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Removal of pharmaceuticals in water by introduction of ozonated microbubbles
Accepted Manuscript Removal of Pharmaceuticals in Water by Introduction of Ozonated Microbubbles Takashi Azuma, Kana Otomo, Mari Kunitou, Mai Shimizu, Kaori Hosomaru, Shiori Mikata, Yoshiki Mino, Tetsuya Hayashi PII: DOI: Reference:
S1383-5866(18)32419-5 https://doi.org/10.1016/j.seppur.2018.11.059 SEPPUR 15109
To appear in:
Separation and Purification Technology
Received Date: Revised Date: Accepted Date:
14 July 2018 22 September 2018 16 November 2018
Please cite this article as: T. Azuma, K. Otomo, M. Kunitou, M. Shimizu, K. Hosomaru, S. Mikata, Y. Mino, T. Hayashi, Removal of Pharmaceuticals in Water by Introduction of Ozonated Microbubbles, Separation and Purification Technology (2018), doi: https://doi.org/10.1016/j.seppur.2018.11.059
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Removal of Pharmaceuticals in Water by Introduction of Ozonated Microbubbles
Author names: Takashi Azuma*, Kana Otomo, Mari Kunitou, Mai Shimizu, Kaori Hosomaru, Shiori Mikata, Yoshiki Mino, Tetsuya Hayashi
Affiliation: Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka, 569-1094, Japan
*Corresponding author: Takashi Azuma Affiliation: Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka, 569-1094, Japan Tell: +81-72-690-1055, Fax: +81-72-690-1055 e-mail address: [email protected], [email protected]
Key words: Ozone-microbubble (O3-MB), Advanced oxidation processes (AOPs), Pharmaceuticals and personal care products (PPCPs), Removal efficiency, Water treatment system
Declarations of interest: None
1
Abstract Ozonated-microbubble (O3-MB) was applied to remove 39 pharmaceuticals in 10 therapeutic
classes
(antivirals,
antibacterials,
anticancer
drugs,
psychotropics,
antihypertensives, analgesic-antipyretics, contrast media, bronchodilators, antipruritics, and herbal medicines) in water and the results were compared with those given by O3 alone and combined treatments with UV, and/or H2O2, or both. The summarized results clearly indicate that O3-MB based treatments significantly (P < 0.01) enhanced removal rates by 8%–34% to O3 alome, and removal rates of >90% (>80%) were attained for 33 (37) compounds. Introduction of MB technology was indispensable to improve degradation of famciclovir (anti-viral), bicalutamide (anti-cancer), sulpiride (phychotropic) and acetaminophen glucuronide (analgesic-antipyretic) over 96.0%. Recalcitrant properties of all contrast media type compounds (iohexol, ioversol, iopromide, iomeprol and iopamidol) against both O3 and O3-MB were significantly improved by combined treatment with UV, and removal rates became 93.8%-98.8% from 0%-52.0%, indicating effectiveness of combined use of photolysis more than oxidation by hydroxyl radicals. Combination of UV and/or H2O2 with O3-MB increased the reaction rate constant by 2.9–5.5 times in average relative to O3 and O3-MB. In addition, MB treatment improved O3 consumption up to 2.8 times higher than the O3 treatments. These results indicate that the combined treatments of O3-MB with UV and/or H2O2 could minimize the environmental pollutant load of pharmaceuticals discharged into rivers. To the best of our knowledge, this is the first investigation which showed enhancement of removal rates of multiple pharmaceuticals together with combined use of UV and/or H2O2.
2
1. Introduction Modern society is supported by use of vast amounts of chemical compounds. The Chemical Abstracts Service lists up 143 million chemical species in 2018, more than double the 60 million listed in 2011 [1]. In our highly urbanized society, pollutants derived from the used and metabolized chemical compounds are leached in wastewater and transferred to wastewater treatment plants (WWTPs) via sewers for biological treatment and disinfection [2, 3]. However, highly hydrophilic compounds, such as pharmaceuticals, tend to be recalcitrant to the biological treatment processes usually operated in WWTPs [4]. The undegraded compounds then flow into rivers. WWTPs are now the main source of pollutants discharged into rivers [2, 5], and new environmental pollution problems have emerged not only in rivers, but also in lakes and even in the seas [6, 7]. Some pharmaceuticals in rivers are attenuated by photodegradation by sunlight, biodegradation by microorganisms, or sorption onto sediments [8, 9]. However, the meminders are resistant to these factors and so evoke concern for their toxicological effects on river ecosystems [10, 11]. Pharmaceuticals are useful for keeping our lives in healthy condition and sometimes indispensable for remedy, so restrictions on their use will not reduce the problems [12]. As the use of pharmaceuticals in Japan is the second largest in the world [13], it is important to develop new advanced water treatment systems and to evaluate their efficiency in order to reduce the pollutant loads discharged into rivers [4, 14]. Advanced treatment by ozone (O3), which is highly oxidative and is effective for decoloration, deodorization, disinfection [15], is effective for the removal of environmental pollutants such as persistent organic pollutants, endocrine-disrupting chemicals, and pharmaceuticals [16, 17]. In addition, advanced oxidation processes (AOPs) combining O3 with UV, hydrogen peroxide (H2O2), or both are known to improve removal efficiency [18, 19]. However, the solubility of O3 in water is not particularly high; 1.010-6 mol/m3·Pa to
3
1.310-4 mol/m3·Pa (although it is about 10 to 20 times higher that those of oxygen and nitrogen), so that O3 gas injected into the liquid phase remained in the vapor phase without reacting with pollutants in the water and passed through the reacting zone [20, 21]. Therefore, more effective usage of the O3 generated is important for improving rates of removal and cost efficiency [22, 23]. In recent years, microbubble (MB) technologies have been developed in Japan [24, 25], and the evaluation of its efficiency is growing rapidly in various research fields [26, 27]. MBs are commonly defined as small bubbles having diameters of <100 m [28, 29]. A conflict sometimes occurs in the use of terminology: A term ‘fine bubbles (FBs)’ is often used instead of ‘MBs’ [29, 30]. MBs have specific properties distinct from the familiar millimeter-scale macrobubbles (nomal bubbles). They rise slowly on account of their very big surface-tovolume ratio, and so they are stable for much longer than normal macrobubbles. In addition, surface tension can cause a high interior pressure, causing the dissolution of the gas in the surrounding water, leading to the shrinkage and collapse of the microbubbles [28, 31]. These properties lead researchers to propose the use of MB techniques for ozonation (ozonated microbubble: O3-MB) for the removal of environmental pollutants by enhanced water treatment systems [26, 27]. Such a limited use prompted to apply this O3-MB technique to the treatment of pharmaceuticals for the first time. In this report, the efficiency of removal of 39 pharmaceuticals in 10 therapeutic classes by O3-MB treatment alone was firstly investigated and the results were compared with those obtained by combined use of UV, H2O2, or both (O3-MB/UV, O3-MB/H2O2, and O3-MB/UV/H2O2). Finally, the merit of using O3-MB was discussed in comparison with the conventional O3 treatment.
