Journal of Hazardous Materials 300 (2015) 298–306

Contents lists available at ScienceDirect

Journal of Hazardous Materials journal homepage: www.elsevier.com/locate/jhazmat

Electro-peroxone treatment of the antidepressant venlafaxine: Operational parameters and mechanism Xiang Li, Yujue Wang, Jian Zhao, Huijiao Wang, Bin Wang, Jun Huang, Shubo Deng, Gang Yu ∗ School of Environment, Beijing Key Laboratory for Emerging Organic Contaminants Control, State Key Joint Laboratory of Environmental Simulation and Pollution Control, Tsinghua University, Beijing 100084, China

h i g h l i g h t s

g r a p h i c a l

a b s t r a c t

• E-peroxone is a novel electrocatalytic ozonation process that couples ozonation with electrolysis to enhance pollutant decay. • Carbon-based cathodes are used to electrocatalytically produce H2 O2 from O2 in sparged O2 and O3 mixture. • The in-situ generated H2 O2 reacts • with O3 to yield OH for pollutant mineralization. • Venlafaxine is mineralized much faster by E-peroxone than by ozonation and electrolysis.

a r t i c l e

i n f o

Article history: Received 17 March 2015 Received in revised form 9 June 2015 Accepted 3 July 2015 Available online 6 July 2015 Keywords: Electrocatalysis Venlafaxine Hydrogen peroxide Pharmaceutical Hydroxyl radical

a b s t r a c t Degradation of the antidepressant venlafaxine by a novel electrocatalytic ozonation process, electroperoxone (E-peroxone), was studied. The E-peroxone treatment involves sparging ozone generator effluent (O2 and O3 gas mixture) into an electrolysis reactor that is equipped with a carbonpolytetrafluoroethylene cathode to electrocatalytically transform O2 in the bubbled gas to H2 O2 . The in-situ generate H2 O2 then reacts with the bubbled O3 to yield • OH, which can non-selectively degrade organic compounds rapidly in the solution. Thanks to the significant • OH production, the E-peroxone treatment greatly enhanced both venlafaxine degradation and total organic carbon (TOC) removal as compared to ozonation and electrolysis alone. Under optimal reaction conditions, complete venlafaxine degradation and TOC elimination could be achieved within 3 and 120 min of E-peroxone process, respectively. Based on the by-products (e.g., hydroxylated venlafaxine, phenolics, and carboxylic acids) identified by UPLC–UV and UPLC/Q-TOF-mass spectrometry, plausible reaction pathways were proposed for venlafaxine mineralization by the E-peroxone process. The results of this study suggest that the E-peroxone treatment may provide a promising way to treat venlafaxine contaminated water. © 2015 Published by Elsevier B.V.

∗ Corresponding author at: School of Environment, Tsinghua University, Beijing 100084, China. Fax: +86 10 62785687. E-mail address: [email protected] (G. Yu). http://dx.doi.org/10.1016/j.jhazmat.2015.07.004 0304-3894/© 2015 Published by Elsevier B.V.

X. Li et al. / Journal of Hazardous Materials 300 (2015) 298–306

1. Introduction Venlafaxine (i.e., 1-[2-(dimethyl amino)-1-(4-methoxy-phenyl) ethyl] cyclohexane hydrochloride) is an emerging pharmaceuticals that has aroused increasing concern since it was firstly documented as an environmental contaminant in 2008 [1]. It is a new form of antidepressants and mainly used to regulate the uptake of serotonin, norepinephrine, and dopamine [2]. Due to its effectiveness in curing depression and melancholia, venlafaxine has been increasingly dispensed worldwide. For example, Venlafaxine was the sixth most commonly prescribed antidepressant in U.S. antidepressant retail market (17.2 million in 2007 alone [3]). However, venlafaxine cannot be completely metabolized by human body after ingestion, and is therefore often excreted as unchanged parent compound and major biochemical active metabolites (e.g., o-dimethyl venlafaxine). As a result, venlafaxine and its metabolites have been detected at various concentrations in sewage wastewaters [4–7]. Moreover, because conventional sewage treatment process (e.g., activated sludge) usually cannot effectively degrade venlafaxine and its metabolites [7,8], these compounds can be released with the effluents of wastewater treatment plants (WWTPs) into the water environment [1,4–7,9]. Consequently, venlafaxine and its metabolites have been increasingly detected in various surface water, ground water, and even drinking water [10–12]. Venlafaxine has a high solubility (0.27 g/L) and low Henry coefficient (2.04 × 10−11 atm m−3 mol−1 ) [13]. The volatilization of venlafaxine from aqueous phase is therefore negligible. Moreover, direct photo degradation and biotic degradation of venlafaxine occur at very slow rates in surface water [10]. Therefore, venlafaxine and its metabolites can remain in the aquatic environment for long time, and cause chronic sublethal and acute lethal toxicity to aquatic life [14]. For example, they can affect the central nervous system, disrupt the neuron-endocrine signaling, and alter the reproduction patterns of aquatic organisms [15]. Moreover, it has been reported that at a concentration of 500 ng/L, venlafaxine can produce effects on embryonic development in fathead minnows, affecting their latency period and total escape response [16]. To protect water resources and the ecosystem, water contaminated with venlafaxine needs to be effectively treated. Ozone (O3 ) has been increasingly used as an oxidant to degrade pharmaceuticals and other emerging contaminants in water [17–19]. However, only very few studies have investigated the degradation of venlafaxine by O3 -based processes [4]. Lester et al. [4] reported that ozonation can degrade ∼98% venlafaxine in pharmaceutical wastewater, which however required very high ozone doses (∼152 mg O3 per liter water processed). Moreover, decreasing solution pH from 7 to 5, which minimizes O3 decomposition to • OH (Eq. (1)) [20], resulted in a decline in the degradation rate of venlafaxine because venlafaxine reacts with molecular O3 much slower (kO3 = 3.3 × 104 M−1 s−1 [4]) than with • OH (k• OH = 8.9 × 109 M−1 s−1 [21]). Furthermore, due to the selective oxidation capacity of O3 , ozonation is inefficient at pollutant mineralization, and might generate some toxic transformation products during venlafaxine degradation [4,22]. These previous studies suggest that more effective O3 -based processes than ozonation alone are required to improve the mineralization of venlafaxine and its transformation products, thus minimizing the environmental risks of venlafaxine contaminated water. •

