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Electrochemical detection and removal of pharmaceuticals in waste waters
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Electrochemical detection and removal of pharmaceuticals in waste waters
Bogdan Feier∗∗ , Anca Florea∗∗ , Cecilia Cristea and ∗ ˘ Robert Sandulescu The main classes of pharmaceuticals found in environmental samples, wastewaters included, contain various compounds such as antibiotics, antipyretics, analgesics, anti-inflammatories, antimicrobials and hormones. These compounds and their bioactive metabolites are continuously introduced into the aquatic systems at ng L−1 or pg L−1 levels by several routes including emission from production sites, direct disposal of drugs in households and hospitals, excretion after drug administration to humans and animals and water treatments in fish farms. Due to their toxicity and accumulation into living organism, their presence constitutes a serious environmental problem even at trace concentrations and, unfortunately, they are resistant to biological degradation processes, escaping almost intact from conventional wastewater treatments. Various detection methods using unmodified and modified electrodes with enzymes, antibodies and aptamers are presented, while the main part of this review is focusing on the removal of drugs from wastewaters by electrochemical methods. The main challenges as well as future trends regarding the electrochemical detection and removal methods are also pointed out. Address Analytical Chemistry Department, Faculty of Pharmacy, “Iuliu Hat¸ ieganu” University of Medicine and Pharmacy, 4 Pasteur Street, 400349 Cluj-Napoca, Romania ∗
˘ Corresponding author: Sandulescu, Robert ([email protected]) Authors with equal contribution.
∗∗
Current Opinion in Electrochemistry 2018, XX:XX–XX This review comes from a themed issue on Environmental Electrochemistry Edited by Nicole Jaffrezic-Renault and Christine Mousty For a complete overview see the Issue and the Editorial Available online XX XXXX 2018
Since the late 1990s pharmaceuticals and personal-care products have been the focus of global environmental researchers’ attention, in their view entering the environment through wastewater treatment plants (WWTPs), surface-waters or soils, following human and animal excretion or agricultural usage. In spite of the advanced knowledge about their therapeutic effects in humans and/or farm stocks, there is limited knowledge about their unintended effects in the environment. The main sources of water pollution with pharmaceuticals are drug manufacturing industry, animal wastes in live-stocks farming and human waste by hospitals or domestic activities. Pharmaceutical manufacturing plants either have their own complete on-site treatment systems of generated wastewater, or can install a pretreatment facility to remove the organic compounds and then send the partially treated wastewater to the municipal system. A greater source of pollution comes from hospitals, mainly from the drugs or metabolites cleared and excreted in the patients’ urine. A smaller portion comes from expired or unneeded drugs that are flushed unused down the sewage system. Another important source is the use of antibiotic and hormones in livestock. The wastewater from household activities is insignificant in term of drug pollution. The most frequently detected classes of pharmaceuticals found in surface water and even in groundwater include non-steroidal anti-inflammatory drugs (NSAIDs, such as diclofenac and ketoprofen), beta-blockers (e.g. atenolol), antibiotics (e.g. β-lactams, macrolides, fluoroquinolones, tetracyclines, sulfamides), neuroleptics (mainly carbamazepine, diazepam, fluoxetine), hormones (e.g. ethinylestradiol, 17-β-estradiol), and lipid regulators (e.g. bezafibrate, clofibric acid, gemfibrozil) [1•• ].
https://doi.org/10.1016/j.coelec.2018.06.012 2451-9103/© 2018 Elsevier B.V. All rights reserved.
Introduction Water pollution, one of the most serious environmental problems, is caused either by natural sources (soil erosion, decaying of organic matter) or by human activities such as industrial, agricultural and domestic actions. www.sciencedirect.com
The presence of these pharmaceuticals in surface and drinking water has numerous negative effects on humans and ecosystems. Pharmaceuticals in surface waters exhibit toxic effects on aquatic organisms while their presence in drinking water can cause an increase in the incidence of some diseases, e.g. cancer (female sex hormones). Antibiotics can lead to e.g. the increase in drug resistance of microorganisms, including pathogenic microorganisms. Pharmaceuticals in drinking water can pose a threat to infants, babies, the elderly, and people who suffer from kidney or liver failure and cancer. The occurrence of estrogens in drinking water can diminish men fertility and Current Opinion in Electrochemistry 2018, 000:1–11
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increase the incidence of breast and testicular cancer [2– 4]. Drugs present in drinking water i.e. anticancer drugs, can penetrate blood-placenta barrier, and thus cause teratogenic and embryotoxic effect, being particularly dangerous to pregnant women due to their cytotoxic activity [5,6]. Due to the above-mentioned reasons it is of utmost importance to accurately assess the presence of pharmaceuticals in surface and groundwater, as well as in drinking water, and to evaluate the impact on human health following long term exposure to various pharmaceuticals. This should also take into consideration the seasonal variability, bioaccumulation and potential degradation products/metabolites [7]. Following accurate identification of the polluting (classes of) pharmaceuticals, water treatment options can be envisaged to minimize or remove pharmaceuticals. Taking into consideration their broad range of physico-chemical properties a combination of different methods is usually required for effective water treatment [8]. This review presents the latest work on electrochemical detection of pharmaceuticals from environmental water samples and the electrochemical methods used for their efficient removal from these waters.
Currently used analytical methods There are currently no regulations regarding the admissible levels of pharmaceuticals in waters, air or soil, there are only few scientists’ recommendations available [9–11]. The detection of pharmaceutical in environmental samples is usually achieved by gas chromatography (GC) or high performance liquid chromatography (HPLC) separation of pretreated samples, followed by qualitative and quantitative analysis using various detectors [12]. The requirement of sample preparation is easier for HPLC than for GC, water sample being only filtered (usually 0.45 mm filter) prior to being directly injected into the HPLC. For specific compounds, the selection of analytical methods depends on the physical and chemical properties of the targeted chemicals [13•• ]. Other analytical techniques such as Raman spectroscopy [14,15], nuclear magnetic resonance [16] and electrochemical methods [17,18] can be also used to identify the traces of pharmaceuticals in environmental waters. For this techniques sample preparation (i.e. the extraction, purification and pre-concentration of the samples) is usually required, which is achieved by using solidphase extraction (SPE), liquid-liquid extraction (LLE), liquid-liquid micro-extraction (LLME) and solid-phase microextraction (SPME). The recently used combination of chromatography with mass spectrometry such as liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/ MS) and gas chromatography-mass spectrometry/mass spectrometry (GC–MS/MS) extend the Current Opinion in Electrochemistry 2018, 000:1–11
range of determination and identification of pharmaceutical with detection limits of ng L−1 . Some of the pharmaceuticals can accumulate and persist in waters e.g. erythromycin, while others are “pseudopersistent” e.g. diclofenac. A number of pharmaceuticals cannot be removed from drinking water treatment plants, showing that conventional removal methods might not be efficient enough. Other methods for their removal have been developed such as advanced oxidation processes (AOPs), involving photocatalysis, ozonation, Fenton and photo-Fenton oxidation, UV/H2 O2 oxidation, ionizing radiation, non-thermal plasma and sonolysis [19]. Some interesting approaches based on degradation with oxidoreductase enzymes present in species of fungi have also been described recently [20,21]. A great deal of attention has been focused on the application of electrochemical methods for water treatments, due to their ease of operation, low cost and amenability for a wide range of compounds including organic, inorganic or ionic species. Their only requirement is to remove large particles from water prior to their application, which is already done during the conventional treatment.
