Fast and complete removal of the 5-fluorouracil drug from water by electro-Fenton oxidation
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Cytostatic drugs are a troublesome class of emerging pollutants in water owing to their potential effects on DNA. Here we studied the removal of 5-fluorouracil from water using the electro-Fenton process. Galvanostatic electrolyses were performed with an undivided laboratory-scale cell equipped with a boron-doped diamond anode and a carbon felt cathode. Results show that the fastest degradation and almost complete mineralization was obtained at a Fe2+ catalyst concentration of 0.2 mM. The absolute rate constant for oxidation of 5-fluorouracil by hydroxyl radicals was 1.52 × 109 M−1 s−1. Oxalic and acetic acids were initially formed as main short-chain aliphatic by-products, then were completely degraded. After 6 h the final solution mainly contained inorganic ions (NH4 +, NO3 − and F−) and less than 10% of residual organic carbon. Hence, electro-Fenton constitutes an interesting alternative to degrade biorefractory drugs.
Keywords5-Fluorouracil Antineoplastic BDD Cytostatic Electro-Fenton Water decontamination
Pharmaceuticals are non-regulated trace organic emerging contaminants that are ubiquitous in the aquatic environment due to discharge of effluents from pharmaceutical industry, hospitals and municipal wastewater treatment facilities (Feng et al. 2015; Petrie et al. 2015). In most cases, these pollutants are also present in the digested sludge, potentially entailing a high ecotoxicological risk (Martín et al. 2012). In order to avoid the propagation and subsequent accumulation of pharmaceutically active compounds in water bodies, specific prevention systems should be devised at major point sources of pollution. In the case of pharmaceuticals, such locations are hospitals and production sites. Unfortunately, removal efficacy data are scarce since the vast majority of the studies only focus on their impact on pharmaceutical loads.
The most hazardous representatives among these pollutants are those with a very powerful pharmacological action. Among them, the class of cytostatic (antineoplastic) drugs, used to prevent or inhibit the growth of malignant cells or tumors, can display severe negative effects on nontarget organisms including humans, like carcinogenicity, cytotoxicity, genotoxicity, mutagenicity and teratogenicity (Kosjek et al. 2013). 5-Fluorouracil (Fig. 1) belongs to the subclass of antimetabolites, and its consumption reaches the range of tonnes in Europe. Several studies have reported its presence in natural water at concentrations ranging from ng L−1 to μg L−1 (Lutterbeck et al. 2016).
The fundamentals and reactivity of electro-Fenton process are well described elsewhere (Brillas et al. 2009). Electro-Fenton has been successfully employed for the treatment of acidic aqueous solutions containing antibiotics, antidepressants or β-blockers, among others, using undivided electrolytic cells with different anodes (Sirés et al. 2010; Dirany et al. 2012; Estrada et al. 2012; Panizza et al. 2014; Salazar et al. 2017). However, there have been no studies dealing with the application of electro-Fenton to the degradation of cytostatic agents. Regarding 5-fluorouracil, only a few publications have reported its treatment by AOP, including photocatalysis with TiO2 (Lin and Lin 2014), UV/H2O2 (Lutterbeck et al. 2015), as well as Fenton and photo-Fenton processes (Governo et al. 2017; Koltsakidou et al. 2017). In this context, the aim of the present work is to optimize the key operation parameters for a fast drug decay and large mineralization of aqueous solutions of the emerging pollutant 5-fluorouracil by electro-Fenton using a BDD/carbon felt cell, trying to confirm the great oxidation power of this method to treat highly biorecalcitrant molecules.
The cytostatic drug 5-fluorouracil was of analytical grade (purity higher than 99%) from Sigma-Aldrich, and it was used as received. Solutions were prepared with ultra-pure water obtained from a Millipore Simplicity 185 water purification system with resistivity higher than 18 MΩ cm. Iron(II) sulfate heptahydrate used as source of Fe2+ ions (catalyst) and sodium sulfate added as supporting electrolyte were of analytical grade from Acros Organics and Sigma-Aldrich, respectively. Sulfuric acid from Merck was added to adjust initial pH of all solutions. Salts used as standard in ion chromatography were of ACS grade (purity higher than 99.5%) from Sigma-Aldrich. Methanol used as organic solvent for high-performance liquid chromatography (HPLC) was purchased from VWR.
