ABSTRACT
Kinetics of photodegradation of novel oral anticoagulants dabigatran, rivaroxaban, and apixaban were studied under simulated solar light irradiation in purified, mineral, and river waters. Dabigatran and rivaroxaban underwent direct photolysis with polychromatic quantum yields of 2.2 × 10-4 and 4.4 × 10-2, respectively. The direct photodegradation of apixaban was not observed after 19 h of irradiation. Kinetics of degradation of rivaroxaban was not impacted by the nature of the aqueous matrix while photosensitization from nitrate ions was observed for dabigatran and apixaban dissolved in a mineral water. The photosensitized reactions were limited in the tested river water (Isle River, Périgueux, France) certainly due to the hydroxyl radical scavenging effect of the dissolved organic matter. The study of photoproduct structures allowed to identify two compounds for dabigatran. One of them is the 4-aminobenzamidine while the second one is a cyclization product. In the case of rivaroxaban, as studied by very high field NMR, only one photoproduct was observed i.e. a photoisomer. Finally, seven photoproducts were clearly identified from the degradation of apixaban under simulated solar light.
Subject(s)
Anticoagulants/radiation effects , Fresh Water/chemistry , Photolysis/radiation effects , Sunlight , Benzamidines , France , Hydroxyl Radical , Kinetics , Pyrazoles , Pyridones , Water Pollutants, Chemical/analysis , Water Pollutants, Chemical/radiation effectsABSTRACT
This study was conducted to gain a better understanding of the fate of fluoroquinolone antibacterial ofloxacin (OFX) which is the free available chlorine (FAC) in order to determine its effect during water chlorination process. The Direct reactions of FAC with OFX were quite rapid. A half-life of 7.7 s was measured under pseudo-first order conditions in the presence of an excess of total chlorine ([FAC]0 = 13 µM and [OFX]0 = 0.55 µM at pH 7.2 and 20 °C in buffered reagent water. Free chlorine reactions rates were of first-order type in both substrate and oxidant with specific second-order rate constants of 6.8 × 103 M-1 s-1. No induced back reactions or other interference by using thiosulfate to stop the chlorination reaction was shown. The seven products of the reaction were determined by using the LC/MS/MS analysis. Structures were investigated due to the explication of transitions obtained at different CID energies by LC-ESI-MS/MS. Pathways of the formations of these by-products were presented in this study and pathways of the fragmentations of pseudo molecular ions of the structures proposed were presented in supplementary files.
Subject(s)
Chlorine/chemistry , Ofloxacin/chemistry , Anti-Bacterial Agents/chemistry , Chromatography, Liquid , Disinfection , Half-Life , Halogenation , Hydrogen-Ion Concentration , Kinetics , Tandem Mass Spectrometry , Water Pollutants, Chemical/chemistry , Water Purification/methodsABSTRACT
In this study, we aimed to investigate the kinetics and the mechanism of reaction of the fluoroquinolone antibacterial danofloxacin (DANO) by free available chlorine (FAC) during water chlorination process. Kinetic study was thus performed at pH 7.2, 20 °C in the presence of an excess of total chlorine. Under these experimental conditions, a second-order reaction rate constant (first-order relative to DANO concentration and first-order relative to FAC concentration) was evaluated to k~1446 M-1 s-1. Five degradation products were identified at different reaction times. Their structures were investigated by using fragmentations obtained at different CID collision energies in MS/MS experiments. Moreover, the toxicity of the proposed structures was predicted by using T.E.S.T. PROGRAM: The results indicated that all by-products may have a developmental toxicity. The oral rat LD50 concentration was predicted to be lower than that of DANO. Furthermore, two degradation compounds presented a concentration level for fathead minnow LC50 (96 h) lower than that of DANO and presented toxicity for the marine animals.