•

−

2O3 + OH− → OH + O2 + 2O2

(1)

To this end, this study tested the degradation of venlafaxine by the electro-peroxone (E-peroxone) process, a novel electrocatalytic ozonation process developed by combining conventional ozonation

299

with electrolysis processes [23]. The E-peroxone process involves sparging an O2 and O3 gas mixture (i.e., ozone generator effluent) into an electrolysis reactor that contains wastewater to be treated. The reactor is equipped with a carbon-polytetrafluoroethylene (carbon-PTFE) cathode that serves as an electrocatalyst to electrochemically convert O2 in the sparged gas to H2 O2 (Eq. (2)). The in-situ generated H2 O2 then reacts with O3 in the sparged gas via the so-called peroxone reaction (Eq. (3)) to produce • OH [23]. In addition, O3 can also be converted to • OH via electroreduction at the cathode (Eq. (4)), and self decomposition under high local pH near the cathode (Eq. (1)) in the E-peroxone process [23]. Because • OH is a non-selective oxidant and has a much higher oxidation ability than O3 , we expected that the E-peroxone process may be able to significantly improve the degradation of venlafaxine and its transformation products as compared to ozonation alone. Effects of key operational conditions (e.g., applied current, O3 , electrolytes, and pH) were evaluated systematically. Intermediates formed from venlafaxine degradation were identified by UPLC–UV and UPLC/Q-TOF-mass spectrometry to figure out the degradation pathway of venlafaxine during the E-peroxone process. O2 + 2H+ + 2e− → H2 O2

(2)

•

H2 O2 + 2O3 → 2 OH + 3O2 •

(3) −

O3 + H2 O + e− → OH + O2 + OH

(4)

2. Materials and methods 2.1. Reagent and chemicals Venlafaxine, hydroquinone, and catechol were obtained from Dr. Ehrenstorfer GmbH. Carboxylic acids (oxalic, lactic, pyruvic, and maleic acids) were purchased from Fluka. Formic acid was from the company of Dikma in the USA. Other chemicals were obtained from Modern Eastern Fine Chemical in China. Ultrapure water was obtained from a Milli-Q machine (Milli-pore, USA). Secondary effluent samples were collected from a WWTP located in the northwest of Beijing in China. The secondary effluent had a pH of ∼7.1, 8.14 mg/L natural organic matter (NOM), and 65.34 mg/L carbonate content. 2.2. Degradation of venlafaxine by ozonation, electrolysis, and the E-peroxone process Experiments were carried out in an undivided 500 mL acrylic reactor. The initial concentration of venlafaxine in the solution was 20 mg/L. For ozonation process, O3 was produced from pure O2 gas (99.9%) using an ozone generator (OL80F/DST, Ozone services, Canada). The concentrations of O3 in the ozone generator effluent (O2 and O3 gas mixture) could be adjusted by changing the ozone generator power, and were monitored using an ozone monitor (BMT 964, Germany). The ozone generator effluent was sparged into the bottom of the reactor at a constant flow rate of 0.25 L/min. E-peroxone and electrolysis processes were conducted under galvanostatic conditions using a DC power supply. The reactor cell contains a Pt plate anode (2 cm2 ) and a carbon-PTFE cathode (20 cm2 ). The carbon-PTFE electrodes were prepared with carbon powder, PTFE solution and anhydrous alcohol using the procedure described previously [24]. The distance between the anode and cathode was 1 cm, and the electrolyte was 0.05 M Na2 SO4 solution unless otherwise specified. All experiments (ozonation, electrolysis, and E-peroxone) were conducted in triplicate for 120 min, during which the reactor was placed in a water bath to keep the temperature at 25 ± 2 ◦ C. Magnetic stirring

300

X. Li et al. / Journal of Hazardous Materials 300 (2015) 298–306

Fig. 1. Venlafaxine degradation in (a) background electrolyte and (b) secondary effluent by ozonation, electrolysis, and E-peroxone process (initial concentration of venlafaxine = 20 mg/L; volume = 300 mL; initial pH 7.9 (uncontrolled); inlet O3 gas phase concentration = 20 mg/L; sparging gas flow rate = 250 L/min; current = 200 mA).

was applied to thoroughly mix the venlafaxine solution during the treatments.

3. Results and discussion 3.1. Degradation of venlafaxine by ozonation, electrolysis, and E-peroxone processes

2.3. Analytical methods During the treatment, aqueous samples were collected from the reactor at an array of reaction times for analysis. The concentrations of dissolved ozone during the E-peroxone process were determined with indigo method [25]. The concentrations of H2 O2 were determined using potassium titanium (IV) oxalate method [26]. Total organic carbon (TOC) was measured using a TOC-VCPH analyzer (Shimadzu Co, Japan). Venlafaxine, phenolic intermediates, carboxylic acid intermediates were quantified using a ultra-high-performance liquid chromatography (UPLC) coupled with a UV detector. The oven temperature was set at 30 ◦ C and the flow rate was 1.0 mL/min. For venlafaxine analysis, a reversed-phase TC-C18 column (5 ␮m, 150 mm × 4.6 mm, Agilent, USA) was used and the detection wavelength was 226 nm. The mobile phase was 60% methanol and 40% water. The pH was adjusted using 2 mM CH3 COONH4 and 0.1% formic acid. For the analysis of phenolic intermediates (hydroquinone, and catechol), the column was ZORBAX SB-C18 (5 ␮m, 4.6 × 150 mm, Agilent) and the detection wavelength was 280 nm. The mobile phase was 50% methanol and 50% water. For carboxylic acid intermediates, the column was an Atlantics columns T (3.5 ␮m, 4.6 × 150 mm, Waters) and the mobile phase was 20 mM NaH2 PO4 water solution whose pH was adjusted to 2.6 with phosphoric acid. The UV detector was operated at 210 nm. The other aromatic by-products were identified using a UPLC (Ultimate 3200, Dionex) equipped with a quadrupole time-of-flight mass spectrometer (Q-TOF-MS, micro-TOF-Q III, Bruker, Germany) [27]. Due to the high detection limit, samples need to be concentrated before ESI-TOF-MS analysis. 500 mL solution sample was introduced into an Oasis HLB cartridge (Waters, USA) at a flow rate of 3–5 mL/min. After the solid phase extraction, the cartridge was eluted by 15 mL methanol. Then the extract was concentrated to 0.5 mL under a gentle stream of nitrogen in a water bath at 30–35 ◦ C. Separation was performed with a reversed-phase SB-Aq column (3.5 ␮m, 150 mm × 3 mm, Agilent). The mobile phase was a mixture of 0.1% (volume) formic acid in water (A) and methanol (B) at a flow rate of 0.4 mL/min. The elution started with 2% of B for 2 min, and then increased linearly to 90% of B in 20 min, which was maintained for another 5 min. The Q-TOF-MS was operated in positive electrospray ionization mode for intermediates identification.