2. Materials and methods 2.1 Pharmaceuticals and reagents
4
Investigation was made for 39 pharmaceuticals and their metabolites previously detected in hospital effluent, sewage, and river water [6, 32, 33]. The 39 compounds were grouped into 10 therapeutic class: (1) antivirals (aciclovir, famciclovir, and penciclovir); (2) antibacterials (cefdinir, ciprofloxacin, clarithromycin, and levofloxacin); (3) anticancer drugs (bicalutamide, bortezomib, bortezomib acid, capecitabine, cyclophosphamide, doxifluridine, etoposide, tamoxifen, 4-hydroxytamoxifen, and tegafur); (4) psychotropics (carbamazepine, 2-hydroxy carbamazepine, 3-hydroxy carbamazepine, and sulpiride); (5) antihypertensives (losartan, losartan carboxylic acid, olmesartan, and olmesartan medoxomil); (6) analgesic-antipyretics (acetaminophen, acetaminophen glucuronide, acetaminophen sulfate, and loxoprofen); (7) contrast media (iohexol, iomeprol, iopamidol, iopromide, and ioversol); (8) bronchodilators (caffeine and theophylline); (9) antipruritic (crotamiton); and (10) herbal medicines (berberine and puerarin). The physicochemical properties of the compounds are summarized in Table S1. All analytical standards were of high purity (>98%) and were purchased from AdooQ BioScience LLC (Irvine, CA, USA), Carbosynth Ltd. (Berkshire, UK), Cayman Chemical Co. (Ann Arbor, MI, USA), KareBay Biochem, Inc. (Deer Park Drive, NJ, USA), LC Laboratories Inc. (Woburn, MA, USA), LKT Laboratories Inc. (St. Paul, MN, USA), MedChemexpress Co., Ltd. (Deer Park Drive, NJ, USA), Nacalai Tesque, Inc. (Kyoto, Japan), Santa Cruz Biotechnology, Inc. (Santa Cruz, CA, USA), Sigma-Aldrich Co., LLC (St. Louis, MO, USA), Tokyo Chemical Industry Co., Ltd. (Tokyo, Japan), Toronto Research Chemicals Inc. (Toronto, Ontario, Canada), and Wako Pure Chemical Industries, Ltd. (Osaka, Japan). Liquid chromatography – mass spectrometry (LC-MS)-grade solvents (methanol and acetone), hydrogen peroxide, formic acid, hydrochloric acid, ammonia, and ascorbic acid were purchased from Wako Pure Chemical Industries.
5
2.2 O3-MB treatment All experiments were investigated in a semi-batch-scale acrylic batch reactor with an interior diameter of 10 cm and a height of 30 cm (effective volume of 2.2 L; Fig. S1). The internal temperature was maintained at 20 °C by circulating water through an external water jacket using a thermostat water circulator (CTR-320, AGC Techno Glass Co. Ltd., Tokyo, Japan). The solution was agitated continuously at 400 rpm with a magnetic stirrer (SRS710DA, Advantec Toyo Kaisha, Ltd., Tokyo, Japan) attached on the bottom surface of the reactor. The removal experiments were performed in Milli-Q water which contain each pharmaceutical of 500 ng/L, the values of which was previously determined based on the average of concentrations found in WWTPs and hospital effluents (10 ng/L to several g/L) [33, 34]. Ultra-performance LC–tandem MS (UPLC–MS/MS) was used for estimation of concentration of each pharmaceutical to ensure sensitivity of detection of removal efficiency after pretreatment by solid-phase extraction (SPE) as described in Section 2.3. O3 was generated by an ozone generator (ED-OG-R6, Ecodesign Inc., Saitama, Japan). and injected continuously into the reactor at a flow rate of 0.3 L/min and a concentration at 6.5 mg/L, corresponding to a feed rate of 1.0 mg/L/min. This feed rate was the same as the one used in WWTPs (6 mg/L for 20 min) [35] and previous studies of the removal of pharmaceuticals by ozonation [36, 37]. For the O3-MB treatments, O3 was introduced inside of a microbubble generator by a pump with a circulation volume of 1 L/min. Pressure at 20 kPa was used to generate microbubbles having a modal pore diameter of 33 m (Fig. S2). The O3 consumption was calculated from the balance in both gas and liquid phases during the experiment [22, 38]. UV irradiation was supplied by a 9-W low-pressure mercury lamp (TCGU60-250ZP, Miyakawa Corp., Tokyo, Japan) with a peak wavelength of 254 nm and an intensity of 2.8 mW/cm2 as used in the previous studies [39]. The UV lamp was introduced into the reactor
6
and kept separate from the water by a quartz jacket. The initial H2O2 concentration was set at 5 mg/L, as in previous studies [40]. A portion of the reactor solution (160 mL, 4 × 40 mL) was sampled at 0, 2, 5, 10, 20 and 30 min after the experiment, while at 0, 1, 2, 3, 5 and 10 min in the O3-MB experiments, respectively, for measurement of concentrations. Duration of the reaction was changed by reflecting the average contact time in actual WWTPs that use ozonation before discharge into rivers in Japan (15 ± 5 min) [35], and the values reported in the previous reports [36, 37]. Ascorbic acid was immediately added to each sample to a final concentration of 1.0 g/L to remove residual O3 and hydrogen peroxide and to quench reactive oxygen species such as OH·, guaranteeing the end of the oxidation reactions [41]. The samples were then stored at 4 °C in dark and processed within 24 h. Each solution was pretreated by SPE or ultrasonic extraction and analyzed by UPLC-MS/MS as described in Section 2.3.
2.3 Analytical procedures SPE and UPLC–MS/MS were used for all analyses as previously described [42]. In brief, four 40-mL aliquots were taken for analysis of each sample and filtered separately through a glass fiber filter (GF/B, 1-m pore size, Whatman, Maidstone, UK). Four SPE cartridges (Oasis HLB, 200 mg; Waters Corp., Milford, MA, USA) were preconditioned for each sample by washing first with 3 mL methanol and then with 3 mL Milli-Q water adjusted to pH 3 with 1 N HCl. A known amount of each compound was spiked into two aliquots for analysis to a final concentration of 500 ng/L. The spiked aliquots were then applied to two different SPE cartridges at 1 mL/min. Similarly, unspiked aliquots were applied to the remaining two cartridges. All cartridges were washed with 6 mL Milli-Q water adjusted to pH 3 and then dried by vacuum pump. Finally, the adsorbed pharmaceuticals were eluted in a stepwise manner with 3 mL acetone + 3 mL methanol, 2 mL 10% (v/v) formic acid in acetone, 2 mL
7
10% (v/v) formic acid in methanol, and finally 2 mL 5% ammonia–methanol (v/v). Each combined eluate solution was evaporated to dryness under a gentle stream of nitrogen gas at 37 °C. The residue was solubilized in 200 L of a 90:10 (v/v) mixture of 0.1% formic acid solution in methanol, and 10 L of this solution was analyzed by UPLC-MS/MS on a reverse-phase UPLC device fitted with a UPLC BEH C18 column (2.1 mm × 100 mm, 1.7 m; Waters Acquity, Waters Corp.). For simultaneous analysis of the target compounds, a gradient elution program was used at 60 °C with a solvent mix of 0.1% formic acid (v/v) in Milli-Q water (A) and methanol (B) at a flow rate of 0.35 mL/min under a program of 0.0 to 2.0 min (10% B), 2.0 to 8.0 min (25% B), 8.0 to 14.0 min (55% B), 14.0 to 16.0 min (55% B), 16.0 to 19.0 min (90% B), 19.0 to 19.2 min (100% B), 19.2 to 21.2 min (100% B), 21.2 to 24.0 min (10% B), and 24.0 to 26.0 min (10% B). The UPLC system was coupled to a TQD tandem quadrupole mass spectrometer (Waters Corp.) equipped with an electrospray ionization source and operated both in positive and negative ion modes. The samples were analyzed by time-scheduled acquisition for multiple reaction monitoring based on the combination of precursor and product ions. Detailed information on the analytical parameters used for LC-MS/MS is given in Table S2.
