Oxidation kinetics of cyclophosphamide and methotrexate by ozone in drinking water

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 O 3 = 3.3 ± 0.2 M −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 O 3 = 2.9 ± 0.3 M −1 s −1). The rate constant with hydroxyl radicals was higher at 2.0 × 10 9 M −1 s −1. Methotrexate reacted quickly with molecular ozone at dosages typically applied in drinking water treatment ( k O 3 > 3.6 × 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 × 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.