Degradation of venlafaxine in the background electrolyte (0.05 M Na2 SO4 ) by ozonation, electrolysis, and the E-peroxone process were compared in Fig. 1(a). As shown, the E-peroxone process degraded venlafaxine much more rapidly than the individual ozonation and electrolysis process. Kinetic analysis indicates that venlafaxine degradation can be generally described by pseudofirst-order kinetics for all three processes (see Table 1). Notably, the E-peroxone process significantly enhanced the apparent degradation rate constant of venlafaxine (kapp = 22.5 × 10−3 s−1 ) compared with the individual treatment process of ozonation (kapp = 8.1 × 10−3 s−1 ) and electrolysis (kapp = 0.48 × 10−3 s−1 ). This result is consistent with the previous finding that the combination of ozonation with electrolysis can greatly enhance the pollutant degradation kinetics because significant amounts of • OH can be produced during this process, e.g., from the electrochemicallydriven peroxone reaction (Eq. (3)), O3 electro-reduction at the cathode (Eq. (4)), and O3 decomposition at high local pH near the cathode (Eq. (1)) [28–30]. The degradation of venlafaxine in real wastewater was also investigated for the three processes (see Fig. 1(b)). A known amount of venlafaxine was spiked into secondary effluent samples collected from a WWTP in Beijing, and then treated by ozonation, electrolysis, and E-peroxone processes. The secondary effluent had lower initial pH (∼7.1), but considerably higher contents of NOM (DOC = 8.14 mg/L) and carbonates (alkalinity = 65.34 mg/L) than the background electrolyte tested previously (pH 7.9, DOC = 0 mg/L, alkalinity = 0 mg/L). Many studies have indicated that water quality parameters (especially pH, NOM, and carbonates) can considerably influence the degradation of target pollutants in O3 -related processes [31,32]. For example, depending on its nature and reaction conditions, NOM can initiate, propagate, and terminate the radicals reactions of O3 , and thus have complicated effects on pollutant degradation in O3 -based processes [33–35]. On the other hand, carbonates mainly act as • OH scavenger, thus decreasing the efficiency of • OH-driven AOPs[36]. Interestingly, a comparison between Fig. 1(a) and (b) shows that for a given process (i.e., ozonation, electrolysis, or E-peroxone), venlafaxine degradation rates in the background electrolyte and secondary effluentare generally comparable.This similarity suggests that the individual effects of water quality parameters (e.g., pH, NOM, and carbonates) of the second effluent on venlafaxine

X. Li et al. / Journal of Hazardous Materials 300 (2015) 298–306

301

Table 1 Pseudo-first-order rate constant and square coefficient for the degradation of venlafaxine under different reaction conditions. Run.

Process

C0 (mg/L)

Initial pH

I (mA)

O3 (mg/L)

Electrolyte

Kapp (10–3 s–1 )

r2

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20

Electrolysis Electrolysisa Ozonation Ozonationa E-peroxone E-peroxonea E-peroxone E-peroxone E-peroxone E-peroxone E-peroxone E-peroxone E-peroxone E-peroxone E-peroxone E-peroxone E-peroxone E-peroxone E-peroxone E-peroxone

20 20 20 20 20 20 20 20 20 20 20 20 20 20 20 20 20 20 20 20

7.9 7.1 7.9 7.1 7.9 7.1 7.9 7.9 7.9 7.9 7.9 7.9 7.9 7.9 7.9 7.9 7.9 3.5 (fixed) 7.5 (fixed) 10.5 (fixed)

200 200 0 0 200 200 200 200 200 200 50 150 300 450 200 200 200 200 200 200

0 0 20 20 20 20 6.5 18 30 42 40 40 40 40 20 20 20 20 20 20

Na2 SO4 Na2 SO4 Na2 SO4 Na2 SO4 Na2 SO4 Na2 SO4 Na2 SO4 Na2 SO4 Na2 SO4 Na2 SO4 Na2 SO4 Na2 SO4 Na2 SO4 Na2 SO4 Na2 SO4 NaCl NaClO4 Na2 SO4 Na2 SO4 Na2 SO4

0.48 0.33 8.1 9.9 22.5 20.4 9.6 21.9 25.6 39.7 19.4 38.5 53.2 48.1 24.9 14 10.5 19.8 36.5 81.7

0.74 0.78 0.93 0.82 0.87 0.83 0.99 0.96 0.99 0.98 0.99 0.99 0.99 0.99 0.98 0.95 0.95 0.97 0.89 0.94

a

Experiment conducted with secondary effluent samples collected from a wastewater treatment plant.

