to the decrease of pH induced by the dehydrochlorination of PVC during P-irradiation leading to the formation of hydrochloric acid in solution. Differences observed between 100 and 250 mi capacity bags can be explained by the greater area of PVC present in 250 mi reservoirs, and consequently more HCl formed. Finally, more plasticizer, di-(2-ethylhexyl) phthalate (DEHP), was then detected in drug solutions stored in 250 mi PVC bags. So, we recommend the use of 100 mi bags to store 5-FU at longer storage times and higher temperatures. (C) 1999 Elsevier Science Ltd. All rights reserved.