Pharmaceuticals detection with electrochemical methods Electrochemical sensors represent a reliable alternative to current methods for on-site detection of pharmaceuticals residues as they can be easily automated and miniaturized. Currently, there are few papers on the development of electrochemical strategies applied to the detection of pharmaceuticals in water samples. Most of the reported strategies are applied to foodstuff analysis, but the working principle can be easily further extended to water analysis, if further studies with interfering compounds from water are performed. There are several reviews that include electrochemical strategies for drug detection, in particular antibiotics, in foodstuff [22,23] or biological samples [24]. An overview of recent electrochemical methods involving modified or unmodified electrodes is summarizes in Figure 1 and is presented in detail below. With the latest increasing interest in fighting antimicrobial drug resistance a great deal of attention has been focused on detecting antibiotics in waters. A wide variety of antibodies are now present on the market encouraging the development of novel immunosensors able to detect antibiotics at low levels with high selectivity. Different assay formats can be explored to reach the desired performances. Merola et al. [25] developed an electrochemical immunosensor for sensitive detection on penicilin G and other beta-lactam antibiotics using two competitive assays. A H2 O2 electrode was employed as transducer. In the first format, specific anti-penicillin antibodies were immobilized on an Immobilon membrane www.sciencedirect.com
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Figure 1
Several modification strategies and electrochemical techniques for drug analysis.
that overlapped a cellulose acetate membrane placed on the lower end of the plastic cap of an amperometric electrode for H2 O2 . When the sample containing penicillin and penicillin labeled with hydrogen peroxidase via avidin-biotin linking was added, the antigens competed for the available sites of the immobilized antibody. In a second format the antigen was immobilized on the electrode membrane and penicillin and anti-penicillin antibody labeled with the enzyme were added in the system, following the same competition of immobilized and free penicillin for the antibody. This approach allowed to reach very low detection limits for beta-lactam antibiotics in the order of 10−10 M and was applied to river waste water analysis without any pretreatment. The sensor was also sensitive to dicloxacillin, amoxicillin, ampicillin and cefotaxime [25]. Aptamers have arisen in recent years as promising synthetic, and thus more stable and cheap, alternative to antibodies in the developments of biosensors. Yang et al. [26] developed an electrochemical aptasensors for the detection of ampicillin and sulfadimethoxine based on aptamer signaling probe displacement. The sensor achieved low limit of detection (LOD) in square wave voltammetry (SWV) measurements for the two antibiotics of 0.28 and 7 nM in spiked lake water. Feier et al developed a simple electrochemical method for the detection of cefalexin, a cephalosporin antibiotic www.sciencedirect.com
[17] and oxacillin, a penicillin antibiotic [18] from spiked river water, based on anodic oxidation at high potential by differential pulse voltammetry (DPV). Different electrode materials were tested and the best results were obtained with the bare boron-doped diamond electrode (BDDE), the high oxidation potential allowing the antibiotics detection with certain selectivity. The anodic oxidation of cefalexin and oxacillin was successfully adapted for flow injection analyses, with sensitive and reproducible successive DPV analyses of cefalexin and respectively of oxacillin, at different concentrations. The flow analyses allowed whole class detection, being able to determine the total amount of cephalosporins found in the sample, which was not possible by DPV, because of the different electrochemical behavior of different cephalosporin molecules. There is a growing interest in recent years in detecting simultaneously several compounds, resulting in shorter analysis times and lower costs, which is important for fast on-site tests. An electrochemical sensor for simultaneous detection of tartrazine, dexamethasone and diclofenac was developed by Oliveira et al. [27] using a hanging mercury drop electrode. The targets exhibit fast electrode kinetics that allowed their simultaneous detection at high scan rates without any further electrode modification, at low concentrations ranging from 2.8·10−8 M Current Opinion in Electrochemistry 2018, 000:1–11
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Table 1 Electrochemical strategies for pharmaceuticals detection.
Analyte
Detection method
Penicillin G (beta-lactams) Ampicillin Sulfadimethoxine Cefalexin (cephalosporins) Oxacillin (penicillins) Dexamethasone Diclofenac
Amperometry SWV DPV, amperometry DPV, amperometry SWV
Paracetamol
DPV
Metronidazole Paracetamol
LSV Amperometry
Sensor type
LOD (M)
Immunosensor Aptasensor Unmodified BDDE Unmodified BDDE Unmodified GC electrode GC/carbon nanoballs AgNPs/graphene Nafion/FeTPyPz
Water sample
Ref.
10 2.8·10−10 7·10−9 10−7 10−5 2.8·10−8 1.8·10−7
River waste water Lake water Spiked river water Spiked river water Wastewater
[25] [26] [17] [18] [27]
1.3·10−8 8·10−9
Natural water from creek Lake water River water
[28• ]
−10
2.8·10−8 10−6
[29• ] [30]
Legend: GC - glassy carbon; AgNPs - silver nanoparticles; FeRPyPz - iron tetrapyridino-porphyrazine; BDDE- boron doped diamond electrode; SWV- square wave voltammetry; DPV- differential pulse voltammetry; LSV- linear sweep voltammetry.
to 1.8·10−7 M. The method was successfully applied to quantify the contaminants in wastewater after solid-phase extraction, presenting high accuracy even in the presence of electroactive interferents. With the advancement of the field of nanomaterials, polymers, carbon and metal materials have been widely exploited in electrode modification, providing improved sensitivity and selectivity of biosensors. An interesting approach was developed by Raymundo-Pereira et al. [28• ] for the simultaneous detection of paracetamol and hydroquinone. A simple coating of glassy carbon electrodes with a homogenous film of Printex 6 L Carbon nanoballs (20-25 nm) allowed the detection of hydroquinone and paracetamol by DPV with detection limits of 1.3·10−8 and 8·10−9 M, respectively. The method proved to be as efficient as standard chromatography for the detection of these compounds in natural waters from creek. Electrode surface nanostructuring was also employed by Li et al. [29• ], in a sensor for the detection of metronidazole. By integrating silver nanoparticles decorated petal-like graphene hybrid 3D materials the sensor was able to detect concentration of metronidazole of 2.8·10−8 M and was applied to lake water samples analysis. Flow injection analysis (FIA) has been exploited lately in water analysis to provide automated control of sample handling, by introducing a reproducible sample volume into a continuously flowing carrier solution. FIA also improves convective mass control, matrix exchange and precision and avoids poisoning of electrode surface. Oliveira et al developed a sensor for paracetamol detection based on a biomimetic platform coupled with a FIA system. The system involved modifications of glassy carbon electrodes with Nafion doped with iron tetrapyridino-porphyrazine and achieved a LOD of 10−6 M [30]. Current Opinion in Electrochemistry 2018, 000:1–11
Electrochemical strategies applied for the detection of pharmaceuticals in various water samples found in the last few years are summarized in the Table 1.
Drug removal from waste and river waters by electrochemical methods The presence in the water bodies (wastewater, surface and ground water) of thousands of pharmaceutical molecules, at different concentrations can affect the quality of the water and can impact the supplies of drinking water, the ecosystems and the human health. Therefore, over the last decades, research efforts have been made at developing more effective technologies for the remediation of waters containing pharmaceuticals, their removal being achieved by three main methods: physical, biological and chemical [31]. The use of chlorine or chlorine dioxide is still the most used conventional treatment for disinfecting drinking waters, but many pharmaceuticals are not degraded by them. The common WWTPs comprise a primary system of physico-chemical treatments, which can remove some pharmaceuticals by adsorption, whereas others remain in the water, and secondary system that consists of a biological reactor formed by activated sludge, which presents a limited capacity to remove pharmaceutical products from urban wastewaters, since most of the compounds cannot be metabolized by microorganisms as source of carbon and may even inhibit the activity of the microorganisms or produce their bioaccumulation in the food chain. Since conventional treatment systems are unable to completely remove the pharmaceutical micropollutants present in urban wastewaters, more effective treatments www.sciencedirect.com
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Figure 2
Electrochemical methods for the conversion or complete degradation of pharmaceutical pollutants by direct electron transfer (A), by generation of •OH, H2 O2 or active chlorine species (B) and by EAOPs based on Fenton’s reaction (C) using “active” or “non-active” anodes (D).