degradation were balanced in the treatment. For example, it was found that venlafaxine was degraded at a slightly higher rate in the secondary effluent (kapp = 9.9 × 10−3 s−1 ) than in the background electrolytes (kapp = 8.1 × 10−3 s−1 ) by ozonation alone (see Table 1). This is possibly because some NOM in the secondary effluent may enhance O3 transformation to • OH [28,30], thus enhancing venlafaxine degradation. On the other hand, NOM and carbonates can also consume • OH, and thus decrease the rate of venlafaxine degradation in the secondary effluent than in the background electrolyte during the E-peroxone process, in which • OH is mainly generated from the electrochemically driven peroxone reaction (Eq. (2)). Additionally, the different pseudo-first order rate constants could also be due to the structure of venlafaxine and NOM. These organic compounds may contain structure elements that react in a different degree with ozone, for example, they may contain different amounts of functional groups with a lone valence electron pair [34,35]. As described previously, transformation products generated during venlafaxine degradation may also pose potential risks to the environment [14,22,37]. It is therefore desirable to improve the mineralization efficiency of both venlafaxine and its degradation intermediates. Fig. 2 shows that the E-peroxone process degraded TOC more rapidly than ozonation alone and electrolysis alone. This result indicates that E-peroxone is a superior process to mineralize venlafaxine and its transformation products than the two individual processes. This enhancement can be explained by the significant production of aqueous • OH from multiple sources during the E-peroxone process [23,28–30], which enables non-selective mineralization of venlafaxine and its transformation products from the solution. In comparison, pollutant mineralization kinetics is limited by the selective oxidation of O3 in ozonation process, and mass transfer of pollutants to the anode in electrolysis process [31,38,39]. Consequently, ozonation is usually ineffective at pollutant mineralization, whereas electrolysis requires long reaction time to achieve high TOC abatement[30,31,39]. 3.2. Effects of operational parameters on venlafaxine degradation by the E-peroxone process Fig. 3 shows that venlafaxine degradation and TOC mineralization efficiency increased with the current (from 50 mA to 300 mA). However, further increasing the current to 450 mA did not enhance venlafaxine degradation and TOC mineralization accordingly (Run

Fig. 2. TOC mineralization by ozonation, electrolysis, and E-peroxone process (initial concentration of venlafaxine = 20 mg/L; volume = 300 mL; initial pH 7.9 (uncontrolled); inlet O3 gas phase concentration = 20 mg/L; sparging gas flow rate = 250 L/min; current = 200 mA).

13 and 14, see Table 1). Similar results have been observed in the previous studies treating synthetic dye and pharmaceutical wastewater [31,38]. As shown in Fig. 3 inset, increasing the applied current increased the rate of H2 O2 electro-generation from O2 at the carbon-PTFE cathode; note that the H2 O2 production test was conducted in the background electrolyte solution (0.05 M Na2 SO4 ) by sparging pure O2 gas during electrolysis [38]. Presumably, as H2 O2 is produced more rapidly at higher applied currents, more • OH can be generated from the subsequent reaction of the electro-generated H2 O2 with the sparged ozone in the E-peroxone treatment. However, due to the low solubility of O3 , • OH production rate would eventually be limited by the rate of O3 transfer from gas phase to liquid phase as the current is increased beyond a critical value (e.g., 300 mA in this study)[31,38]. To further verify this inference, we monitored aqueous O3 and H2 O2 concentrations during the E-peroxone treatment of venlafaxine operated at the different applied currents (50–450 mA). As shown in the Supplementary Data (SD) Fig. S1, with the increase in the applied current, the pseudo-steady concentrations of H2 O2 increased progressively, while the O3 concentrations decreased. This trend indicates that as the applied current is increased, H2 O2

302

X. Li et al. / Journal of Hazardous Materials 300 (2015) 298–306

Fig. 3. Effects of applied current on (a) venlafaxine degradation and (b) TOC mineralization in the E-peroxone process (initial concentration of venlafaxine = 20 mg/L; volume = 300 mL; initial pH 7.9 (uncontrolled); sparging gas flow rate = 250 L/min; inlet O3 gas phase concentration = 40 mg/L).

is more rapidly generated in the system, which leads to more rapid consumption of aqueous O3 via the peroxone reaction. Notably, as the current was increased from 300 to 450 mA, H2 O2 concentration increased dramatically from ∼0.37 to > 0.94 mM, while O3 concentration decreased from ∼0.19 to ∼0.03 mM. These sudden changes indicate that at 450 mA, aqueous O3 consumed in its reaction with electro-generated H2 O2 could not be adequately replenished by the O3 transferred from the sparged gas into the liquid. This result confirms the previous inference that when the E-peroxone was operated at 450 mA, • OH production via the reaction of sparged O3 and electro-generated H2 O2 is limited by the mass transfer of O3 from the gas phase to the liquid phase. As a result, the concentrations of aqueous O3 decreased to very low level, while H2 O2 accumulated in significant amounts in the solution. When there is insufficient aqueous O3 to react with the electro-generated H2 O2 , the excess H2 O2 contributes little to TOC mineralization because it is not a powerful oxidant. Moreover, the excess H2 O2 can act as a • OH scavenger, thus terminating the radical chain reactions that lead to pollutant mineralization in AOPs [36]. This may explain why increasing the current beyond 300 mA did not further increase the rate of venlafaxine degradation and TOC mineralization. Fig. 4 shows that increasing O3 concentration in the sparged gas enhanced both venlafaxine degradation and TOC mineralization. This result is consistent with the finding of previous E-peroxone studies [23,28,38], and can be attributed to the fact that increasing the gas phase O3 concentration enhances O3 mass transfer rate to the aqueous phase. Consequently, more • OH can be generated from reactions such as (Eq. (2–4) to rapidly degrade pollutants in the solution [30].

The above experiments were carried out without controlling the solution pH, which decreased from ∼7.9 to ∼3.8 within the first 60 min, and then increased to ∼6.7 at the end of E-peroxone treatment (see Fig. 2 inset). This change can be mainly attributed to the formation and subsequent removal of carboxylic acid intermediates during the degradation of venlafaxine by the E-peroxone treatment (see discussion below and refer to [29,39]). To evaluate the effects of solution pH on the degradation of venlafaxine and TOC, the solution pH was controlled at three constant values (3.5, 7.5 and 10.5) throughout the whole reaction time by adding small amounts of 0.05 M NaOH or H2 SO4 . Fig. 5 shows that the rate of venlafaxine degradation increased as the solution pH was increased from 3.5 to 10.5. However, the rate of TOC decay increased in different order of pH 3.5, pH 10.5, and pH 7.5. This result indicates that solution pH has complex effects on venlafaxine degradation and TOC removal during the E-peroxone process. Because venlafaxine has a tertiary amine with pKa of 9.24 [9], it exists primarily in the non-protonated form at pH 10.5, and protonated form between pH 7.5 and 3.5. It is well-known that non-protonated amines react with O3 many orders of magnitude faster than their protonated forms [33]. This may account for the faster degradation of venlafaxine at higher solution pH (Fig. 5(a)). Regarding TOC removal, our previous studies on E-peroxone treatment of synthetic dye wastewater have suggested that the mineralization efficiency of E-peroxone process may decrease with increasing solution pH [31,38]. This is mainly because increasing solution pH enhances O3 transformation to HO2 – (the conjugated base of H2 O2 ) (Eq. (5)). As a result, the molar ratio of O3 to H2 O2 /HO2 – may decrease below the optimal ratio (usually 1–2) for

