title: Oxidation kinetics of cyclophosphamide and methotrexate by ozone in drinking water.
abstract: This study investigates the aqueous degradation by ozone of two target cytostatic drugs, cyclophosphamide and methotrexate. A column switching technique for on-line solid phase extraction (SPE) coupled to electro-spray ionization-tandem mass spectrometry (LC-ESI-MS/MS) was used for the simultaneous detection of the trace contaminants. The second-order kinetic rate constants for the reaction of cyclophosphamide with molecular ozone and hydroxyl radicals were determined in bench-scale experiments at pH 8.10. The molecular ozone oxidation kinetics was studied in buffered ultrapure water and compared to the oxidation kinetics in natural water from a municipal drinking water treatment plant in the province of Quebec (Canada). For cyclophosphamide, the degradation rate constant with molecular ozone in ultrapure water was low (k(O3)=3.3+/-0.2M(-1)s(-1)) and the extent of oxidation was linearly correlated to the ozone exposure. The impact of water quality matrix on oxidation efficacy was not significant during direct ozone reaction (k(O3) =2.9+/-0.3M(-1)s(-1)). The rate constant with hydroxyl radicals was higher at 2.0 x 10(9) M(-1)s(-1). Methotrexate reacted quickly with molecular ozone at dosages typically applied in drinking water treatment (k(O3)>3.6 x 10(3)M(-1)s(-1)). Overall, the results confirmed that organic compounds reactivity with ozone was dependent of their chemical structure. Ozone was very effective against methotrexate but high oxidant concentration x contact time (CT) values were required to completely remove cyclophosphamide from drinking water. Further studies should be conducted in order to identify the ozonation by-products and explore the impact of ozone on their degradation and toxicity.
authors.affiliation: Department of Chemistry, Université de Montréal, Succ. Centre-ville, Montréal, QC, Canada.
authors.forename: Araceli
authors.initials: A
authors.lastname: Garcia-Ac
authors.forename: Romain
authors.initials: R
authors.lastname: Broséus
authors.forename: Simon
authors.initials: S
authors.lastname: Vincent
authors.forename: Benoit
authors.initials: B
authors.lastname: Barbeau
authors.forename: Michèle
authors.initials: M
authors.lastname: Prévost
authors.forename: Sébastien
authors.initials: S
authors.lastname: Sauvé
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000032:analysis / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D003520:Cyclophosphamide / Q000032:analysis / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008727:Methotrexate / Q000032:analysis / Q000737:chemistry*; D010084:Oxidation-Reduction; D010126:Ozone / Q000737:chemistry*; D052616:Solid Phase Extraction; D021241:Spectrometry, Mass, Electrospray Ionization; D014874:Water Pollutants, Chemical / Q000032:analysis / Q000737:chemistry*; D018508:Water Purification; D014881:Water Supply
chemical_list: D000964:Antimetabolites, Antineoplastic; D014874:Water Pollutants, Chemical; D010126:Ozone; D003520:Cyclophosphamide; D008727:Methotrexate