2.4 Method validation Six-point standard calibration curves were constructed for quantification at a concentration range from 0.5 to 200 ng/mL. The individual linear calibration curves for each compound were obtained (r2 > 0.99) by selecting a weighting factor of 1/x. The blank data were subtracted from the spiked sample data to account for matrix effects and loss during sample extraction [32]. Recovery rates were calculated from the deviations between the spiked data and the standard data; values ranged from 60% to 110%, generally similar to those reported in previous studies of pharmaceuticals in river and sewage samples [33, 43]. The limits of
8
detection and of quantification were calculated as the concentrations at signal-to-noise ratios of 3 and 10, respectively, according to methods used for pharmaceuticals [43].
3. Results and discussion 3.1 Enhancement of removal rates To show the aim of the present study clearly, the results were explained from the standard O3 treatments. Treatments with O3 removed >90% of 26 compounds within 5 min (Fig. 1). These results are similar to previous results [14, 17, 18]. Some compounds were, however, fairly resistant: removal rares of bortezomib acid (48%), loxoprofen (48%), bicalutamide (43%), cyclophosphamide (22%) and acetaminophen glucuronide (19%). These compounds were classified as gradually degradable by ozonation. The pharmaceuticals in the class of contrast media were resistant to highly resistant iohexol (35%), ioversol (33%), iopromide (9%), iomeprol (6%) and iopamidol (0%). This high recalcitrance of contrast media to ozonation is similar to the removal rates (10% to 42%) reported previously [23, 44, 45]. Combined treatments of O3 with UV and UV/H2O2 were found to improve these low removal rates. In particular, combined treatments with O3/UV and O3/UV/H2O2 greatly improved the removal of bortezomib acid (83%–100%), iohexol (99%), ioversol (93%–97%), iopromide (94%–98%), iomeprol (96%–99%), and iopamidol (95%–97%). In contrast, increment of reaction rate by O3/H2O2 was as low as 0%–36%. These results indicate that the main improvement in O3/UV and O3/UV/H2O2 is due to direct photolysis by UV, meaning participation of OH· generated by combined use of O3 and UV as described previously [46]. This interpretation is supported further by the results that the contrast media type compounds absorb energy mainly in the region of 220–280 nm [47], and that their half-lives under UV were only 0.5 min for iohexol [47], 0.2–6 min for iopamidol [47, 48], and 0.5 min for iopromide [47].
9
The present new technique joining O3 with MB opened a new approach to remove vast kinds of pharmaceuticals. Namely, O3-MB increased removal rates by 8%–34% compared with O3 alone, and could remove >90% of 26 to 32 compounds (Table 1). O3-MB also enhanced the removal of the recalcitrant compounds against O 3: acetaminophen glucuronide (32% from 19%), bortezomib acid (88% from 48%), and loxoprofen (82% from 48%). Combined use of UV (O3-MB/UV) further improved the removal rate of acetaminophen glucuronide to 80% and all compounds belong to contrast media as previously observed in O3/UV and O3/UV/H2O2. It must be stressed that combined use of UV and H2O2 (O3MB/UV/H2O2) alone enhanced the removal rate of famciclovir and bicalutamide to attain 96% and 99%, respectively, together with complete removal of bortezomib acid. Combined use of H2O2 (O3-MB/H2O2) was effective similar to O3-MB/UV/H2O2, but did not have a power enough to remove famciclovir and contrast media type compounds. MB treatment was concluded to be essential for removal of famciclovir, bicalutamide, sulpiride, acetaminophen glucuronide and loxoprofen. Removal efficiencies were estimated as 81% ± 31% (mean ± SD) by O3-MB, 90% ± 19% by O3-MB/UV, 85% ± 24% by O3-MB/H2O2, and 94% ± 15% by O3-MB/UV/H2O2. On account of the remained two compounds, cyclophosphamide and acetaminophen sulfate whose removal rates were still low (32% for the former and 74% for the latter), we are waiting for appearance of new technologies which will overcome their recalcitrance. The present analytical results also indicate that the amounts of dissolved organic carbon (DOC) did not change before and after the present experiments, in accord with the previous results which showed remaining of the degraded products as stable compounds such as in the form of organic acids [49, 50].
Further investigation seems necessary in relation to
degradation mechanisms with characterization of chemical structure of the reaction products [51, 52] and their impact on the environment and organisms [53, 54].
10
Table 1. Efficiency of removal of target pharmaceuticals during 5-min O3 treatment: O3 based treatment system and O3-MB based treatment system. Removal rate (%) O3 based treatment system
O3-MB based treatment system
Therapeutic Compound
O3 -
class O3
Aciclovir
O3/UV
O3/H2O2
O3
O3 -
/UV/H2O2
MB
MB/ UV
O3-MB
O3-MB/UV/
/H2O2
H2 O2
100.0
99.6
100.0
98.1
100.0
100.0
100.0
100.0
63.3
31.0
22.1
19.2
66.1
65.8
78.9
96.0
Penciclovir
100.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
Cefdinir
100.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
76.7
98.4
48.4
100.0
99.0
90.1
98.5
94.8
79.6
45.5
60.2
100.0
96.5
87.0
99.4
Levofloxacin
100.0