are required. Tertiary water treatments may include: biological systems to remove nitrogen, ionic exchange to remove ions, chemical precipitation to remove phosphorus, distillation to remove volatile organic compounds, liquid–liquid extraction, adsorption on activated carbon to remove organic and inorganic pollutants and AOPs to remove toxic biorefractory organic compounds, based on ozonation, photooxidation, radiolysis and electrochemical processes [31]. Among the various technologies for the remediation of waters containing persistent organic pollutants, an increasing interest is presented for the electrochemical ones, with the so-called electrochemical advanced oxidation processes (EAOPs) being the most popular (Figure 2). Recent reviews have covered the electrochemical removal of the organic pollutants (pharmaceuticals included) from synthetic, real wastewaters or landfill leachates [32], by different technologies [33•• ,34,35• ], by electrochemical separation technologies [36], with the elucidation of the mechanisms of electro-oxidation degradation [37]. www.sciencedirect.com
The electrochemical techniques allow two approaches: the electrochemical conversion (the refractory organic pollutants are selectively transformed into biodegradable compounds) and the electrochemical combustion (the organic pollutants are mineralized). Zaghdoudi et al. has tested two electrochemical reduction processes aiming to reduce the dimetridazole, a nitroimidazole-based antibiotic, into more biodegradable by-products before implementing a biological process for its removal [38• ]. The EAOPs involve the oxidation of pollutants in an electrolytic cell by direct electron transfer between the molecule and the anode or by indirect or mediated oxidation with heterogeneous radicals formed from water discharge at the anode. Thus, the complete removal of ciprofloxacin, sulfamethoxazole and salbutamol was obtained by direct oxidation under galvanostatic conditions, using the BDD anode [39• ]. Current Opinion in Electrochemistry 2018, 000:1–11
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Due to the powerful oxidation effect of Ti/PbO2 , direct oxidation was the dominant mechanism in the electrochemical removal of carbamazepine from pharmaceutical wastewater, using Ti/PbO2 and carbon felt as working anode and working cathode, respectively [40]. The degradation of phenacetin in alkaline media using a three-dimensional reactor with particle electrodes involved first the removal of the branch chains mainly by direct oxidation, followed by indirect oxidation to ring opening products and finally mineralization to CO2 , H2 O [41]. When the wastewater contains chloride ions, these are directly oxidized at the anode, generating active chlorine species (Cl2 , HClO/ClO− and ClO2 − ) that can attack the organic pollutants. The indirect electro-oxidation with active chlorine was used for the degradation of carbamazepine using Nb/BDD or Ti/IrO2 as anodes, the oxidation being more effective with the Nb/BDD due to the increased production of •OH radicals and HClO, Cl• and ClO− [42• ]. Using the same degradation route of electrogenerated active chlorine, the initial concentration of six antibiotics belonging to three different classes (penicillins, cephalosporins, fluoroquinolones) decreased by more than 90% after treatment using an electrochemical system with a Ti/IrO2 anode and a Zr cathode in the presence of NaCl [43]. Degradation of the pharmaceuticals involves usually their oxidation by reactive oxygen species (ROS) produced at the surface of the anode as intermediates of oxidation of water to oxygen (Eq. (1)) [33]. The ROS include the highly reactive hydroxyl radicals (•OH), the second strongest oxidant known after fluorine, being able to degrade even highly recalcitrant organic pollutants, presenting a short life-time and self-elimination from the treatment system, and weaker oxidants like H2 O2 produced by dimerization of •OH and O3 formed from water discharge at the anode surface [33]. M + H2 O → M(• OH) +H+ + e−
(1)
A multiwalled carbon nanotubes (MWCNTs) electrode doped with CeO2 was prepared by electrodeposition and successfully used as anode for the degradation of ceftazidime, through hydroxyl radicals generated on the surface of the anode. The efficiency of the removal of ceftazidime from simulated wastewater was approximately 100% [44]. The electrochemical oxidation at BDD electrode was shown to be an effective technique for removing pharmaceuticals (iopromide, sulfamethoxazole, 17-alphaCurrent Opinion in Electrochemistry 2018, 000:1–11
ethinylestradiol, diclofenac) from simulated wastewater and real hospital effluent wastewater, but a slower degradation of transformation products was observed [45• ]. In EAOPs, H2 O2 could be in situ generated from the two-electron oxygen reduction reaction, which was then converted to •OH radicals in the role of cathode catalyst. To improve the efficiency of H2 O2 generation, cobalt sulfide/partly-graphitized carbon (Co9 S8 /PGC) composites were synthesized via simultaneous carbonization method and used as cathodes. Synergistic effect between Co9 S8 and PGC could improve the electron transfer efficiency and O2 mass transfer by increasing the contact interface area between electrode and electrolyte, leading to degradation rates of phenol and removal rate of ceftazidime of approximately 89% and 84% at 120 and 480 min, respectively [46• ]. The degradation of tetracaine by electrochemical oxidation with electrogenerated H2 O2 (EO-H2 O2 ) was tested using BDD, Pt, IrO2 -based or RuO2 -based anodes and air-diffusion cathode that allowed continuous H2 O2 electrogeneration. The removal of tetracaine from 0.050 M Na2 SO4 solution was much faster using BDD, while quicker pharmaceutical decay was found using the RuO2 based anode in the simulated matrix and the real urban wastewater [47]. EAOPs based on Fenton’s reaction (EF) leads to the formation of the powerful •OH from the reaction of Fe2+ with H2 O2 , comprising the in situ and continuous electrogeneration of H2 O2 at a carbonaceous cathode fed with pure oxygen or air, the addition of Fe2+ catalyst to the solution, and the cathodic reduction of Fe3+ to Fe2+ . When an undivided cell is used, the EF process also benefits of ROS produced at the anode. Three anti-inflammatory drugs were successfully removed from municipal wastewater by electro-Fenton process, achieving up to 90% total organic carbon (TOC) removal in the WWTP effluent after 3 h of reaction [48]. The photoelectro-Fenton (PEF) proved very efficient for the degradation of the municipal wastewater after secondary treatment spiked with 5.0 mg L−1 of trimethoprim (TMP). It was tested by applying various AOPs and EAOPs, like UVC, H2 O2 /UVC, anodic oxidation (AO), AO-H2 O2 , AO-H2 O2 /UVC and photoelectro-Fenton using either UVC or UVA radiation (PEF-UVC or PEFUVA). The efficiency of processes to remove TMP showed that UVC is the most efficient. The bio-electroFenton process, forming the strong oxidant •OH using the electrons derived from bacterial oxidation of organic substrate was used for the treatment of four different NSAIDs, with removal efficiencies of 61–97% in 5 h reaction time, but the results obtained with real wastewater www.sciencedirect.com
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The removal of several pharmaceuticals from wastewaters.
Process
Electrochemical conditions/ Electrode
Degradation efficiency (%)
Ref.
Dimetridazole
Artificial solutions
A home-made flow cell. Graphite felt as working electrode
Total degradation (conversion yield = 99.5%); 81% of the TOC was removed in direct electrolysis
[38• ]
Ciprofloxacin, sulfamethoxa- zole, salbutamol Carbamazepine
Wastewater
Direct electrochemical reduction; indirect electrochemical reduction in the presence of titanocene dichloride; biological treat-ment with activated sludge Direct oxidation
BDD anode
Complete removal
[39• ]
Applying 1.7 A of current intensity during 88 min of treatment time in the presence of 500 mg/L of Na2 SO4 / Ti/PbO2 - working anode and CF working cathode 3-D electro-catalytic reactor
75%
[40]
Removal
[41]
The best operational conditions: current of 1.0 A during 12.45 min using a concentration of 14 mM of NaCl, with CBZ / Nb/BDD or Ti/IrO2 as anodes
Degradation efficiency of 88.70%
[42• ]
Electrochemical system with a Ti/IrO2 anode and a Zr cathode in the presence of NaCl (0.05 µM)
>90%
[43]
Electrolysis time: 60 min; supporting electrolyte solution: 1 g L−1 Na2 SO4 ; current density: 3 mAcm−2 ; electrode spacing of 1 cm / CeO2 /MWCNTs
100%
[44]
Pharmaceutical wastewater
Direct oxidation
Phenacetin
Alkaline media
Carbamazepine
Cephalexin, cephadroxyl, cloxacillin, oxacillin, ciprofloxacin, norfloxacin
Real wastewater from the secondary settler of an activated sludge treatment plant and spiked with CBZ and NaCl Synthetic hospital wastewater and seawater containing one antibiotic
Direct oxidation and indirect oxidation Indirect oxidation by electro-generated active chlorine had the main contribution.
Ceftazidime
Simulated wastewater
The attack of electro-generated active chlorine was found to be the main degradation route. The attack of hydroxyl radicals electro-generated on the surface of the anode
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Table 2
Electrochemical conditions/ Electrode
Degradation efficiency (%)
Ref.