Fig. 4. Effects of O3 concentration in the sparged gas on (a) venlafaxine degradation and (b) TOC mineralization in the E-peroxone process (initial concentration of venlafaxine = 20 mg/L; volume = 300 mL; initial pH 7.9 (uncontrolled); sparging gas flow rate = 250 L/min; current = 200 mA).

X. Li et al. / Journal of Hazardous Materials 300 (2015) 298–306

303

Fig. 5. Effects of solution pH on (a) venlafaxine degradation and (b) TOC mineralization in the E-peroxone process (initial concentration of venlafaxine = 20 mg/L; volume = 300 mL; sparging gas flow rate = 250 L/min; current = 200 mA. inlet O3 gas phase concentration = 20 mg/L.

peroxone process when sufficient H2 O2 /HO2 – is electrochemically generated from O2 at the carbon cathode (e.g., 300 mA in this study, see discussion of Fig. 3) [28,31,38]. When H2 O2 /HO2 – becomes in excess relative to aqueous O3 , they can actually scavenge • OH (Eq. (6)), thus impeding pollutant mineralization [31,38]. That may explain that the TOC mineralization efficiency decreased when the solution pH was controlled at 10.5 compared to the neutral pH (Fig. 5(b)). On the other hand, decreasing the solution pH from 7.5 to 3.5 results in the protonation of many carboxylic acids (e.g., oxalic and formic acid) that are major intermediates formed during venlafaxine degradation (see discussion below). Because protonated carboxylic acids react with • OH usually much slower than their deprotonated species (e.g., the rate constants for reaction of • OH with oxalic acid (H2 C2 O4 ) and bioxalate (HC2 O4 – ) are 1.4 × 106 M−1 s−1 and 4.7 × 107 M−1 s−1 , respectively [40]), TOC removal efficiency of venlafaxine from acidic solution (pH 3.5) was lower than that of nearly neutral solution (pH 7.5). O3 + OH− → HO2 − + O2 −

◦

HO2 + OH →

• O H + OH− 2

ated from O2 more rapidly in Na2 SO4 than in NaCl. It has therefore been inferred that the rate of TOC removal is related to that of H2 O2 electro-generation during the E-peroxone treatment[38]. Consistently, Fig. 6(a) inset shows that as the oxygen is sparged into the different electrolytes, the rate of H2 O2 electro-generation increased in order of NaClO4 , NaCl, and Na2 SO4 , which is in the same order of venlafaxine degradation and TOC mineralization in the E-peroxone process (Fig. 6(a) and (b)). This trend is possibly because the NaCl and NaClO4 electrolytes had a lower electrical conductivity than the Na2 SO4 electrolyte. As a result, the average cell voltage increased from ∼10.5 V for Na2 SO4 to ∼19.8 V for NaCl and ∼22.4 V for NaClO4 . The increase of cell voltage may result in more side reactions such as H2 evolution at the carbon-PTFE cathode, and therefore decrease the rates of H2 O2 electro-generation at the cathode and ensuing • OH production in the solution. Consequently, venlafaxine degradation and TOC mineralization occurred more rapidly in the Na2 SO4 electrolyte than in the NaCl and NaClO4 electrolytes.

(5) (6)

To evaluate the effects of background electrolytes on venlafaxine degradation and TOC abatement, the E-peroxone treatment was conducted in different electrolytes (0.05 M Na2 SO4 , NaCl, and NaClO4 solutions). As shown in Fig. 6, the rates of both venlafaxine degradation and TOC abatement increased in order of NaClO4 , NaCl, and Na2 SO4 . This trend agrees with the previous finding that E-peroxone is more effective at pollutant degradation when it is operated in Na2 SO4 electrolytes than in NaCl electrolytes [38]. In the previous study, we found that H2 O2 is electrochemically gener-

3.3. Intermediates identification and suggested degradation pathways Intermediates formed during E-peroxone degradation of venlafaxine were concentrated via solid phase extraction, and then analyzed using UPLC/Q-TOF-MS. The pre-concentration and high resolving power endorsed by TOF instruments allow us to detect intermediates formed at low concentrations. The elemental compositions and molecular structures of intermediates were then proposed based on their accurate mass measurement of ion fragments (see Table 2). In addition, a variety of phenolic and carboxylic

Fig. 6. Effects of electrolyte on (a) venlafaxine degradation and (b) TOC mineralization in the E-peroxone process (initial concentration of venlafaxine = 20 mg/L; volume = 300 mL; sparging gas flow rate = 250 L/min; current = 200 mA. inlet O3 gas phase concentration = 20 mg/L).

