Environmental Chemistry Letters

, Volume 16, Issue 1, pp 281–286 | Cite as

Fast and complete removal of the 5-fluorouracil drug from water by electro-Fenton oxidation

  • Oleksandra Ganzenko
  • Nihal Oturan
  • Ignasi Sirés
  • David Huguenot
  • Eric D. van Hullebusch
  • Giovanni Esposito
  • Mehmet A. Oturan
Original Paper


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.


5-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).

Conventional water treatment methods based on biological processes have been shown as insufficient to eliminate the majority of target pharmaceuticals because of their high recalcitrance and toxicity to bacteria (Kovalova et al. 2012). 5-Fluorouracil is not an exception, and, furthermore, it has been demonstrated that photodegradation by sun is not suitable for its removal either, showing partial degradation and no mineralization (Lutterbeck et al. 2016). Therefore, it does not undergo natural attenuation in the environment and cannot be removed in traditional treatment plants. Chemical degradation with NaClO or H2O2 could be an option to face up to this troubling situation, as tested in the hospital environment (Castegnaro et al. 1997). Alternatively, several enhanced water treatment technologies have been developed in recent years. In particular, the advanced oxidation processes (AOP), which utilize strong reactive oxidant species like hydroxyl radicals (\({^{ \bullet } {\text{OH}}}\)) generated on site, present appealing perspectives for treating biorefractory pollutants (Oturan and Aaron 2014). A relatively new group of AOP is constituted by electrochemical methods such as electro-oxidation, Fenton-based electrochemical AOP and photoelectrocatalysis, whose great performance during the treatment of pharmaceuticals has been thoroughly reviewed (Sirés and Brillas 2012; Feng et al. 2013; Brillas and Sirés 2015). The common feature of all the EAOPs is their ability to generate reactive oxygen species (ROS), as either superoxides (MOx) or hydroxyl radicals (M(\({^{ \bullet } {\text{OH}}}\))), adsorbed on the anode (M) surface from the oxidation of water. Active anodes like Pt promote the formation of the first kind of ROS, whereas non-active anodes like boron-doped diamond (BDD) foster the second type via reaction (1). However, only the Fenton-based electrochemical AOP like electro-Fenton process are able to produce homogeneous \({^{ \bullet } {\text{OH}}}\) from Fenton’s reaction (2) thanks to the in situ generation of H2O2 from the two-electron cathodic reduction of O2:
$${\text{M }} + {\text{ H}}_{ 2} {\text{O}} \to {\text{M}}(^{ \bullet } {\text{OH}}) + {\text{H}}^{ + } + {\text{e}}^{ - }$$
$${\text{Fe}}^{2}+ {\text{ H}}_{ 2} {\text{O}}_{ 2} \to {\text{Fe}}^{{ 3 { + }}} + ^{{\bullet}}\!{{\text{OH}} }+ {\text{OH}}^{ - }$$

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

The catalyst content and applied current (I) are the most crucial operation parameters to be optimized in electro-Fenton treatments. First, the effect of the initial Fe2+ concentration on 5-fluorouracil destruction was studied at 300 mA. The drug decay with electrolysis time is represented in Fig. 1 as the ratio between the concentrations of pollutant at time t and before the electrolysis. As can be observed, the destruction of the drug was quick and complete in all cases. At 0.1 mM Fe2+, total disappearance is attained in only 7 min, thanks to the synergistic action of \({^{ \bullet } {\text{OH}}}\) formed in the bulk and BDD (\({^{ \bullet } {\text{OH}}}\)) adsorbed on the anode surface (Brillas et al. 2009). The oxidation is accelerated when increasing the initial Fe2+ content to 0.2 mM, achieving a significantly quicker decay at the early stages and an overall removal at 6 min. This enhancement can be explained by the larger production of \({^{ \bullet } {\text{OH}}}\) from Fenton’s reaction (2), since the carbon felt cathode electrogenerates enough H2O2 so as to react with the higher amount of catalyst and, furthermore, it is able to continuously regenerate Fe2+ from Fe3+ reduction. Conversely, the degradation rate decreases upon further increase of the Fe2+ content to 0.5 mM, needing again 7 min for complete disappearance. This behavior was confirmed by the corresponding apparent rate constant (k app) values for the analysis of decay trends assuming a pseudo-first-order reaction kinetics (R 2 above 0.985 in all cases). Values of 0.57, 0.74 and 0.54 min−1 were obtained as the Fe2+ concentration was increased from 0.1 to 0.5 mM. The existence of a maximum arises from the fact that an excessive amount of catalyst triggers a number of parasitic reactions that cause quenching of \({^{ \bullet } {\text{OH}}}\) and BDD(\({^{ \bullet } {\text{OH}}}\)), especially their consumption by Fe2+ to form a less reactive catalyst (Fe3+).
Fig. 1

Effect of Fe2+ concentration on the degradation of 0.1 mM 5-fluorouracil with electrolysis time during the electro-Fenton treatment at 300 mA. Results show that 0.2 mM Fe2+ is the optimal catalyst concentration for degrading 5-fluorouracil by the electro-Fenton process