Iopromide, sulfamethoxazo-le, 17alpha-ethinylestradiol, diclofenac Ceftazidime
Simulated waste-water and real hospital effluent wastewater
[45• ]
84%
[46• ]
Tetracaine
0.05 M Na2 SO4 , real urban waste-water and a simulated matrix
electrochemical oxidation with electrogenerated H2 O2
> 50% of TOC abatement after 360 min of electrolysis
[47]
Mixture of diclofenac, ibuprofen and naproxen Ketoprofen, diclofenac, ibuprofen, naproxen
Deionized water and WWTP effluent
Electro-Fenton process
The experimental set-up consisted of a flow-through electrochemical cell, a circulation tank and a centrifugal pump / BDD anode Cobalt sulfide/partly-graphitized carbon (Co9 S8 /PGC) composites as cathode Undivided cell with a 3 cm2 BDD, Pt, IrO2 -based or RuO2 -based anode and a 3 cm2 air-diffusion cathode that allowed continuous H2 O2 electrogeneration / BDD, Pt, IrO2 -based or RuO2 -based anode EF with a current density of 40 mA cm−2 and 0.3 mmol Fe2+ L−1
100%
Bio-refractory organic wastewater
The attack of hydroxyl radicals electrogenerated on the surface of the anode. H2 O2 generated from the 2e− oxygen reduction reaction
Up to 90%
[48]
Real wastewater
Bio-electro-Fenton process
Ketoprofen: 59–61%, diclofenac: 87-97%, ibupro- fen:80–86%, naproxen:75–81%
[49• ]
Amoxicillin
Ultrapure water
Close to 100%
[50• ]
Naproxen
Artificial solution
The attack of hydroxyl radicals electrogenerated on the surface of the anode Different EAOPs: EO-H2 O2 , EF, PEF
Optimum parameters: pH=2, Fe2+ =7.5 mM, air-flow=8 mL min−1 , E = 0.3 V / A laboratory scale rectangular bio-electrochemical system consisting of two chambers, based on non-conducting polycarbonate sheets Carbon-felt, carbon fiber, carbon-graphite, platinum, lead dioxide, dimensionally stable anode (DSA), Ti/RuO2–IrO2 and BDD Pt, IrO2-based, RuO2-based and BDD
Total mineralization with BDD in PEF
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Table 2 (continued)
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showed lower removal rate constants than with distilled water matrices [49• ]. The anode material has a strong influence on the selectivity and efficiency of the degradation process, their different behavior being explained by a model that assumes the existence of ‘‘active’’ and ‘‘non-active’’ anodes. Both kinds of anodes (M) oxidize the water forming the physisorbed hydroxyl radical (M(•OH)). This radical interacts strongly with the surface of the ‘‘active’’ anodes, being transformed into the chemisorbed “active oxygen” or superoxide MO, with the MO/M pair being a mediator in the electrochemical conversion of organic compounds; the surface of “non-active oxygen” anodes interact weakly with M(•OH) and this radical directly reacts with organics until total mineralization is achieved. Ruthenium dioxide, iridium dioxide, platinum, graphite and other sp2 carbon-based electrodes are typical examples of “active anodes”, while lead dioxide, tin dioxide, BDD and sub-stoichiometric TiO2 electrodes can be considered as “non-active” electrodes, with the BDD anode being the most potent “non-active” anode known, hence the most suitable anode for AO [31]. This was proved by a study testing the electro-oxidation capacities for the destruction of amoxicillin (AMX) of several electrode materials: carbon-felt, carbon fiber, carbon-graphite, platinum, lead dioxide, dimensionally stable anode (DSA), Ti/RuO2–IrO2 and BDD, with the latter being the best anode material for the large current densities due to generation of high amount of different oxidants, leading to almost complete mineralization of AMX solution. Platinum and carbon felt showed a relatively good oxidation behavior compared to carbon-fiber and carbon-graphite and DSA was found to be the less efficient electrode [50• ].
9
Several studies regarding the treatment of wastewaters polluted with pharmaceuticals by the application of different electrochemical procedures are presented in Table 2.
Conclusion and perspectives In this review, we have described the recent works on electrochemical based methods for detection and removal of several drugs classes. While for the detection the conventional separation techniques are still the golden standard, few attempts were reported in the last two years on the electrochemical detection of drugs. An increased interest was observed for the detection of antibiotics and hormones, which presents toxic effect with accumulation in waste waters creating bacteria with high resistance to the commonly used antibiotics or disrupt the hormonal balance. Due to the high oxidation potential of the most classes of antibiotics, the BDD electrode as well as biomimetic elements (aptamers and molecular imprinted polymers based sensors) are intensively used. Nevertheless, the detection procedures are far from being applicable on real samples due to the high amount of organics that are currently found in waste waters and low concentration of drugs. Preconcentration methods or FIA could be envisaged when working on waste waters. Anyway, the things are complicated due to the lack of harmonized legislation regarding the maximum admissible limits of various classes of drugs, the lack of standardized methods for sampling and pretreatment of waste waters from a country to another, the deficiency in electrode materials (only BDD proved to be a suitable material for high oxidation potentials necessary to detect and remove drugs), the necessary improvement of the detection sensitivity and selectivity.
Multi-walled carbon nanotubes (MWCNTs), Pt nanoparticles (Pt NPs), and PtRu alloy were used to synthesize three types of cheap and effective anodes based on commercial conductive glass for the degradation of ibuprofen. Addition of MWCNTs effectively reduced the grain size of electrocatalyst and EAOPs with the anode based on bimetallic PtRu nanoparticles were very effective due to advantages of the higher capacitance, catalytic ability at less positive voltage and stability [51].
Electrochemical methods are also successfully employed as effective technologies for the remediation of waters containing pharmaceutical pollutants. Extensive research has been made in recent years on pharmaceuticals removal from waters by electrochemical conversion an combustion employing strategies such as direct electron transfer, generation of •OH, H2 O2 or active chlorine species, EAOPs based on Fenton’s reaction or using “active” or “non-active” anodes to name a few.
The naproxen degradation was evaluated using different anodes (Pt, IrO2-based, RuO2-based and BDD) and EAOPs. Regardless of the anode, it was obtained this growing oxidation power: electro generated H2 O2 (EOH2 O2 ) < electro-Phenton (EF) < PEF. The IrO2 -based anode led to greater mineralization in EO-H2 O2 and EF, BDD better in PEF (total mineralization). In PEF, the naproxen concentration decay in PEF, it was enhanced in the sequence: RuO2 -based < Pt < BDD < IrO2 -based [52].
Still, electrochemical detection methods have certain advantages over the analytical methods currently used for drugs in waste waters like: low limits of detection, simple instrumentation, in situ analysis, cost of analysis and of electrochemical equipments, and no need for trained personal.
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Acknowledgments This work was supported by a grant of the Romanian National Authority for Scientific Research and Innovation, CNCS/CCCDI-UEFISCDI, project number PN-III-P2-2.1-PED-2016-0172, within PNCDI III. Also, this work was supported by a grant of Ministry of Research and Innovation, CNCS Current Opinion in Electrochemistry 2018, 000:1–11
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38. Zaghdoudi M, Fourcade F, Soutrel I, Floner D, Amrane A, • Maghraoui-Meherzi H, Geneste F: Direct and indirect electrochemical reduction prior to a biological treatment for dimetridazole removal. J Hazard Mater 2017, 335:10–17. This study shows the utility of an electrochemical conversion step in the process of degradation of pharmaceuticals with low biodegradability. 39. Lan Y, Coetsier C, Causserand C, Serrano KG: An experimental • and modelling study of the electrochemical oxidation of pharmaceuticals using a boron-doped diamond anode. Chem Eng J 2018, 333:486–494. The complete removal of ciprofloxacin, sulfamethoxazole, salbutamol from real wastewater was achieved by direct oxidation using the BDD anode. 40. Guitaya L, Azaïs A, Zaviska F, Drogui P, Blais J-F, Gourich B: Electrochemical oxidation as treatment for contaminated wastewaters by carbamazepine: process optimization through response surface methodology. Water Air Soil Pollut 2017, 228:384. 41. Xiao MS, Zhang YG: Electro-catalytic oxidation of phenacetin with a three-dimensional reactor: Degradation pathway and removal mechanism. Chemosphere 2016, 152:17–22. 42. García-Espinoza JD, Mijaylova-Nacheva P, Aviles-Flores M: • Electrochemical carbamazepine degradation: Effect of the generated active chlorine, transformation pathways and toxicity. Chemosphere 2018, 192:142–151. Indirect oxidation by electro-generated active chlorine at different electrodes was used for efficient degradation of carbamazepine from real wastewater from the secondary settler of an activated sludge treatment plant.