304

X. Li et al. / Journal of Hazardous Materials 300 (2015) 298–306

Table 2 Intermediates identified during E-peroxone degradation of venlafaxine. No

Name

Formula [M]

[M+H]a

tR (min)

Method

1 2 3

1-(2-(dimethylamino)-1-(4-methoxyphenyl)ethyl)cyclohexane 4-(2-(dimethylamino)-1-(1-hydroxycyclohexyl)ethyl)phenol Mono hydroxylated venlafaxine (isomer a) Mono hydroxylated venlafaxine (isomer b) Mono hydroxylated venlafaxine (isomer c) Mono hydroxylated venlafaxine (isomer d) Trihydroxylated venlafaxine Dihydroxylated venlafaxine 4-(2-(dimethylamino)-2-hydroxy-1-(1-hydroxycyclohexyl)ethyl)phenol 4-(2-(dimethylamino)-2-hydroxy-1-(1-hydroxycyclohexyl)ethyl) benzene-1,2-diol (isomer a) 4-(2-(dimethylamino)-2-hydroxy-1-(1-hydroxycyclohexyl)ethyl) benzene-1,2-diol (isomer b) 2-(cyclohex-1-en-1-yl)-N,N-dimethyl-2-(2,3,4,5-tetrahydroxyphenyl)acetamide 4-(2-hydroxy-1-(1-hydroxycyclohexyl)-2-(methylamino)ethyl)benzene-1,2-diol 4-(2-amino-2-hydroxy-1-(1-hydroxycyclohexyl)ethyl)benzene-1,2-diol 4-(2-hydroxy-1-(1-hydroxycyclohexyl)ethyl)benzene-1,2-diol 5-(2-(dimethylamino)-2-hydroxyethyl)-2-methoxyphenol Catechol Hydroquinone Oxalic acid Lactic acid Pyruvic acid Malic acid

C17 H27 NO2 C16 H25 NO2 C17 H27 NO3 C17 H27 NO3 C17 H27 NO3 C17 H27 NO3 C17 H27 NO5 C17 H27 NO4 C16 H25 NO3 C16 H25 NO4

278.1762 264.1961 294.2064 294.2064 294.2064 294.2064 326.1961 310.1968 280.1829 296.1855

13.5 11.8 9.4 11.8 12.4 14.2 2.1 11.3 11.1 10.5

UPLC/Q-TOF-MS UPLC/Q-TOF-MS UPLC/Q-TOF-MS UPLC/Q-TOF-MS UPLC/Q-TOF-MS UPLC/Q-TOF-MS UPLC/Q-TOF-MS UPLC/Q-TOF-MS UPLC/Q-TOF-MS UPLC/Q-TOF-MS

C16 H25 NO4

296.1855

2.4

UPLC/Q-TOF-MS

C16 H21 NO5 C15 H23 NO4 C14 H21 NO4 C14 H20 O4 C11 H17 NO3 C6 H6 O2 C6 H6 O2 C2 H6 O6 C3 H6 O3 C3 H4 O3 C4 H6 O5

308.1474 282.1687 268.1529 253.1454 212.1276

9.1 10.1 7.9 10 9.6 2.34 1.9 1.98 3.68 2.59 2.98

UPLC/Q-TOF-MS UPLC/Q-TOF-MS UPLC/Q-TOF-MS UPLC/Q-TOF-MS UPLC/Q-TOF-MS HPLC-UV HPLC-UV HPLC-UV HPLC-UV HPLC-UV HPLC-UV

4 5 6 7

8 9 10 11 12 13 14 15 16 17 18 a

Mass of main ion fragments measured by UPLC/Q-TOF-MS.

intermediates was identified and quantified using HPLC-UV. As reported in Table 2, a total of 18 (not including some isomers) intermediates were identified in the solution during venlafaxine degradation by the E-peroxone process. Some of these intermediates (e.g., No.1, 3 and 5 in Table 2) have been reported in previous studies on venlafaxine degradation by ozonation and gamma radiolysis [4,21], whereas many (e.g., some isomers of No. 2 and No. 6, 7 in Table 2) are reported for the first time as the degradation intermediates of venlafaxine. It is noted that most intermediates listed in Table 2 (e.g., No. 2–12) were detected only at the early stage of the E-peroxone treatment of venlafaxine (e.g., within the first 15 min). On the other hand, phenolic and especially carboxylic intermediates existed in the solution for longer reaction time. As shown in Fig. 7, the concentrations of simple phenols (e.g. hydroquinone and catechol) reached a maximum within 5–15 min, and then decreased with reaction time, whereas carboxylic acids such as oxalic acid and lactic acid persisted in the solution until the end of E-peroxone treatment (120 min, see Fig. 7(b)). In fact, carboxylic acids were the predominant organic species at the late stage of E-peroxone treatment, accounting for more than 80% of the solution TOC after 1 h of

the E-peroxone treatment of venlafaxine. These trends are in line with the general observation of many AOP studies that phenols are often the final aromatic intermediates before the rupture of benzene rings that leads to the formation of various linear carboxylic acids, and saturated carboxylic acids such as oxalic acid usually constitute the major end by-products before complete mineralization to CO2 . As reported in Table 2, many hydroxylated intermediates (e.g., mono-, di-, and trihydroxylated venlafaxine) were detected during venlafaxine degradation by the E-peroxone process. This result confirms the important role of • OH in pollutant degradation by Eperoxone process [28,31,38], and agrees with the previous finding of Santoke et al. [22] that • OH can attack various positions of venlafaxine to yield a variety of hydroxylated intermediates. Further • OH attacks of the hydroxylated venlafaxine result in reactions such as demethylation, H-abstraction, and C N bond cleavage, leading to the formation of phenols (e.g., hydroquinone and catechol) and carboxylic acids (e.g., maleic acid, pyruvic acid, and oxalic acid). Finally, similar in most AOPs, saturated carboxylic acids (e.g., oxalic acid) constituted the end by-products before complete mineralization during the E-peroxone treatment (see Fig. 7). Because saturated

Fig. 7. Time-course of the concentrations of (a) phenolic intermediates and (b) carboxylic acid intermediates during the E-peroxone treatment of venlafaxine solution (initial concentration of venlafaxine = 20 mg/L; volume = 300 mL; initial pH 7.9 (uncontrolled); inlet O3 gas phase concentration = 20 mg/L; sparging gas flow rate = 250 L/min; current = 200 mA)

X. Li et al. / Journal of Hazardous Materials 300 (2015) 298–306

305

Fig. 8. Proposed reaction pathways for mineralization of venlafaxine by the E-peroxone process.