98.5
100.0
70.5
100.0
99.6
99.8
100.0
Bicalutamide
42.9
47.6
39.2
15.4
38.7
35.3
10.3
98.9
100.0
97.8
72.7
99.9
62.7
71.2
98.5
99.3
Bortezomib acid
48.4
100.0
64.2
82.6
87.8
58.8
100.0
100.0
Capecitabine
99.5
97.3
97.1
85.0
100.0
100.0
100.0
100.0
21.5
0.0
13.9
12.0
14.0
30.2
26.1
32.0
99.9
99.0
100.0
97.1
100.0
100.0
100.0
100.0
Famciclovir
Anti-viral
Ciprofloxacin Anti-bacterial Clarithromycin
Bortezomib
Cyclophosphamide Anti-cancer Doxifluridine Etoposide
100.0
99.9
99.5
100.0
100.0
100.0
100.0
100.0
Tamoxifen
100.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
4-Hydroxy tamoxifen
100.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
Tegafur
100.0
100.0
100.0
94.0
100.0
100.0
100.0
100.0
99.9
100.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
3-Hydroxy carbamazepine
99.4
95.2
100.0
100.0
100.0
100.0
100.0
100.0
Sulpiride
85.4
32.8
67.4
39.7
98.6
80.3
92.7
82.1
Losartan
100.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
99.9
97.3
100.0
95.1
100.0
99.9
99.7
100.0
Olmesartan medoxomil
99.8
97.1
99.2
63.2
100.0
99.8
100.0
100.0
Acetaminophen
99.9
91.0
100.0
95.2
99.8
98.7
98.5
94.4
Carbamazepine 2-Hydroxy carbamazepine Psychotropic
Losartan carboxylic acid
Anti-
Olmesartan
hypertensive
Acetaminophen glucuronide
Analgesic-
19.2
52.0
26.6
16.9
31.9
80.2
84.2
100.0
Acetaminophen sulfate
antipyretic
60.8
73.5
37.0
65.8
53.5
42.8
64.5
34.7
Loxoprofen
47.5
63.6
0.0
14.4
81.6
67.7
70.2
78.0
Iohexol
34.8
98.8
0.0
98.5
52.0
98.3
60.8
99.9
5.6
99.1
0.0
95.8
30.9
94.9
44.4
94.6
0.0
94.8
0.0
97.2
0.0
96.2
39.2
89.5
Iomeprol Iopamidol
Contrast media
Iopromide Ioversol Caffeine
8.6
94.1
45.3
98.0
44.5
97.6
60.4
87.8
33.1
97.0
0.0
93.3
11.6
93.8
34.6
85.4
95.9
53.6
93.9
27.0
97.5
97.0
91.2
93.5
100.0
99.8
98.4
74.6
100.0
99.7
99.9
98.8
100.0
100.0
100.0
99.4
100.0
100.0
100.0
100.0
100.0
100.0
100.0
99.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
99.9
100.0
100.0
100.0
100.0
Bronchodilator Theophylline Crotamiton
Anti-pruritic
Berberine Herbal medicine Puerarin
11
3.2 Reaction kinetics and distribution of reaction rate constant Figure 1 shows the removal of doxifluridine (a representative compound immediately removed by O3) and sulpiride (relatively rapidly removed by O3). The reactions followed pseudo-first-order kinetics (r2 > 0.90), as previously reported [55]. Table 2 shows the distribution of reaction rate constant for all compounds grouped in 10 therapeutic classes. The reaction rate constants differed between O3 and O3-MB treatments (P < 0.01 (Fig. S3)). Under O3 treatments, values were 1.1 ± 1.1 min−1 by O3, 1.0 ± 0.9 min−1 by O3/UV, 1.1 ± 1.2 min−1 by O3/H2O2, and 0.8 ± 0.8 min−1 by O3/UV/H2O2. Under O3-MB treatments, on the other hand, 2 to 7-fold increase in the values were observed: 2.5 ± 2.4 min−1 by O3-MB, 2.0 ± 2.1 min−1 by O3-MB/UV, 2.2 ± 2.2 min−1 by O3-MB/H2O2, and 3.0 ± 2.5 min−1 by O3MB/UV/H2O2. These results support to conclude that the O3-MB treatment is more effective than the conventional O3 treatment. The reaction rate constants differed also among pharmaceutical classes. Both O3 and O3MB treatments rapidly removed all antihypertensives (0.4–6.6 min−1; half-lives of 0.1–2.0 min) and herbal medicines (0.9–6.8 min−1 ; half-lives of 0.1–0.8 min). However, the rate constants of the other class-pharamaceuticals varied widely: 0.04 to 4.9 min−1 for antivirals, 0.09 to 6.0 min−1 for antibacterials, 0.001 to 7.3 min−1 for anticancer drugs, 0.08 to 6.3 min−1 for psychotropics, 0.01 to 1.7 min−1 for analgesic-antipyretics, 0.001 to 1.0 min−1 for contrast media, and 0.08 to 6.6 min−1 for bronchodilators. In the cases for the combined treatments including UV, O3/UV, O3/UV/H2O2, O3-MB/UV and O3-MB/UV/H2O2 photolysis was thought to play a key role in the observed significant enhancement of the removal of bortezomib acid, iohexol, iomeprol, iopamidol, iopromide, and ioversol for 2.3–332 times relative to O3 and O3-MB [56] (see Section 3.1). On the next step, any new devices which permit real time characterization of correlation between chemical structure and removal rate [57, 58] are to be introduced in future for further enhancement of
12
the efficiency of the present treatment system. Reaction time (min) 0 0
0
Reaction time (min)
2
4
2
6
4
6
8
10
8
10
0
(1)
O3
O O33 O3/UV
-2 Ln (C/C0)
Ln (C/C0)
O3/UV O 3/UV
O3/H2O2
O3/H2O2 O 3/H2O2
-2
O3/UV/H2O2
O3/UV/H2O2 O 3/UV/H2O2
-4 -4
MB-O3 MB-O3 O 3-MB MB-O3/UV O MB-O3/UV 3-MB/UV
-6 -6
MB-O3/H2O2 O -MB/H2O2 3MB-O3/H2O2
O -MB/UV/H2O2 MB-O3/UV/H2O2 3MB-O3/UV/H2O2
-8 -8
線形 (O3) 線形 (O3)
Reaction time (min) 0
2 0
-2 Ln (C/C0)
Ln (C/C0)
0
Reaction time (min)
4
2
6
4
6
線形 (O3/UV)
線形 (O3/UV)
8
10
8
10
0
線形 (O3/H2O2)
線形 (O3/H2O2)
O3 線形 O O33線形 (O3/UV/H2O2) O3/UV (O3/UV/H2O2) 線形 (MB-O3) O /UV (MB-O3) O3/UV 3線形 線形 (MB-O3/UV) O3/H2O2
O3/H2O2 O /H2O(MB-O3/UV) 3線形 2
-2
線形 (MBO3/UV/H2O2
O3/UV/H2O2 O 3/UV/H2O2 O3/H2O2)
線形 (MB-
線形 (MB-
-4 -4
MB-O3 O3/H2O2) O MB-O3 3-MB O3/UV/H2O2) 線形 (MB-
MB-O3/UV O3/UV/H2O2) O MB-O3/UV 3-MB/UV
-6 -6
MB-O3/H2O2 MB-O3/H2O2 O 3-MB/H2O2
(2)
MB-O3/UV/H2O2 O MB-O3/UV/H2O2 3-MB/UV/H2O2
-8 -8
線形 (O3) 線形 (O3) 線形 (O3/UV)
線形 (O3/UV) Figure 2. Relative residual concentrations of pharmaceuticals (C0, initial concentration; 線形 (O3/H2O2)
C, concentration after reaction): (1) doxifluridine, (2) sulpiride.