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Current Opinion in Electrochemistry 2018, 000:1–11
Please cite this article as: Feier et al., Electrochemical detection and removal of pharmaceuticals in waste waters, Current Opinion in Electrochemistry (2018), https://doi.org/10.1016/j.coelec.2018.06.012
Electrochemical detection and removal of pharmaceuticals in waste waters
Bogdan Feier∗∗ , Anca Florea∗∗ , Cecilia Cristea and ∗ ˘ Robert Sandulescu The main classes of pharmaceuticals found in environmental samples, wastewaters included, contain various compounds such as antibiotics, antipyretics, analgesics, anti-inflammatories, antimicrobials and hormones. These compounds and their bioactive metabolites are continuously introduced into the aquatic systems at ng L−1 or pg L−1 levels by several routes including emission from production sites, direct disposal of drugs in households and hospitals, excretion after drug administration to humans and animals and water treatments in fish farms. Due to their toxicity and accumulation into living organism, their presence constitutes a serious environmental problem even at trace concentrations and, unfortunately, they are resistant to biological degradation processes, escaping almost intact from conventional wastewater treatments. Various detection methods using unmodified and modified electrodes with enzymes, antibodies and aptamers are presented, while the main part of this review is focusing on the removal of drugs from wastewaters by electrochemical methods. The main challenges as well as future trends regarding the electrochemical detection and removal methods are also pointed out. Address Analytical Chemistry Department, Faculty of Pharmacy, “Iuliu Hat¸ ieganu” University of Medicine and Pharmacy, 4 Pasteur Street, 400349 Cluj-Napoca, Romania ∗
˘ Corresponding author: Sandulescu, Robert ([email protected]) Authors with equal contribution.
∗∗
Current Opinion in Electrochemistry 2018, XX:XX–XX This review comes from a themed issue on Environmental Electrochemistry Edited by Nicole Jaffrezic-Renault and Christine Mousty For a complete overview see the Issue and the Editorial Available online XX XXXX 2018
Since the late 1990s pharmaceuticals and personal-care products have been the focus of global environmental researchers’ attention, in their view entering the environment through wastewater treatment plants (WWTPs), surface-waters or soils, following human and animal excretion or agricultural usage. In spite of the advanced knowledge about their therapeutic effects in humans and/or farm stocks, there is limited knowledge about their unintended effects in the environment. The main sources of water pollution with pharmaceuticals are drug manufacturing industry, animal wastes in live-stocks farming and human waste by hospitals or domestic activities. Pharmaceutical manufacturing plants either have their own complete on-site treatment systems of generated wastewater, or can install a pretreatment facility to remove the organic compounds and then send the partially treated wastewater to the municipal system. A greater source of pollution comes from hospitals, mainly from the drugs or metabolites cleared and excreted in the patients’ urine. A smaller portion comes from expired or unneeded drugs that are flushed unused down the sewage system. Another important source is the use of antibiotic and hormones in livestock. The wastewater from household activities is insignificant in term of drug pollution. The most frequently detected classes of pharmaceuticals found in surface water and even in groundwater include non-steroidal anti-inflammatory drugs (NSAIDs, such as diclofenac and ketoprofen), beta-blockers (e.g. atenolol), antibiotics (e.g. β-lactams, macrolides, fluoroquinolones, tetracyclines, sulfamides), neuroleptics (mainly carbamazepine, diazepam, fluoxetine), hormones (e.g. ethinylestradiol, 17-β-estradiol), and lipid regulators (e.g. bezafibrate, clofibric acid, gemfibrozil) [1•• ].
https://doi.org/10.1016/j.coelec.2018.06.012 2451-9103/© 2018 Elsevier B.V. All rights reserved.
Introduction Water pollution, one of the most serious environmental problems, is caused either by natural sources (soil erosion, decaying of organic matter) or by human activities such as industrial, agricultural and domestic actions. www.sciencedirect.com
The presence of these pharmaceuticals in surface and drinking water has numerous negative effects on humans and ecosystems. Pharmaceuticals in surface waters exhibit toxic effects on aquatic organisms while their presence in drinking water can cause an increase in the incidence of some diseases, e.g. cancer (female sex hormones). Antibiotics can lead to e.g. the increase in drug resistance of microorganisms, including pathogenic microorganisms. Pharmaceuticals in drinking water can pose a threat to infants, babies, the elderly, and people who suffer from kidney or liver failure and cancer. The occurrence of estrogens in drinking water can diminish men fertility and Current Opinion in Electrochemistry 2018, 000:1–11
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increase the incidence of breast and testicular cancer [2– 4]. Drugs present in drinking water i.e. anticancer drugs, can penetrate blood-placenta barrier, and thus cause teratogenic and embryotoxic effect, being particularly dangerous to pregnant women due to their cytotoxic activity [5,6]. Due to the above-mentioned reasons it is of utmost importance to accurately assess the presence of pharmaceuticals in surface and groundwater, as well as in drinking water, and to evaluate the impact on human health following long term exposure to various pharmaceuticals. This should also take into consideration the seasonal variability, bioaccumulation and potential degradation products/metabolites [7]. Following accurate identification of the polluting (classes of) pharmaceuticals, water treatment options can be envisaged to minimize or remove pharmaceuticals. Taking into consideration their broad range of physico-chemical properties a combination of different methods is usually required for effective water treatment [8]. This review presents the latest work on electrochemical detection of pharmaceuticals from environmental water samples and the electrochemical methods used for their efficient removal from these waters.
Currently used analytical methods There are currently no regulations regarding the admissible levels of pharmaceuticals in waters, air or soil, there are only few scientists’ recommendations available [9–11]. The detection of pharmaceutical in environmental samples is usually achieved by gas chromatography (GC) or high performance liquid chromatography (HPLC) separation of pretreated samples, followed by qualitative and quantitative analysis using various detectors [12]. The requirement of sample preparation is easier for HPLC than for GC, water sample being only filtered (usually 0.45 mm filter) prior to being directly injected into the HPLC. For specific compounds, the selection of analytical methods depends on the physical and chemical properties of the targeted chemicals [13•• ]. Other analytical techniques such as Raman spectroscopy [14,15], nuclear magnetic resonance [16] and electrochemical methods [17,18] can be also used to identify the traces of pharmaceuticals in environmental waters. For this techniques sample preparation (i.e. the extraction, purification and pre-concentration of the samples) is usually required, which is achieved by using solidphase extraction (SPE), liquid-liquid extraction (LLE), liquid-liquid micro-extraction (LLME) and solid-phase microextraction (SPME). The recently used combination of chromatography with mass spectrometry such as liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/ MS) and gas chromatography-mass spectrometry/mass spectrometry (GC–MS/MS) extend the Current Opinion in Electrochemistry 2018, 000:1–11
range of determination and identification of pharmaceutical with detection limits of ng L−1 . Some of the pharmaceuticals can accumulate and persist in waters e.g. erythromycin, while others are “pseudopersistent” e.g. diclofenac. A number of pharmaceuticals cannot be removed from drinking water treatment plants, showing that conventional removal methods might not be efficient enough. Other methods for their removal have been developed such as advanced oxidation processes (AOPs), involving photocatalysis, ozonation, Fenton and photo-Fenton oxidation, UV/H2 O2 oxidation, ionizing radiation, non-thermal plasma and sonolysis [19]. Some interesting approaches based on degradation with oxidoreductase enzymes present in species of fungi have also been described recently [20,21]. A great deal of attention has been focused on the application of electrochemical methods for water treatments, due to their ease of operation, low cost and amenability for a wide range of compounds including organic, inorganic or ionic species. Their only requirement is to remove large particles from water prior to their application, which is already done during the conventional treatment.
