Examination of the kinetics of degradation of the antineoplastic drug 5-fluorouracil by chlorine and bromine

Abstract This study examined the degradation of the widely used antineoplastic drug 5-fluorouracil (5FU) by chlorine and bromine. 5FU was determined to interact readily with free chlorine and bromine but was stable in the presence of chloramine. The removal of 5FU followed a second-order kinetic pattern. Apparent rates ( k app ) of 5FU removal by chlorine and bromine were strongly pH dependent and had maximum 14.8 M −1  s −1 and 1.9 × 10 3  M −1  s −1 k app values, respectively at pH 7. Modeling of the dependence of the k app values vs. pH indicated the presence of a relatively acidic (p K 6.4 vs. 8.5 of 5FU per se) 5FU intermediate generated in the presence of halogen species. Spectrophotometric measurements confirmed the increased acidity of 5FU chlorination products and allowed proposing a degradation pathway of 5FU by chlorine. This pathway suggests that 5FU chlorination proceeds via chlorine incorporation at the 6th carbon in the heterocyclic ring of 5FU.