線形 (O3/H2O2)
線形 線形 (O3/UV/H2O2) (O3/UV/H2O2) 線形 (MB-O3)
線形 (MB-O3)
線形 (MB-O3/UV)
線形 (MB-O3/UV) 線形 (MBO3/H2O2) 線形 (MB線形 (MBO3/H2O2) O3/UV/H2O2) 線形 (MB-
O3/UV/H2O2)
13
Table 2. First-order rate constants of target pharmaceuticals by using O3 and O3-MB based water treatment systems. Reaction rate (min-1) Therapeutic
O3-based treatment system
Compound class
O3-MB based treatment system O3 -
O3 -
O3 -
O3 -
MB
MB/UV
MB/H2O2
MB/UV/H2O2
3.068
3.258
3.714
0.185
0.215
0.267
0.513
1.106
4.007
2.724
4.820
4.875
1.362
1.320
6.016
5.724
5.981
4.920
0.178
0.778
0.148
2.325
0.698
0.492
0.747
0.541
0.273
0.087
0.173
2.504
0.698
0.445
1.050
2.205
0.617
2.645
0.242
2.615
1.157
1.393
2.294
Bicalutamide
0.037
0.109
0.019
0.015
0.143
0.073
0.078
0.912
Bortezomib
0.001
0.704
0.544
1.387
0.104
0.272
0.652
0.856
Bortezomib acid
0.194
1.548
0.116
0.792
0.280
0.190
5.334
2.241
Capecitabine
1.024
0.683
0.685
0.228
3.055
2.562
2.471
4.180
Cyclophosphamide
0.020
0.022
0.014
0.048
0.021
0.048
0.053
0.080
Doxifluridine
1.399
0.897
2.029
0.674
5.100
1.991
2.462
5.318
Etoposide
1.797
1.349
1.066
2.389
3.864
3.364
5.616
6.254
Tamoxifen
1.151
0.896
0.693
0.693
0.693
6.109
5.991
6.477
4-Hydroxy tamoxifen
1.099
0.973
0.896
1.151
1.099
1.194
2.639
2.639
Tegafur
2.097
3.129
2.772
0.638
7.281
3.306
3.188
6.845
Carbamazepine
1.943
1.640
1.680
1.894
6.314
6.268
5.554
5.305
2.913
2.642
3.883
4.158
4.135
6.225
2.317
5.613
3-Hydroxy carbamazepine
0.909
0.383
3.809
1.704
4.871
6.048
6.281
4.950
Sulpiride
0.195
0.082
0.157
0.086
0.652
0.320
0.372
0.373
Losartan
2.394
2.534
2.272
1.857
5.451
2.768
5.971
5.609
O3
O3/UV
O3/H2O2
1.320
1.128
1.782
0.772
2.944
0.114
0.042
0.082
0.063
Penciclovir
2.102
2.087
2.233
Cefdinir
2.617
2.639
0.276
Clarithromycin Levofloxacin
Aciclovir Famciclovir
Anti-viral
Ciprofloxacin
O3/UV/H2O2
Anti-bacterial
Anti-cancer
2-Hydroxy carbamazepine Psychotropic
Losartan carboxylic acid
Anti-
1.684
1.557
1.242
0.723
3.332
1.789
3.033
6.593
Olmesartan
hypertensive
1.389
0.758
2.471
0.350
3.336
1.315
1.271
6.342
Olmesartan medoxomil
1.333
0.665
0.876
0.431
1.518
1.280
2.183
2.186
Acetaminophen
1.527
0.658
1.676
0.671
1.302
0.671
0.613
0.452
Acetaminophen glucuronide
Analgesic-
0.102
0.108
0.110
0.071
0.137
0.274
0.348
1.493
Acetaminophen sulfate
antipyretic
0.064
0.118
0.122
0.288
0.108
0.084
0.163
0.092
Loxoprofen
0.043
0.216
0.012
0.158
0.358
0.282
0.165
0.449
Iohexol
0.039
0.823
0.031
0.599
0.109
0.734
0.587
1.027
0.015
0.849
0.042
0.314
0.039
0.651
0.089
0.635
0.001
0.591
0.016
0.635
0.008
0.561
0.312
0.573
Iopromide
0.030
0.491
0.039
0.678
0.082
0.594
0.117
0.581
Ioversol
0.028
0.658
0.013
0.452
0.017
0.507
0.059
0.513
Caffeine
0.148
0.099
0.242
0.082
0.541
0.438
0.347
0.393
2.698
1.244
0.710
0.179
6.554
1.035
1.377
0.682
Iomeprol Contrast Iopamidol media
Bronchodilator Theophylline Crotamiton
Anti-pruritic
2.957
2.436
2.602
2.079
5.663
5.808
5.771
5.198
Berberine
Herbal
2.794
1.901
1.688
0.920
4.052
5.412
2.235
6.613
Puerarin
medicine
3.409
2.110
3.153
1.547
6.817
3.328
3.181
6.475
14
3.3 Efficiency of O3-MB treatment based on O3 consumption The O3-MB based treatments consumed up to 2.8-fold O3 than the O3 treatments (Fig. 2). Mean improvements were 2.0 ± 0.6 times by O3-MB, 1.0 ± 0.1 times by O3-MB/UV, 2.8 ± 0.2 times by O3MB/H2O2, and 1.3 ± 0.1 times by O3-MB/UV/H2O2. These results agreed with the distribution of reaction rate constants as shown in Table 2. The removal rates increased as effective usage of O3 increased, although any significant correlation was not obserbed. Difficulty in characterization of the reaction rate constants was in that HO· has a higher oxidation potential (2.8 V) than ozone (2.1 V) [59], and thus will immediately react with O3 as strong quenching agents [60] together with its consumption due to unknown secondary reactions in water. Because of these side reactions, not all of the HO·contributed to the degradation of the test compounds [60, 61].
Ozone consumption (mg/L)
Ozone consumption (mg/L)
y = 0.434 x
O3 O3 O3 O3/UV
12 12
O3/H2O2 O3/UV O3/UV O3/UV/H2O2 MB-O3 O3/H2O2 O3/H2O2 MB-O3/UV MB-O3/H2O2 O3/UV/H2O2 O3/UV/H2O2 MB-O3/UV/H2O2 MB-O3 O3-MB 線形 (MB-O3/H2O2)
9 9 6
6 3
3 0 0
0 0
2
2
4
6
8
4 6 (min) 8 Reaction time
10
R2 = 0.953 y = 0.694 x R2 = 0.999 y = 0.445 x R2 = 0.985 y = 0.915 x R2 = 0.995
線形 (MB-O3/UV/H2O2) MB-O3/UV O -MB/UV 線形3 (MB-O3) 線形 (O3/UV/H2O2) y = 1.046 x MB-O3/H2O2 O3-MB/H 2O2 線形 (O3/UV) R2 = 0.996 線形 (O3) MB-O3/UV/H2O2 O3-MB/UV/H O 2 2 y = 0.712 x 線形 (O3/H2O2) R2 = 0.995 線形 (MB-O3/UV)
10
Reaction time (min)
y = 1.256 x R2 = 0.997 y = 1.163 x R2 = 1.000
Figure 2. Ozone consumption over time in each treatment system. Wastewater treatment using O3-MB has advantages. First, O3-MB treatment can reduce energy costs by enhancing O3 consumption relative to conventional O3 treatment, in which O3 diffuses quickly out of the liquid phase [20]. Second, although catalysts such as UV and H2O2 can improve efficiency, they are not essential for 15
O3-MB treatment. These advantages are effective not only for reducing the discharge of pharmaceuticals into the environment (environmentally friendly systems), but also in the construction and management of wastewater treatment plants [22, 23]. Research to develop O3-MB is expanding rapidly worldwide. In addition to environmental uses such as water purification and wastewater treatment, O3-MB can expect to find uses in agriculture for washing vegetables [30, 62] and in health for the disinfection of medical apparatus [63], and in treating hospital effluent [10, 64]). Our findings should be of value in developing new advanced water treatment systems to minimize the discharge of pharmaceuticals into rivers.
4. Conclusions Removal rates of 39 pharmaceuticals in 10 therapeutic classes (antivirals, antibacterials, anticancer drugs, psychotropics, antihypertensives, analgesic-antipyretics, contrast media, bronchodilators, antipruritics, and herbal medicines) in water were estimated by introduction of O3-MB, and the results were compared with those given by O3 alone and combined treatments with UV, and/or H2O2, or both. The results indicated that degradability of the O3-MB treatment enhanced removal rates by 8%–34% compared with O3 (P < 0.01) and 90% degradability was attained for 33 compounds (˃80% for 37 compounds). MB technology was indispensable to remove ˃90% of famciclovir (anti-viral), bicalutamide (anti-cancer), sulpiride (phychotropic) and acetaminophen glucuronide (analgesic-antipyretic). Recalcitrant properties of all contrast media type pharmaceuticals (iohexol, ioversol, iopromide, iomeprol and iopamidol) disappeared by combined treatment with UV, and removal rates became 94%-99% from 0%-52%. Combined use of UV (O3-MB/UV and O3MB/UV/H2O2) enhanced the reaction rate constants by 2.9–5.5 times in average relative to O3 and O3-MB. 16
Ozone consumption in O3-MB was up to 2.8 times higher than that in the O3 treatment. The results indicate that O3-MB as a new advanced water treatment system would minimize the discharge of pharmaceuticals into river environments.