A bench-scale, open, undivided glass cell was used in batch operation mode at room temperature to carry out galvanostatic electrolyses using an HM8040-3 Hameg power supply. The cell was filled with 200 mL of a 0.1 mM drug solution containing 0.05 M Na2SO4 and a given amount of FeSO4, at pH 3.0 since it is the optimal value for performing electro-Fenton treatments (Brillas et al. 2009). A carbon felt cathode (18.5 cm × 4.5 cm) from Carbone-Lorraine was placed covering the inner wall of the cell, and a PTFE mesh was used to keep it apart from the anode, a thin film BDD on niobium substrate (6.0 cm × 4.0 cm) centered in the cell. The solution was saturated with O2 by sparging compressed air at 1 L min−1, starting 15 min before electrolysis, and continuous stirring (450 rpm) was maintained during the trials. The experiments were run in triplicate.
Drug decays were monitored by reversed-phase HPLC using a Merck Lachrom chromatograph fitted with a Purospher Star RP-18, 5 µm, 25 cm × 4.6 mm (i.d.), column at 40 °C and coupled with an Elite Lachrom L-2400 UV detector selected at λ = 277 nm. Analyses were carried out isocratically by using a 5:95 (v/v) methanol/water mixture, both with 0.1% acetic acid, at 0.4 mL min−1, employing the EZChrom Elite 3.1 software. In competition kinetics experiments (see Panizza et al. 2014), the HPLC analysis was made with a 30:70 (v/v) methanol/water solution (0.1% acetic acid in each) as mobile phase at 0.3 mL min−1. Short-chain carboxylic acids were determined by ion-exclusion chromatography using the same equipment, with a Supelcogel H, 9 µm, [25 cm × 4.6 mm (i.d.)] column at room temperature, the detector set at λ = 210 nm and using 1% H2SO4 as mobile phase at 0.2 mL min−1. Inorganic ions were analyzed on a Dionex ICS-1000 chromatograph that included self-regenerating suppressors. The system was equipped with a DS6 conductivity detector containing a cell heated at 35 °C. An anion-exchange column (IonPac AS4ASC, 25 cm × 4 mm) fitted with an IonPac AG4A-SC column guard was used to analyze the anions. For cations (NH4 +), a cation-exchange column (IonPac CS12A, 25 cm × 4 mm) fitted with an IonPac CG12A column guard was used. A mixture of 1.8 mM Na2CO3 and 1.7 mM NaHCO3 at 2.0 mL min−1 and a 9.0 mM H2SO4 solution at 1.0 mL min−1 were eluted as mobile phases. The mineralization of each solution was monitored from the total organic carbon (TOC) abatement, using the non-purgeable organic carbon method with ± 2% accuracy, determined on a Shimadzu VCSH analyzer. The average values with an error below 2% are reported in all figures.
Results and discussion
Optimization of electro-Fenton parameters for 5-fluorouracil removal
Mineralization of 5-fluorouracil solutions and by-products generated
The fastest destruction of cytotoxic drug 5-fluorouracil by electro-Fenton process (6 min at 300 mA) was reached at an optimum Fe2+ concentration of 0.2 mM. Regarding the mineralization of 5-fluorouracil solutions, the application of 1500 mA ensured the abatement of more than 94% TOC. The second-order rate constant (k abs) for oxidizing this drug with hydroxyl radical was determined for the first time. Electro-Fenton process is shown as highly effective for destroying cytostatic pharmaceutical residues in water.
O. Ganzenko thanks financial support from European Commission (EPA No. 2010-0009) through the Erasmus Mundus Joint Doctorate Programme (ETeCoS3).
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