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

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 x 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 (pK 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. (C) 2014 Elsevier B.V. All rights reserved.