carboxylic acids are essentially unreactive with molecular O3 , their mineralization can be mainly attributed to oxidation by • OH generated in the E-peroxone process [23,38]. Parenthetically, venlafaxine contains ∼5.1 wt.% N in its tertiary amine group. At the end of E-peroxone treatment, nitrate was found to be the predominant Nspecies in the solution, accounting for ∼95% of the initial N content (molar ratio) contained in venlafaxine. This result indicates that the amine group of venlafaxine is almost completely converted to nitrate at the end of the E-peroxone treatment. Based on the above information, a plausible reaction scheme for E-peroxone degradation of venlafaxine is proposed in Fig. 8. Due to the complexity of the reaction mechanisms and large number of intermediates, only global reaction steps that lead to total

mineralization are shown herein, for example, (a) hydroxylation of venlafaxine, (b) side chain cleavage of hydroxylated venlafaxine to yield phenols, (c) ring-opening of phenols to carboxylic acids, and (d) final mineralization of carboxylic acids to CO2 . 4. Conclusions The study demonstrates that the E-peroxone treatment is a convenient and effective electrocatalytic ozonation technology to decay venlafaxine within aqueous media. The E-peroxone treatment simply combined the conventional ozonation and the electrolysis together to electrocatalytically transform sparged O2 to H2 O2 , the E-peroxone treatment can electrochemically drive the

306

X. Li et al. / Journal of Hazardous Materials 300 (2015) 298–306

peroxone reaction to produce • OH in bulk solution. As a result, the E-peroxone process greatly enhanced both venlafaxine degradation and TOC mineralization as compared to ozonation alone. The degradation kinetics of venlafaxine followed pseudo-first-order reaction in the E-peroxone treatment, and increased generally with applied current and O3 dosage. Complete mineralization of venlafaxine and its transformation products can be achieved within the E-peroxone treatment, which minimizes the potential environmental risk of E-peroxone effluents. The results suggest that the E-peroxone treatment may offer a promising alternative to treat water contaminated with pharmaceuticals. Acknowledgment This work was supported by the National High Technology Research and Development of China (No. 2013AA06A305), Program for Changjiang Scholars and Innovative Research Team in University, China Postdoctoral Science Foundation (2013T60128), and the special fund of State Key Joint Laboratory of Environment Simulation and Pollution Control (13Y01ESPCT). Appendix A. Supplementary data Supplementary data associated with this article can be found, in the online version, at http://dx.doi.org/10.1016/j.jhazmat.2015.07. 004 References [1] M.M. Schultzt, E.T. Furlong, Trace analysis of antidepressant pharmaceuticals and their select degradates in aquatic matrixes by LC/ESI/MS/MS, Anal. Chem. 80 (2008) 1756–1762. [2] M. Tzanakaki, M. Guazzelli, I. Nimatoudis, N.P. Zissis, Increased remission rates with venlafaxine compared with fluoxetine in hospitalized patients with major depression and melancholia, Int. Clin. Psychopharmacol. 15 (2000) 29–34. [3] S.P. Chavan, S. Garai, K.P. Pawar, Asymmetric total synthesis of (−)-venlafaxine using an organocatalyst, Tetrahedron Lett. 54 (2013) 2137–2139. [4] Y. Lester, H. Mamane, I. Zucker, D. Avisar, Treating wastewater from a pharmaceutical formulation facility by biological process and ozone, Water Res. 47 (2013) 4349–4356. [5] M.O. Uslu, S. Jasim, A. Arvai, J. Bewtra, N. Biswas, A survey of occurrence and risk assessment of pharmaceutical substances in the great lakes basin, Ozone Sci. Eng. 35 (2013) 249–262. [6] A. Lajeunesse, M. Blais, B. Barbeau, S. Sauve, C. Gagnon, Ozone oxidation of antidepressants in wastewater-treatment evaluation and characterization of new by-products by LC-QToFMS, Chem. Cent. J. 7 (2013). [7] C.D. Metcalfe, S. Chu, C. Judt, H. Li, K.D. Oakes, M.R. Servos, D.M. Andrews, Antidepressants and their metabolites in municipal wastewater, and downstream exposure in an urban watershed, Environ. Toxicol. Chem. 29 (2010) 79–89. [8] J. Margot, C. Kienle, A. Magnet, M. Weil, L. Rossi, L.F. de Alencastro, C. Abegglen, D. Thonney, N. Chèvre, M. Schärer, D.A. Barry, Treatment of micropollutants in municipal wastewater: ozone or powdered activated carbon? Sci. Total Environ. 461–462 (2013) 480–498. [9] A. Lajeunesse, C. Gagnon, S. Sauve, Determination of basic antidepressants and their N-desmethyl metabolites in raw sewage and wastewater using solid-phase extraction and liquid chromatography – Tandem mass spectrometry, Anal. Chem. 80 (2008) 5325–5333. [10] P.C. Rúa-Gómez, W. Püttmann, Degradation of lidocaine, tramadol, venlafaxine and the metabolites O-desmethyltramadol and O-desmethylvenlafaxine in surface waters, Chemosphere 90 (2013) 1952–1959. [11] J. Gelsleichter, N.J. Szabo, Uptake of human pharmaceuticals in bull sharks (Carcharhinus leucas) inhabiting a wastewater-impacted river, Sci. Total Environ. 456–457 (2013) 196–201. [12] P.C. Rúa-Gómez, W. Püttmann, Impact of wastewater treatment plant discharge of lidocaine, tramadol, venlafaxine and their metabolites on the quality of surface waters and groundwater, J. Environ. Monit. 14 (2012) 1391–1399. [13] P.C. Rua-Gomez, W. Puettmann, Occurrence and removal of lidocaine, tramadol, venlafaxine, and their metabolites in German wastewater treatment plants, Environ. Sci. Pollut. Res. 19 (2012) 689–699.