Acknowledgments We acknowledge the Sumitomo Foundation (153018), Kurita Water and Environment Foundation (14E007), Maeda Engineering Foundation, and the Ministry of Education, Culture, Sports, Science and Technology of Japan (16K16218) for funding in the form of research grants and scholarships. We also thank the Promoting Academic Exchange Board of the Osaka University of Pharmaceutical Sciences for supporting our collaborative studies.
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25
Highlights
O3-MB was applied to remove 39 pharmaceuticals in 10 therapeutic classes in water. Over 90% removal rate was obtained for 33 compounds (>80% for 37 compounds). O3-MB enhanced removal efficiency by 8%–34% relative to the conventional O3. UV and/or H2O2 increased the reaction rate constant by 2.9–5.5 times relative to O3-MB. MB treatment improved O3 consumption up to 2.8 times higher than O3 treatments.
26
Graphical Abstract
Pharmaceuticals
OzoneMicrobubble O3-MB, O3-MB/UV, O3-MB/H2O2, O3-MB/UV/H2O2
0 25 50
27
1 0 0 1 5 0 ( m)
S1383-5866(18)32419-5 https://doi.org/10.1016/j.seppur.2018.11.059 SEPPUR 15109
To appear in:
Separation and Purification Technology
Received Date: Revised Date: Accepted Date:
14 July 2018 22 September 2018 16 November 2018
Please cite this article as: T. Azuma, K. Otomo, M. Kunitou, M. Shimizu, K. Hosomaru, S. Mikata, Y. Mino, T. Hayashi, Removal of Pharmaceuticals in Water by Introduction of Ozonated Microbubbles, Separation and Purification Technology (2018), doi: https://doi.org/10.1016/j.seppur.2018.11.059
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Removal of Pharmaceuticals in Water by Introduction of Ozonated Microbubbles
Author names: Takashi Azuma*, Kana Otomo, Mari Kunitou, Mai Shimizu, Kaori Hosomaru, Shiori Mikata, Yoshiki Mino, Tetsuya Hayashi
Affiliation: Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka, 569-1094, Japan
*Corresponding author: Takashi Azuma Affiliation: Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka, 569-1094, Japan Tell: +81-72-690-1055, Fax: +81-72-690-1055 e-mail address: [email protected], [email protected]
Key words: Ozone-microbubble (O3-MB), Advanced oxidation processes (AOPs), Pharmaceuticals and personal care products (PPCPs), Removal efficiency, Water treatment system
Declarations of interest: None
1
Abstract Ozonated-microbubble (O3-MB) was applied to remove 39 pharmaceuticals in 10 therapeutic
classes
(antivirals,
antibacterials,
anticancer
drugs,
psychotropics,
antihypertensives, analgesic-antipyretics, contrast media, bronchodilators, antipruritics, and herbal medicines) in water and the results were compared with those given by O3 alone and combined treatments with UV, and/or H2O2, or both. The summarized results clearly indicate that O3-MB based treatments significantly (P < 0.01) enhanced removal rates by 8%–34% to O3 alome, and removal rates of >90% (>80%) were attained for 33 (37) compounds. Introduction of MB technology was indispensable to improve degradation of famciclovir (anti-viral), bicalutamide (anti-cancer), sulpiride (phychotropic) and acetaminophen glucuronide (analgesic-antipyretic) over 96.0%. Recalcitrant properties of all contrast media type compounds (iohexol, ioversol, iopromide, iomeprol and iopamidol) against both O3 and O3-MB were significantly improved by combined treatment with UV, and removal rates became 93.8%-98.8% from 0%-52.0%, indicating effectiveness of combined use of photolysis more than oxidation by hydroxyl radicals. Combination of UV and/or H2O2 with O3-MB increased the reaction rate constant by 2.9–5.5 times in average relative to O3 and O3-MB. In addition, MB treatment improved O3 consumption up to 2.8 times higher than the O3 treatments. These results indicate that the combined treatments of O3-MB with UV and/or H2O2 could minimize the environmental pollutant load of pharmaceuticals discharged into rivers. To the best of our knowledge, this is the first investigation which showed enhancement of removal rates of multiple pharmaceuticals together with combined use of UV and/or H2O2.
2
1. Introduction Modern society is supported by use of vast amounts of chemical compounds. The Chemical Abstracts Service lists up 143 million chemical species in 2018, more than double the 60 million listed in 2011 [1]. In our highly urbanized society, pollutants derived from the used and metabolized chemical compounds are leached in wastewater and transferred to wastewater treatment plants (WWTPs) via sewers for biological treatment and disinfection [2, 3]. However, highly hydrophilic compounds, such as pharmaceuticals, tend to be recalcitrant to the biological treatment processes usually operated in WWTPs [4]. The undegraded compounds then flow into rivers. WWTPs are now the main source of pollutants discharged into rivers [2, 5], and new environmental pollution problems have emerged not only in rivers, but also in lakes and even in the seas [6, 7]. Some pharmaceuticals in rivers are attenuated by photodegradation by sunlight, biodegradation by microorganisms, or sorption onto sediments [8, 9]. However, the meminders are resistant to these factors and so evoke concern for their toxicological effects on river ecosystems [10, 11]. Pharmaceuticals are useful for keeping our lives in healthy condition and sometimes indispensable for remedy, so restrictions on their use will not reduce the problems [12]. As the use of pharmaceuticals in Japan is the second largest in the world [13], it is important to develop new advanced water treatment systems and to evaluate their efficiency in order to reduce the pollutant loads discharged into rivers [4, 14]. Advanced treatment by ozone (O3), which is highly oxidative and is effective for decoloration, deodorization, disinfection [15], is effective for the removal of environmental pollutants such as persistent organic pollutants, endocrine-disrupting chemicals, and pharmaceuticals [16, 17]. In addition, advanced oxidation processes (AOPs) combining O3 with UV, hydrogen peroxide (H2O2), or both are known to improve removal efficiency [18, 19]. However, the solubility of O3 in water is not particularly high; 1.010-6 mol/m3·Pa to
3
1.310-4 mol/m3·Pa (although it is about 10 to 20 times higher that those of oxygen and nitrogen), so that O3 gas injected into the liquid phase remained in the vapor phase without reacting with pollutants in the water and passed through the reacting zone [20, 21]. Therefore, more effective usage of the O3 generated is important for improving rates of removal and cost efficiency [22, 23]. In recent years, microbubble (MB) technologies have been developed in Japan [24, 25], and the evaluation of its efficiency is growing rapidly in various research fields [26, 27]. MBs are commonly defined as small bubbles having diameters of <100 m [28, 29]. A conflict sometimes occurs in the use of terminology: A term ‘fine bubbles (FBs)’ is often used instead of ‘MBs’ [29, 30]. MBs have specific properties distinct from the familiar millimeter-scale macrobubbles (nomal bubbles). They rise slowly on account of their very big surface-tovolume ratio, and so they are stable for much longer than normal macrobubbles. In addition, surface tension can cause a high interior pressure, causing the dissolution of the gas in the surrounding water, leading to the shrinkage and collapse of the microbubbles [28, 31]. These properties lead researchers to propose the use of MB techniques for ozonation (ozonated microbubble: O3-MB) for the removal of environmental pollutants by enhanced water treatment systems [26, 27]. Such a limited use prompted to apply this O3-MB technique to the treatment of pharmaceuticals for the first time. In this report, the efficiency of removal of 39 pharmaceuticals in 10 therapeutic classes by O3-MB treatment alone was firstly investigated and the results were compared with those obtained by combined use of UV, H2O2, or both (O3-MB/UV, O3-MB/H2O2, and O3-MB/UV/H2O2). Finally, the merit of using O3-MB was discussed in comparison with the conventional O3 treatment.
