title: 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 (kapp) of 5FU removal by chlorine and bromine were strongly pH dependent and had maximum 14.8M(-1)s(-1) and 1.9×10(3)M(-1)s(-1)kapp values, respectively at pH 7. Modeling of the dependence of the kapp 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.
authors: College of Forest Resources and Environment, Nanjing Forestry University, Longpan Road 159, Nanjing 210037, China; Key Laboratory of Pollution Processes and Environmental Criteria (Nankai University), Ministry of Education, Tianjin 300071, China. Electronic address: uwliwei@gmail.com.
authors: Wei
authors: W
authors: Li
authors: Department of Civil and Environmental Engineering, University of Washington, Box 352700, Seattle, WA 98195-2700, United States.
authors: Jessica
authors: J
authors: Tanumihardja
authors: Water Environment Laboratory, Department of Civil and Environmental Engineering, Tokyo Institute of Technology, Ookayama 2-12-1-M1-4, Tokyo 152-8552, Japan.
authors: Takaaki
authors: T
authors: Masuyama
authors: Department of Civil and Environmental Engineering, University of Washington, Box 352700, Seattle, WA 98195-2700, United States.
authors: Gregory
authors: G
authors: Korshin
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry*; D001966:Bromine / Q000737:chemistry*; D002713:Chlorine / Q000737:chemistry*; D005472:Fluorouracil / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D014865:Waste Disposal, Fluid; D014874:Water Pollutants, Chemical / Q000737:chemistry*; D018508:Water Purification
chemical_list: D000970:Antineoplastic Agents; D014874:Water Pollutants, Chemical; D002713:Chlorine; D001966:Bromine; D005472:Fluorouracil
keywords: 5-Fluorouracil; Bromination; Chlorination; Degradation pathway; Kinetics