Pharmaceuticals detection with electrochemical methods Electrochemical sensors represent a reliable alternative to current methods for on-site detection of pharmaceuticals residues as they can be easily automated and miniaturized. Currently, there are few papers on the development of electrochemical strategies applied to the detection of pharmaceuticals in water samples. Most of the reported strategies are applied to foodstuff analysis, but the working principle can be easily further extended to water analysis, if further studies with interfering compounds from water are performed. There are several reviews that include electrochemical strategies for drug detection, in particular antibiotics, in foodstuff [22,23] or biological samples [24]. An overview of recent electrochemical methods involving modified or unmodified electrodes is summarizes in Figure 1 and is presented in detail below. With the latest increasing interest in fighting antimicrobial drug resistance a great deal of attention has been focused on detecting antibiotics in waters. A wide variety of antibodies are now present on the market encouraging the development of novel immunosensors able to detect antibiotics at low levels with high selectivity. Different assay formats can be explored to reach the desired performances. Merola et al. [25] developed an electrochemical immunosensor for sensitive detection on penicilin G and other beta-lactam antibiotics using two competitive assays. A H2 O2 electrode was employed as transducer. In the first format, specific anti-penicillin antibodies were immobilized on an Immobilon membrane www.sciencedirect.com
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Figure 1
Several modification strategies and electrochemical techniques for drug analysis.
that overlapped a cellulose acetate membrane placed on the lower end of the plastic cap of an amperometric electrode for H2 O2 . When the sample containing penicillin and penicillin labeled with hydrogen peroxidase via avidin-biotin linking was added, the antigens competed for the available sites of the immobilized antibody. In a second format the antigen was immobilized on the electrode membrane and penicillin and anti-penicillin antibody labeled with the enzyme were added in the system, following the same competition of immobilized and free penicillin for the antibody. This approach allowed to reach very low detection limits for beta-lactam antibiotics in the order of 10−10 M and was applied to river waste water analysis without any pretreatment. The sensor was also sensitive to dicloxacillin, amoxicillin, ampicillin and cefotaxime [25]. Aptamers have arisen in recent years as promising synthetic, and thus more stable and cheap, alternative to antibodies in the developments of biosensors. Yang et al. [26] developed an electrochemical aptasensors for the detection of ampicillin and sulfadimethoxine based on aptamer signaling probe displacement. The sensor achieved low limit of detection (LOD) in square wave voltammetry (SWV) measurements for the two antibiotics of 0.28 and 7 nM in spiked lake water. Feier et al developed a simple electrochemical method for the detection of cefalexin, a cephalosporin antibiotic www.sciencedirect.com
[17] and oxacillin, a penicillin antibiotic [18] from spiked river water, based on anodic oxidation at high potential by differential pulse voltammetry (DPV). Different electrode materials were tested and the best results were obtained with the bare boron-doped diamond electrode (BDDE), the high oxidation potential allowing the antibiotics detection with certain selectivity. The anodic oxidation of cefalexin and oxacillin was successfully adapted for flow injection analyses, with sensitive and reproducible successive DPV analyses of cefalexin and respectively of oxacillin, at different concentrations. The flow analyses allowed whole class detection, being able to determine the total amount of cephalosporins found in the sample, which was not possible by DPV, because of the different electrochemical behavior of different cephalosporin molecules. There is a growing interest in recent years in detecting simultaneously several compounds, resulting in shorter analysis times and lower costs, which is important for fast on-site tests. An electrochemical sensor for simultaneous detection of tartrazine, dexamethasone and diclofenac was developed by Oliveira et al. [27] using a hanging mercury drop electrode. The targets exhibit fast electrode kinetics that allowed their simultaneous detection at high scan rates without any further electrode modification, at low concentrations ranging from 2.8·10−8 M Current Opinion in Electrochemistry 2018, 000:1–11
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Table 1 Electrochemical strategies for pharmaceuticals detection.
Analyte
Detection method
Penicillin G (beta-lactams) Ampicillin Sulfadimethoxine Cefalexin (cephalosporins) Oxacillin (penicillins) Dexamethasone Diclofenac
Amperometry SWV DPV, amperometry DPV, amperometry SWV
Paracetamol
DPV
Metronidazole Paracetamol
LSV Amperometry
Sensor type
LOD (M)
Immunosensor Aptasensor Unmodified BDDE Unmodified BDDE Unmodified GC electrode GC/carbon nanoballs AgNPs/graphene Nafion/FeTPyPz
Water sample
Ref.
10 2.8·10−10 7·10−9 10−7 10−5 2.8·10−8 1.8·10−7
River waste water Lake water Spiked river water Spiked river water Wastewater
[25] [26] [17] [18] [27]
1.3·10−8 8·10−9
Natural water from creek Lake water River water
[28• ]
−10
2.8·10−8 10−6
[29• ] [30]
Legend: GC - glassy carbon; AgNPs - silver nanoparticles; FeRPyPz - iron tetrapyridino-porphyrazine; BDDE- boron doped diamond electrode; SWV- square wave voltammetry; DPV- differential pulse voltammetry; LSV- linear sweep voltammetry.
to 1.8·10−7 M. The method was successfully applied to quantify the contaminants in wastewater after solid-phase extraction, presenting high accuracy even in the presence of electroactive interferents. With the advancement of the field of nanomaterials, polymers, carbon and metal materials have been widely exploited in electrode modification, providing improved sensitivity and selectivity of biosensors. An interesting approach was developed by Raymundo-Pereira et al. [28• ] for the simultaneous detection of paracetamol and hydroquinone. A simple coating of glassy carbon electrodes with a homogenous film of Printex 6 L Carbon nanoballs (20-25 nm) allowed the detection of hydroquinone and paracetamol by DPV with detection limits of 1.3·10−8 and 8·10−9 M, respectively. The method proved to be as efficient as standard chromatography for the detection of these compounds in natural waters from creek. Electrode surface nanostructuring was also employed by Li et al. [29• ], in a sensor for the detection of metronidazole. By integrating silver nanoparticles decorated petal-like graphene hybrid 3D materials the sensor was able to detect concentration of metronidazole of 2.8·10−8 M and was applied to lake water samples analysis. Flow injection analysis (FIA) has been exploited lately in water analysis to provide automated control of sample handling, by introducing a reproducible sample volume into a continuously flowing carrier solution. FIA also improves convective mass control, matrix exchange and precision and avoids poisoning of electrode surface. Oliveira et al developed a sensor for paracetamol detection based on a biomimetic platform coupled with a FIA system. The system involved modifications of glassy carbon electrodes with Nafion doped with iron tetrapyridino-porphyrazine and achieved a LOD of 10−6 M [30]. Current Opinion in Electrochemistry 2018, 000:1–11
Electrochemical strategies applied for the detection of pharmaceuticals in various water samples found in the last few years are summarized in the Table 1.
Drug removal from waste and river waters by electrochemical methods The presence in the water bodies (wastewater, surface and ground water) of thousands of pharmaceutical molecules, at different concentrations can affect the quality of the water and can impact the supplies of drinking water, the ecosystems and the human health. Therefore, over the last decades, research efforts have been made at developing more effective technologies for the remediation of waters containing pharmaceuticals, their removal being achieved by three main methods: physical, biological and chemical [31]. The use of chlorine or chlorine dioxide is still the most used conventional treatment for disinfecting drinking waters, but many pharmaceuticals are not degraded by them. The common WWTPs comprise a primary system of physico-chemical treatments, which can remove some pharmaceuticals by adsorption, whereas others remain in the water, and secondary system that consists of a biological reactor formed by activated sludge, which presents a limited capacity to remove pharmaceutical products from urban wastewaters, since most of the compounds cannot be metabolized by microorganisms as source of carbon and may even inhibit the activity of the microorganisms or produce their bioaccumulation in the food chain. Since conventional treatment systems are unable to completely remove the pharmaceutical micropollutants present in urban wastewaters, more effective treatments www.sciencedirect.com
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Figure 2
Electrochemical methods for the conversion or complete degradation of pharmaceutical pollutants by direct electron transfer (A), by generation of •OH, H2 O2 or active chlorine species (B) and by EAOPs based on Fenton’s reaction (C) using “active” or “non-active” anodes (D).