2. Materials and methods 2.1 Pharmaceuticals and reagents
4
Investigation was made for 39 pharmaceuticals and their metabolites previously detected in hospital effluent, sewage, and river water [6, 32, 33]. The 39 compounds were grouped into 10 therapeutic class: (1) antivirals (aciclovir, famciclovir, and penciclovir); (2) antibacterials (cefdinir, ciprofloxacin, clarithromycin, and levofloxacin); (3) anticancer drugs (bicalutamide, bortezomib, bortezomib acid, capecitabine, cyclophosphamide, doxifluridine, etoposide, tamoxifen, 4-hydroxytamoxifen, and tegafur); (4) psychotropics (carbamazepine, 2-hydroxy carbamazepine, 3-hydroxy carbamazepine, and sulpiride); (5) antihypertensives (losartan, losartan carboxylic acid, olmesartan, and olmesartan medoxomil); (6) analgesic-antipyretics (acetaminophen, acetaminophen glucuronide, acetaminophen sulfate, and loxoprofen); (7) contrast media (iohexol, iomeprol, iopamidol, iopromide, and ioversol); (8) bronchodilators (caffeine and theophylline); (9) antipruritic (crotamiton); and (10) herbal medicines (berberine and puerarin). The physicochemical properties of the compounds are summarized in Table S1. All analytical standards were of high purity (>98%) and were purchased from AdooQ BioScience LLC (Irvine, CA, USA), Carbosynth Ltd. (Berkshire, UK), Cayman Chemical Co. (Ann Arbor, MI, USA), KareBay Biochem, Inc. (Deer Park Drive, NJ, USA), LC Laboratories Inc. (Woburn, MA, USA), LKT Laboratories Inc. (St. Paul, MN, USA), MedChemexpress Co., Ltd. (Deer Park Drive, NJ, USA), Nacalai Tesque, Inc. (Kyoto, Japan), Santa Cruz Biotechnology, Inc. (Santa Cruz, CA, USA), Sigma-Aldrich Co., LLC (St. Louis, MO, USA), Tokyo Chemical Industry Co., Ltd. (Tokyo, Japan), Toronto Research Chemicals Inc. (Toronto, Ontario, Canada), and Wako Pure Chemical Industries, Ltd. (Osaka, Japan). Liquid chromatography – mass spectrometry (LC-MS)-grade solvents (methanol and acetone), hydrogen peroxide, formic acid, hydrochloric acid, ammonia, and ascorbic acid were purchased from Wako Pure Chemical Industries.
5
2.2 O3-MB treatment All experiments were investigated in a semi-batch-scale acrylic batch reactor with an interior diameter of 10 cm and a height of 30 cm (effective volume of 2.2 L; Fig. S1). The internal temperature was maintained at 20 °C by circulating water through an external water jacket using a thermostat water circulator (CTR-320, AGC Techno Glass Co. Ltd., Tokyo, Japan). The solution was agitated continuously at 400 rpm with a magnetic stirrer (SRS710DA, Advantec Toyo Kaisha, Ltd., Tokyo, Japan) attached on the bottom surface of the reactor. The removal experiments were performed in Milli-Q water which contain each pharmaceutical of 500 ng/L, the values of which was previously determined based on the average of concentrations found in WWTPs and hospital effluents (10 ng/L to several g/L) [33, 34]. Ultra-performance LC–tandem MS (UPLC–MS/MS) was used for estimation of concentration of each pharmaceutical to ensure sensitivity of detection of removal efficiency after pretreatment by solid-phase extraction (SPE) as described in Section 2.3. O3 was generated by an ozone generator (ED-OG-R6, Ecodesign Inc., Saitama, Japan). and injected continuously into the reactor at a flow rate of 0.3 L/min and a concentration at 6.5 mg/L, corresponding to a feed rate of 1.0 mg/L/min. This feed rate was the same as the one used in WWTPs (6 mg/L for 20 min) [35] and previous studies of the removal of pharmaceuticals by ozonation [36, 37]. For the O3-MB treatments, O3 was introduced inside of a microbubble generator by a pump with a circulation volume of 1 L/min. Pressure at 20 kPa was used to generate microbubbles having a modal pore diameter of 33 m (Fig. S2). The O3 consumption was calculated from the balance in both gas and liquid phases during the experiment [22, 38]. UV irradiation was supplied by a 9-W low-pressure mercury lamp (TCGU60-250ZP, Miyakawa Corp., Tokyo, Japan) with a peak wavelength of 254 nm and an intensity of 2.8 mW/cm2 as used in the previous studies [39]. The UV lamp was introduced into the reactor
6
and kept separate from the water by a quartz jacket. The initial H2O2 concentration was set at 5 mg/L, as in previous studies [40]. A portion of the reactor solution (160 mL, 4 × 40 mL) was sampled at 0, 2, 5, 10, 20 and 30 min after the experiment, while at 0, 1, 2, 3, 5 and 10 min in the O3-MB experiments, respectively, for measurement of concentrations. Duration of the reaction was changed by reflecting the average contact time in actual WWTPs that use ozonation before discharge into rivers in Japan (15 ± 5 min) [35], and the values reported in the previous reports [36, 37]. Ascorbic acid was immediately added to each sample to a final concentration of 1.0 g/L to remove residual O3 and hydrogen peroxide and to quench reactive oxygen species such as OH·, guaranteeing the end of the oxidation reactions [41]. The samples were then stored at 4 °C in dark and processed within 24 h. Each solution was pretreated by SPE or ultrasonic extraction and analyzed by UPLC-MS/MS as described in Section 2.3.
2.3 Analytical procedures SPE and UPLC–MS/MS were used for all analyses as previously described [42]. In brief, four 40-mL aliquots were taken for analysis of each sample and filtered separately through a glass fiber filter (GF/B, 1-m pore size, Whatman, Maidstone, UK). Four SPE cartridges (Oasis HLB, 200 mg; Waters Corp., Milford, MA, USA) were preconditioned for each sample by washing first with 3 mL methanol and then with 3 mL Milli-Q water adjusted to pH 3 with 1 N HCl. A known amount of each compound was spiked into two aliquots for analysis to a final concentration of 500 ng/L. The spiked aliquots were then applied to two different SPE cartridges at 1 mL/min. Similarly, unspiked aliquots were applied to the remaining two cartridges. All cartridges were washed with 6 mL Milli-Q water adjusted to pH 3 and then dried by vacuum pump. Finally, the adsorbed pharmaceuticals were eluted in a stepwise manner with 3 mL acetone + 3 mL methanol, 2 mL 10% (v/v) formic acid in acetone, 2 mL
7
10% (v/v) formic acid in methanol, and finally 2 mL 5% ammonia–methanol (v/v). Each combined eluate solution was evaporated to dryness under a gentle stream of nitrogen gas at 37 °C. The residue was solubilized in 200 L of a 90:10 (v/v) mixture of 0.1% formic acid solution in methanol, and 10 L of this solution was analyzed by UPLC-MS/MS on a reverse-phase UPLC device fitted with a UPLC BEH C18 column (2.1 mm × 100 mm, 1.7 m; Waters Acquity, Waters Corp.). For simultaneous analysis of the target compounds, a gradient elution program was used at 60 °C with a solvent mix of 0.1% formic acid (v/v) in Milli-Q water (A) and methanol (B) at a flow rate of 0.35 mL/min under a program of 0.0 to 2.0 min (10% B), 2.0 to 8.0 min (25% B), 8.0 to 14.0 min (55% B), 14.0 to 16.0 min (55% B), 16.0 to 19.0 min (90% B), 19.0 to 19.2 min (100% B), 19.2 to 21.2 min (100% B), 21.2 to 24.0 min (10% B), and 24.0 to 26.0 min (10% B). The UPLC system was coupled to a TQD tandem quadrupole mass spectrometer (Waters Corp.) equipped with an electrospray ionization source and operated both in positive and negative ion modes. The samples were analyzed by time-scheduled acquisition for multiple reaction monitoring based on the combination of precursor and product ions. Detailed information on the analytical parameters used for LC-MS/MS is given in Table S2.