[14] R. Feito, Y. Valcárcel, M. Catalá, Preliminary data suggest that venlafaxine environmental concentrations could be toxic to plants, Chemosphere 90 (2013) 2065–2069. [15] B.W. Brooks, P.K. Turner, J.K. Stanley, J.J. Weston, E.A. Glidewell, C.M. Foran, M. Slattery, T.W. La Point, D.B. Huggett, Waterborne and sediment toxicity of fluoxetine to select organisms, Chemosphere 52 (2003) 135–142. [16] M.M. Painter, M.A. Buerkley, M.L. Julius, A.M. Vajda, D.O. Norris, L.B. Barber, E.T. Furlong, M.M. Schultz, H.L. Schoenfuss, Antidepressants at environmentally relevant concentrations affect predator avoidance behavior of larval fathead minnows (pimephales promelas), Environ. Toxicol. Chem. 28 (2009) 2677–2684. [17] R. Rosal, A. Rodriguez, J.A. Perdigon-Melon, A. Petre, E. Garcia-Calvo, M.J. Gomez, A. Aguera, A.R. Fernandez-Alba, Occurrence of emerging pollutants in urban wastewater and their removal through biological treatment followed by ozonation, Water Res. 44 (2010) 578–588. [18] M.M. Huber, S. Canonica, G.Y. Park, U. Von Gunten, Oxidation of pharmaceuticals during ozonation and advanced oxidation processes, Environ. Sci. Technol. 37 (2003) 1016–1024. [19] Y. Lee, D. Gerrity, M. Lee, A.E. Bogeat, E. Salhi, S. Gamage, R.A. Trenholm, E.C. Wert, S.A. Snyder, U. von Gunten, Prediction of micropollutant elimination during ozonation of municipal wastewater effluents: use of kinetic and water specific information, Environ. Sci. Technol. 47 (2013) 5872–5881. [20] R.E. Buhler, J. Staehelin, J. Hoigne, Ozone decomposition in water studied by pulse radiolysis.1. HO2 /O2 − and HO3 /O3 − as intermediates, J. Phys. Chem. 88 (1984) 2560–2564. [21] B.A. Wols, C.H.M. Hofman-Caris, D.J.H. Harmsen, E.F. Beerendonk, Degradation of 40 selected pharmaceuticals by UV/H2O2, Water Res. 47 (2013) 5876–5888. [22] H. Santoke, W. Song, W.J. Cooper, B.M. Peake, Advanced oxidation treatment and photochemical fate of selected antidepressant pharmaceuticals in solutions of Suwannee river humic acid, J. Hazard. Mater. 217–218 (2012) 382–390. [23] S. Yuan, Z.X. Li, Y.J. Wang, Effective degradation of methylene blue by a novel electrochemically driven process, Electrochem. Commun. 29 (2013) 48–51. [24] Y. Wang, X. Li, L. Zhen, H. Zhang, Y. Zhang, C. Wang, Electro-Fenton treatment of concentrates generated in nanofiltration of biologically pretreated landfill leachate, J. Hazard. Mater. 229–230 (2012) 115–121. [25] H. Bader, J. Hoigne, Determination of ozone in water by the indigo method, Water Res. 15 (1981) 449–456. [26] R.M. Sellers, Spectrophotometric determination of hydrogen-peroxide using potassium titanium(IV) oxalate, Analyst 105 (1980) 950–954. [27] M.J. Martinez Bueno, A. Aguera, M. Jose Gomez, M. Dolores Hernando, J.F. Garcia-Reyes, A.R. Fernandez-Alba, Application of liquid chromatography/quadrupole-linear ion trap mass spectrometry and time-of-flight mass spectrometry to the determination of pharmaceuticals and related contaminants in wastewater, Anal. Chem. 79 (2007) 9372–9384. [28] Z.X. Li, S. Yuan, C.C. Qiu, Y.J. Wang, X.J. Pan, J.L. Wang, C.W. Wang, J.A. Zuo, Effective degradation of refractory organic pollutants in landfill leachate by electro-peroxone treatment, Electrochim. Acta 102 (2013) 174–182. [29] H. Wang, B. Bakheet, S. Yuan, X. Li, G. Yu, S. Murayama, Y. Wang, Kinetics and energy efficiency for the degradation of 1,4-dioxane by electro-peroxone process, J. Hazard. Mater. 294 (2015) 90–98. [30] H. Wang, S. Yuan, J. Zhan, Y. Wang, G. Yu, S. Deng, J. Huang, B. Wang, Mechanisms of enhanced total organic carbon elimination from oxalic acid solutions by electro-peroxone process, Water Res. 80 (2015) 20–29. [31] X. Li, Y. Wang, S. Yuan, Z. Li, B. Wang, J. Huang, S. Deng, G. Yu, Degradation of the anti-inflammatory drug ibuprofen by electro-peroxone process, Water Res. 63 (2014) 81–93. [32] Y. Li, W. Shen, S. Fu, H. Yang, G. Yu, Y. Wang, Inhibition of bromate formation during drinking water treatment by adapting ozonation to electro-peroxone process, Chem. Eng. J. 264 (2015) 322–328. [33] U. von Gunten, Ozonation of drinking water: Part I. oxidation kinetics and product formation, Water Res. 37 (2003) 1443–1467. [34] E.L. Yong, Y.P. Lin, Kinetics of natural organic matter as the initiator, promoter, and inhibitor, and their influences on the removal of ibuprofen in ozonation, OzoneSci. Eng 35 (2013). [35] J. Staehelin, J. Hoigne, Decomposition of ozone in water in the presence of organic solutes acting as promoters and inhibitors of radical chain reactions, Environ. Sci. Technol. 19 (1985) 1206–1213. [36] C. von Sonntag, U. von Gunten, Chemistry of Ozone in Water and Wastewater Treatment, IWA publishing, 2012. [37] S.K. Dubey, R.N. Saha, H. Jangala, S. Pasha, Rapid sensitive validated UPLC–MS method for determination of venlafaxine and its metabolite in rat plasma: application to pharmacokinetic study, J.pharm. Anal. 3 (2013) 466–471. [38] B. Bakheet, S. Yuan, Z. Li, H. Wang, J. Zuo, S. Komarneni, Y. Wang, Electro-peroxone treatment of Orange II dye wastewater, Water Res. 47 (2013) 6234–6243. [39] C. Qiu, S. Yuan, X. Li, H. Wang, B. Bakheet, S. Komarneni, Y. Wang, Investigation of the synergistic effects for p-nitrophenol mineralization by a combined process of ozonation and electrolysis using a boron-doped diamond anode, J. Hazard. Mater. 280 (2014) 644–653. [40] G.V. Buxton, C.L. Greenstock, W.P. Helman, A.B. Ross, Critical review of rate constants for reactions of hydrated electrons, hydrogenatoms and hydroxyl radicals (OH/O− ) in aqueous solution, J. Phys. Chem. Ref. Data 17 (1988) 513–886.