are required. Tertiary water treatments may include: biological systems to remove nitrogen, ionic exchange to remove ions, chemical precipitation to remove phosphorus, distillation to remove volatile organic compounds, liquid–liquid extraction, adsorption on activated carbon to remove organic and inorganic pollutants and AOPs to remove toxic biorefractory organic compounds, based on ozonation, photooxidation, radiolysis and electrochemical processes [31]. Among the various technologies for the remediation of waters containing persistent organic pollutants, an increasing interest is presented for the electrochemical ones, with the so-called electrochemical advanced oxidation processes (EAOPs) being the most popular (Figure 2). Recent reviews have covered the electrochemical removal of the organic pollutants (pharmaceuticals included) from synthetic, real wastewaters or landfill leachates [32], by different technologies [33•• ,34,35• ], by electrochemical separation technologies [36], with the elucidation of the mechanisms of electro-oxidation degradation [37]. www.sciencedirect.com
The electrochemical techniques allow two approaches: the electrochemical conversion (the refractory organic pollutants are selectively transformed into biodegradable compounds) and the electrochemical combustion (the organic pollutants are mineralized). Zaghdoudi et al. has tested two electrochemical reduction processes aiming to reduce the dimetridazole, a nitroimidazole-based antibiotic, into more biodegradable by-products before implementing a biological process for its removal [38• ]. The EAOPs involve the oxidation of pollutants in an electrolytic cell by direct electron transfer between the molecule and the anode or by indirect or mediated oxidation with heterogeneous radicals formed from water discharge at the anode. Thus, the complete removal of ciprofloxacin, sulfamethoxazole and salbutamol was obtained by direct oxidation under galvanostatic conditions, using the BDD anode [39• ]. Current Opinion in Electrochemistry 2018, 000:1–11
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Due to the powerful oxidation effect of Ti/PbO2 , direct oxidation was the dominant mechanism in the electrochemical removal of carbamazepine from pharmaceutical wastewater, using Ti/PbO2 and carbon felt as working anode and working cathode, respectively [40]. The degradation of phenacetin in alkaline media using a three-dimensional reactor with particle electrodes involved first the removal of the branch chains mainly by direct oxidation, followed by indirect oxidation to ring opening products and finally mineralization to CO2 , H2 O [41]. When the wastewater contains chloride ions, these are directly oxidized at the anode, generating active chlorine species (Cl2 , HClO/ClO− and ClO2 − ) that can attack the organic pollutants. The indirect electro-oxidation with active chlorine was used for the degradation of carbamazepine using Nb/BDD or Ti/IrO2 as anodes, the oxidation being more effective with the Nb/BDD due to the increased production of •OH radicals and HClO, Cl• and ClO− [42• ]. Using the same degradation route of electrogenerated active chlorine, the initial concentration of six antibiotics belonging to three different classes (penicillins, cephalosporins, fluoroquinolones) decreased by more than 90% after treatment using an electrochemical system with a Ti/IrO2 anode and a Zr cathode in the presence of NaCl [43]. Degradation of the pharmaceuticals involves usually their oxidation by reactive oxygen species (ROS) produced at the surface of the anode as intermediates of oxidation of water to oxygen (Eq. (1)) [33]. The ROS include the highly reactive hydroxyl radicals (•OH), the second strongest oxidant known after fluorine, being able to degrade even highly recalcitrant organic pollutants, presenting a short life-time and self-elimination from the treatment system, and weaker oxidants like H2 O2 produced by dimerization of •OH and O3 formed from water discharge at the anode surface [33]. M + H2 O → M(• OH) +H+ + e−
(1)
A multiwalled carbon nanotubes (MWCNTs) electrode doped with CeO2 was prepared by electrodeposition and successfully used as anode for the degradation of ceftazidime, through hydroxyl radicals generated on the surface of the anode. The efficiency of the removal of ceftazidime from simulated wastewater was approximately 100% [44]. The electrochemical oxidation at BDD electrode was shown to be an effective technique for removing pharmaceuticals (iopromide, sulfamethoxazole, 17-alphaCurrent Opinion in Electrochemistry 2018, 000:1–11
ethinylestradiol, diclofenac) from simulated wastewater and real hospital effluent wastewater, but a slower degradation of transformation products was observed [45• ]. In EAOPs, H2 O2 could be in situ generated from the two-electron oxygen reduction reaction, which was then converted to •OH radicals in the role of cathode catalyst. To improve the efficiency of H2 O2 generation, cobalt sulfide/partly-graphitized carbon (Co9 S8 /PGC) composites were synthesized via simultaneous carbonization method and used as cathodes. Synergistic effect between Co9 S8 and PGC could improve the electron transfer efficiency and O2 mass transfer by increasing the contact interface area between electrode and electrolyte, leading to degradation rates of phenol and removal rate of ceftazidime of approximately 89% and 84% at 120 and 480 min, respectively [46• ]. The degradation of tetracaine by electrochemical oxidation with electrogenerated H2 O2 (EO-H2 O2 ) was tested using BDD, Pt, IrO2 -based or RuO2 -based anodes and air-diffusion cathode that allowed continuous H2 O2 electrogeneration. The removal of tetracaine from 0.050 M Na2 SO4 solution was much faster using BDD, while quicker pharmaceutical decay was found using the RuO2 based anode in the simulated matrix and the real urban wastewater [47]. EAOPs based on Fenton’s reaction (EF) leads to the formation of the powerful •OH from the reaction of Fe2+ with H2 O2 , comprising the in situ and continuous electrogeneration of H2 O2 at a carbonaceous cathode fed with pure oxygen or air, the addition of Fe2+ catalyst to the solution, and the cathodic reduction of Fe3+ to Fe2+ . When an undivided cell is used, the EF process also benefits of ROS produced at the anode. Three anti-inflammatory drugs were successfully removed from municipal wastewater by electro-Fenton process, achieving up to 90% total organic carbon (TOC) removal in the WWTP effluent after 3 h of reaction [48]. The photoelectro-Fenton (PEF) proved very efficient for the degradation of the municipal wastewater after secondary treatment spiked with 5.0 mg L−1 of trimethoprim (TMP). It was tested by applying various AOPs and EAOPs, like UVC, H2 O2 /UVC, anodic oxidation (AO), AO-H2 O2 , AO-H2 O2 /UVC and photoelectro-Fenton using either UVC or UVA radiation (PEF-UVC or PEFUVA). The efficiency of processes to remove TMP showed that UVC is the most efficient. The bio-electroFenton process, forming the strong oxidant •OH using the electrons derived from bacterial oxidation of organic substrate was used for the treatment of four different NSAIDs, with removal efficiencies of 61–97% in 5 h reaction time, but the results obtained with real wastewater www.sciencedirect.com
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The removal of several pharmaceuticals from wastewaters.
Process
Electrochemical conditions/ Electrode
Degradation efficiency (%)
Ref.
Dimetridazole
Artificial solutions
A home-made flow cell. Graphite felt as working electrode
Total degradation (conversion yield = 99.5%); 81% of the TOC was removed in direct electrolysis
[38• ]
Ciprofloxacin, sulfamethoxa- zole, salbutamol Carbamazepine
Wastewater
Direct electrochemical reduction; indirect electrochemical reduction in the presence of titanocene dichloride; biological treat-ment with activated sludge Direct oxidation
BDD anode
Complete removal
[39• ]
Applying 1.7 A of current intensity during 88 min of treatment time in the presence of 500 mg/L of Na2 SO4 / Ti/PbO2 - working anode and CF working cathode 3-D electro-catalytic reactor
75%
[40]
Removal
[41]
The best operational conditions: current of 1.0 A during 12.45 min using a concentration of 14 mM of NaCl, with CBZ / Nb/BDD or Ti/IrO2 as anodes
Degradation efficiency of 88.70%
[42• ]
Electrochemical system with a Ti/IrO2 anode and a Zr cathode in the presence of NaCl (0.05 µM)
>90%
[43]
Electrolysis time: 60 min; supporting electrolyte solution: 1 g L−1 Na2 SO4 ; current density: 3 mAcm−2 ; electrode spacing of 1 cm / CeO2 /MWCNTs
100%
[44]
Pharmaceutical wastewater
Direct oxidation
Phenacetin
Alkaline media
Carbamazepine
Cephalexin, cephadroxyl, cloxacillin, oxacillin, ciprofloxacin, norfloxacin
Real wastewater from the secondary settler of an activated sludge treatment plant and spiked with CBZ and NaCl Synthetic hospital wastewater and seawater containing one antibiotic
Direct oxidation and indirect oxidation Indirect oxidation by electro-generated active chlorine had the main contribution.