Afterward, the effect of the applied current for treating acidic 0.1 mM 5-fluorouracil solutions was studied using 0.2 mM Fe2+. The time-course of normalized drug concentration is shown in Fig. 2. Again, a fast and total destruction is achieved, being required a shorter time as current increases. For example, the application of currents from 50 to 300 mA allows shortening the required time from 9 to 6 min. This is due to the gradually greater production of BDD(\({^{ \bullet } {\text{OH}}}\)) from reaction (1), as well as of \({^{ \bullet } {\text{OH}}}\) via reaction (2) due to the upgrading of H2O2 cathodic electrogeneration. In contrast, the application of a higher current like 400 mA is detrimental, since the process becomes slower so as to need 7 min to completely remove the drug. This can also be confirmed from the right panel of Fig. 2, which informs about the dependence of the percentage of drug removal at 2 min on the applied current. The values of k app ranged between 0.38 and 0.60 min−1, with a maximum of 0.74 min−1 appearing at 300 mA. As mentioned above, this deceleration can be justified by the larger extent of parasitic reactions, such as the attack of hydroxyl radicals onto the extra H2O2 as well as onto the reaction intermediates (whose formation rate increases as current rises), along with the promotion of the four-electron reduction of O2 to H2O. Analogous dependence of k app on current was found for electro-Fenton treatments with 0.1 and 0.5 mM Fe2+, although in those cases the k app-range was remarkably lower, from 0.26 to 0.42 and 0.16 to 0.40 min−1, respectively, confirming the superiority of 0.2 mM Fe2+. From competition kinetics trials using p-hydroxybenzoic acid as reference (Oturan and Aaron 2014), the absolute rate constant (k abs) for the reaction between 5-fluorouracil and hydroxyl radical was determined for the first time, obtaining (1.52 ± 0.01) × 109 M−1 s−1.
Fig. 2

Effect of applied current on the degradation of 0.1 mM 5-fluorouracil during the electro-Fenton treatment with 0.2 mM Fe2+. Drug concentration decay is accelerated with increasing current, being the treatment optimal at 300 mA (left). The graph on the right shows the percentage of drug removal attained at 2 min versus the applied current, reaching a 79.3% at 300 mA

Mineralization of 5-fluorouracil solutions and by-products generated

The effect of Fe2+ content and current on the mineralization ability of the electro-Fenton process is shown in Fig. 3 as the percentage of TOC removal with time. Figure 3A confirms that 0.2 mM Fe2+ is also the optimal concentration for the degradation of reaction intermediates, since the removal percentage increased from 76 to 86% at 360 min. Further increase of the catalyst content to 0.5 mM was detrimental, with a slower and lower final mineralization of 82%. In order to assess the possibility of attaining larger TOC removals, current was tested from 200 to 1500 mA (Fig. 3B). As can be seen, almost overall mineralization (higher than 94%) was achieved at the highest current value due to the simultaneous action of hydroxyl radicals onto the parent drug and its intermediates, whereas gradually lower percentages were achieved as the applied current decreased. Depending on the energy cost, currents lower than 1500 mA can be chosen, still attaining more than 90% mineralization at long time.
Fig. 3

Percentage of total organic carbon (TOC) abated versus electrolysis time during the electro-Fenton treatment of 0.1 mM 5-fluorouracil solutions. A Effect of Fe2+ content as in Fig. 1. B Effect of applied current as in Fig. 2, but within a higher range. Mineralization is optimal at 0.2 mM Fe2+ and 1500 mA

The attack of \({^{ \bullet } {\text{OH}}}\) and BDD(\({^{ \bullet } {\text{OH}}}\)) on the cyclic structure causes its hydroxylation upon attack onto nitrogen atoms and/or –CH group (Lutterbeck et al. 2016), followed by ring cleavage with formation of carboxylic acids. This is demonstrated for 5-fluorouracil in Fig. 4A, where acetic and oxalic acids (as free molecules or complexed with Fe2+ ions) are accumulated since the beginning of the electrolyses and then progressively destroyed, in agreement with the low TOC remaining in the final solutions. The oxidation of the drug is accompanied by the release of heteroatoms. Figure 4A shows that F is almost completely released as F-, whereas nitrogenated ions (NH4 + and NO3 ) only account for less than 60% of the initial N, which can be explained by the formation of N-containing soluble organic matter along with the production of volatile products such as N2 and NxOy.
Fig. 4

By-products generated during the electro-Fenton treatment of 0.1 mM 5-fluorouracil with 0.2 mM Fe2+ at 300 mA. A Evolution of oxalic and acetic acids. B Accumulation of inorganic ions. The final solution contains no acids, and initial heteroatoms are accumulated as F along with low amounts of N-containing ions


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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Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Laboratoire Géomatériaux et Environnement (EA 4508), UPEMUniversité Paris-EstMarne-la-ValléeFrance
  2. 2.Laboratori d’Electroquímica dels Materials i del Medi Ambient, Departament de Química Física, Facultat de QuímicaUniversitat de BarcelonaBarcelonaSpain
  3. 3.Department of Civil and Mechanical EngineeringUniversity of Cassino and Southern LazioCassinoItaly

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