Ceftazidime
Simulated wastewater
The attack of electro-generated active chlorine was found to be the main degradation route. The attack of hydroxyl radicals electro-generated on the surface of the anode
(continued on next page)
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Table 2
Electrochemical conditions/ Electrode
Degradation efficiency (%)
Ref.
Iopromide, sulfamethoxazo-le, 17alpha-ethinylestradiol, diclofenac Ceftazidime
Simulated waste-water and real hospital effluent wastewater
[45• ]
84%
[46• ]
Tetracaine
0.05 M Na2 SO4 , real urban waste-water and a simulated matrix
electrochemical oxidation with electrogenerated H2 O2
> 50% of TOC abatement after 360 min of electrolysis
[47]
Mixture of diclofenac, ibuprofen and naproxen Ketoprofen, diclofenac, ibuprofen, naproxen
Deionized water and WWTP effluent
Electro-Fenton process
The experimental set-up consisted of a flow-through electrochemical cell, a circulation tank and a centrifugal pump / BDD anode Cobalt sulfide/partly-graphitized carbon (Co9 S8 /PGC) composites as cathode Undivided cell with a 3 cm2 BDD, Pt, IrO2 -based or RuO2 -based anode and a 3 cm2 air-diffusion cathode that allowed continuous H2 O2 electrogeneration / BDD, Pt, IrO2 -based or RuO2 -based anode EF with a current density of 40 mA cm−2 and 0.3 mmol Fe2+ L−1
100%
Bio-refractory organic wastewater
The attack of hydroxyl radicals electrogenerated on the surface of the anode. H2 O2 generated from the 2e− oxygen reduction reaction
Up to 90%
[48]
Real wastewater
Bio-electro-Fenton process
Ketoprofen: 59–61%, diclofenac: 87-97%, ibupro- fen:80–86%, naproxen:75–81%
[49• ]
Amoxicillin
Ultrapure water
Close to 100%
[50• ]
Naproxen
Artificial solution
The attack of hydroxyl radicals electrogenerated on the surface of the anode Different EAOPs: EO-H2 O2 , EF, PEF
Optimum parameters: pH=2, Fe2+ =7.5 mM, air-flow=8 mL min−1 , E = 0.3 V / A laboratory scale rectangular bio-electrochemical system consisting of two chambers, based on non-conducting polycarbonate sheets Carbon-felt, carbon fiber, carbon-graphite, platinum, lead dioxide, dimensionally stable anode (DSA), Ti/RuO2–IrO2 and BDD Pt, IrO2-based, RuO2-based and BDD
Total mineralization with BDD in PEF
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Table 2 (continued)
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showed lower removal rate constants than with distilled water matrices [49• ]. The anode material has a strong influence on the selectivity and efficiency of the degradation process, their different behavior being explained by a model that assumes the existence of ‘‘active’’ and ‘‘non-active’’ anodes. Both kinds of anodes (M) oxidize the water forming the physisorbed hydroxyl radical (M(•OH)). This radical interacts strongly with the surface of the ‘‘active’’ anodes, being transformed into the chemisorbed “active oxygen” or superoxide MO, with the MO/M pair being a mediator in the electrochemical conversion of organic compounds; the surface of “non-active oxygen” anodes interact weakly with M(•OH) and this radical directly reacts with organics until total mineralization is achieved. Ruthenium dioxide, iridium dioxide, platinum, graphite and other sp2 carbon-based electrodes are typical examples of “active anodes”, while lead dioxide, tin dioxide, BDD and sub-stoichiometric TiO2 electrodes can be considered as “non-active” electrodes, with the BDD anode being the most potent “non-active” anode known, hence the most suitable anode for AO [31]. This was proved by a study testing the electro-oxidation capacities for the destruction of amoxicillin (AMX) of several electrode materials: carbon-felt, carbon fiber, carbon-graphite, platinum, lead dioxide, dimensionally stable anode (DSA), Ti/RuO2–IrO2 and BDD, with the latter being the best anode material for the large current densities due to generation of high amount of different oxidants, leading to almost complete mineralization of AMX solution. Platinum and carbon felt showed a relatively good oxidation behavior compared to carbon-fiber and carbon-graphite and DSA was found to be the less efficient electrode [50• ].
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Several studies regarding the treatment of wastewaters polluted with pharmaceuticals by the application of different electrochemical procedures are presented in Table 2.
Conclusion and perspectives In this review, we have described the recent works on electrochemical based methods for detection and removal of several drugs classes. While for the detection the conventional separation techniques are still the golden standard, few attempts were reported in the last two years on the electrochemical detection of drugs. An increased interest was observed for the detection of antibiotics and hormones, which presents toxic effect with accumulation in waste waters creating bacteria with high resistance to the commonly used antibiotics or disrupt the hormonal balance. Due to the high oxidation potential of the most classes of antibiotics, the BDD electrode as well as biomimetic elements (aptamers and molecular imprinted polymers based sensors) are intensively used. Nevertheless, the detection procedures are far from being applicable on real samples due to the high amount of organics that are currently found in waste waters and low concentration of drugs. Preconcentration methods or FIA could be envisaged when working on waste waters. Anyway, the things are complicated due to the lack of harmonized legislation regarding the maximum admissible limits of various classes of drugs, the lack of standardized methods for sampling and pretreatment of waste waters from a country to another, the deficiency in electrode materials (only BDD proved to be a suitable material for high oxidation potentials necessary to detect and remove drugs), the necessary improvement of the detection sensitivity and selectivity.
Multi-walled carbon nanotubes (MWCNTs), Pt nanoparticles (Pt NPs), and PtRu alloy were used to synthesize three types of cheap and effective anodes based on commercial conductive glass for the degradation of ibuprofen. Addition of MWCNTs effectively reduced the grain size of electrocatalyst and EAOPs with the anode based on bimetallic PtRu nanoparticles were very effective due to advantages of the higher capacitance, catalytic ability at less positive voltage and stability [51].
Electrochemical methods are also successfully employed as effective technologies for the remediation of waters containing pharmaceutical pollutants. Extensive research has been made in recent years on pharmaceuticals removal from waters by electrochemical conversion an combustion employing strategies such as direct electron transfer, generation of •OH, H2 O2 or active chlorine species, EAOPs based on Fenton’s reaction or using “active” or “non-active” anodes to name a few.
The naproxen degradation was evaluated using different anodes (Pt, IrO2-based, RuO2-based and BDD) and EAOPs. Regardless of the anode, it was obtained this growing oxidation power: electro generated H2 O2 (EOH2 O2 ) < electro-Phenton (EF) < PEF. The IrO2 -based anode led to greater mineralization in EO-H2 O2 and EF, BDD better in PEF (total mineralization). In PEF, the naproxen concentration decay in PEF, it was enhanced in the sequence: RuO2 -based < Pt < BDD < IrO2 -based [52].
Still, electrochemical detection methods have certain advantages over the analytical methods currently used for drugs in waste waters like: low limits of detection, simple instrumentation, in situ analysis, cost of analysis and of electrochemical equipments, and no need for trained personal.
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Acknowledgments This work was supported by a grant of the Romanian National Authority for Scientific Research and Innovation, CNCS/CCCDI-UEFISCDI, project number PN-III-P2-2.1-PED-2016-0172, within PNCDI III. Also, this work was supported by a grant of Ministry of Research and Innovation, CNCS Current Opinion in Electrochemistry 2018, 000:1–11
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Current Opinion in Electrochemistry 2018, 000:1–11
Please cite this article as: Feier et al., Electrochemical detection and removal of pharmaceuticals in waste waters, Current Opinion in Electrochemistry (2018), https://doi.org/10.1016/j.coelec.2018.06.012