2.4 Method validation Six-point standard calibration curves were constructed for quantification at a concentration range from 0.5 to 200 ng/mL. The individual linear calibration curves for each compound were obtained (r2 > 0.99) by selecting a weighting factor of 1/x. The blank data were subtracted from the spiked sample data to account for matrix effects and loss during sample extraction [32]. Recovery rates were calculated from the deviations between the spiked data and the standard data; values ranged from 60% to 110%, generally similar to those reported in previous studies of pharmaceuticals in river and sewage samples [33, 43]. The limits of
8
detection and of quantification were calculated as the concentrations at signal-to-noise ratios of 3 and 10, respectively, according to methods used for pharmaceuticals [43].
3. Results and discussion 3.1 Enhancement of removal rates To show the aim of the present study clearly, the results were explained from the standard O3 treatments. Treatments with O3 removed >90% of 26 compounds within 5 min (Fig. 1). These results are similar to previous results [14, 17, 18]. Some compounds were, however, fairly resistant: removal rares of bortezomib acid (48%), loxoprofen (48%), bicalutamide (43%), cyclophosphamide (22%) and acetaminophen glucuronide (19%). These compounds were classified as gradually degradable by ozonation. The pharmaceuticals in the class of contrast media were resistant to highly resistant iohexol (35%), ioversol (33%), iopromide (9%), iomeprol (6%) and iopamidol (0%). This high recalcitrance of contrast media to ozonation is similar to the removal rates (10% to 42%) reported previously [23, 44, 45]. Combined treatments of O3 with UV and UV/H2O2 were found to improve these low removal rates. In particular, combined treatments with O3/UV and O3/UV/H2O2 greatly improved the removal of bortezomib acid (83%–100%), iohexol (99%), ioversol (93%–97%), iopromide (94%–98%), iomeprol (96%–99%), and iopamidol (95%–97%). In contrast, increment of reaction rate by O3/H2O2 was as low as 0%–36%. These results indicate that the main improvement in O3/UV and O3/UV/H2O2 is due to direct photolysis by UV, meaning participation of OH· generated by combined use of O3 and UV as described previously [46]. This interpretation is supported further by the results that the contrast media type compounds absorb energy mainly in the region of 220–280 nm [47], and that their half-lives under UV were only 0.5 min for iohexol [47], 0.2–6 min for iopamidol [47, 48], and 0.5 min for iopromide [47].
9
The present new technique joining O3 with MB opened a new approach to remove vast kinds of pharmaceuticals. Namely, O3-MB increased removal rates by 8%–34% compared with O3 alone, and could remove >90% of 26 to 32 compounds (Table 1). O3-MB also enhanced the removal of the recalcitrant compounds against O 3: acetaminophen glucuronide (32% from 19%), bortezomib acid (88% from 48%), and loxoprofen (82% from 48%). Combined use of UV (O3-MB/UV) further improved the removal rate of acetaminophen glucuronide to 80% and all compounds belong to contrast media as previously observed in O3/UV and O3/UV/H2O2. It must be stressed that combined use of UV and H2O2 (O3MB/UV/H2O2) alone enhanced the removal rate of famciclovir and bicalutamide to attain 96% and 99%, respectively, together with complete removal of bortezomib acid. Combined use of H2O2 (O3-MB/H2O2) was effective similar to O3-MB/UV/H2O2, but did not have a power enough to remove famciclovir and contrast media type compounds. MB treatment was concluded to be essential for removal of famciclovir, bicalutamide, sulpiride, acetaminophen glucuronide and loxoprofen. Removal efficiencies were estimated as 81% ± 31% (mean ± SD) by O3-MB, 90% ± 19% by O3-MB/UV, 85% ± 24% by O3-MB/H2O2, and 94% ± 15% by O3-MB/UV/H2O2. On account of the remained two compounds, cyclophosphamide and acetaminophen sulfate whose removal rates were still low (32% for the former and 74% for the latter), we are waiting for appearance of new technologies which will overcome their recalcitrance. The present analytical results also indicate that the amounts of dissolved organic carbon (DOC) did not change before and after the present experiments, in accord with the previous results which showed remaining of the degraded products as stable compounds such as in the form of organic acids [49, 50].
Further investigation seems necessary in relation to
degradation mechanisms with characterization of chemical structure of the reaction products [51, 52] and their impact on the environment and organisms [53, 54].
10
Table 1. Efficiency of removal of target pharmaceuticals during 5-min O3 treatment: O3 based treatment system and O3-MB based treatment system. Removal rate (%) O3 based treatment system
O3-MB based treatment system
Therapeutic Compound
O3 -
class O3
Aciclovir
O3/UV
O3/H2O2
O3
O3 -
/UV/H2O2
MB
MB/ UV
O3-MB
O3-MB/UV/
/H2O2
H2 O2
100.0
99.6
100.0
98.1
100.0
100.0
100.0
100.0
63.3
31.0
22.1
19.2
66.1
65.8
78.9
96.0
Penciclovir
100.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
Cefdinir
100.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
76.7
98.4
48.4
100.0
99.0
90.1
98.5
94.8
79.6
45.5
60.2
100.0
96.5
87.0
99.4
Levofloxacin
100.0
98.5
100.0
70.5
100.0
99.6
99.8
100.0
Bicalutamide
42.9
47.6
39.2
15.4
38.7
35.3
10.3
98.9
100.0
97.8
72.7
99.9
62.7
71.2
98.5
99.3
Bortezomib acid
48.4
100.0
64.2
82.6
87.8
58.8
100.0
100.0
Capecitabine
99.5
97.3
97.1
85.0
100.0
100.0
100.0
100.0
21.5
0.0
13.9
12.0
14.0
30.2
26.1
32.0
99.9
99.0
100.0
97.1
100.0
100.0
100.0
100.0
Famciclovir
Anti-viral
Ciprofloxacin Anti-bacterial Clarithromycin
Bortezomib
Cyclophosphamide Anti-cancer Doxifluridine Etoposide
100.0
99.9
99.5
100.0
100.0
100.0
100.0
100.0
Tamoxifen
100.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
4-Hydroxy tamoxifen
100.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
Tegafur
100.0
100.0
100.0
94.0
100.0
100.0
100.0
100.0
99.9
100.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
3-Hydroxy carbamazepine
99.4
95.2
100.0
100.0
100.0
100.0
100.0
100.0
Sulpiride
85.4
32.8
67.4
39.7
98.6
80.3
92.7
82.1
Losartan
100.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
99.9
97.3
100.0
95.1
100.0
99.9
99.7
100.0
Olmesartan medoxomil
99.8
97.1
99.2
63.2
100.0
99.8
100.0
100.0
Acetaminophen
99.9
91.0
100.0
95.2
99.8
98.7
98.5
94.4
Carbamazepine 2-Hydroxy carbamazepine Psychotropic
Losartan carboxylic acid
Anti-
Olmesartan
hypertensive
Acetaminophen glucuronide
Analgesic-
19.2
52.0
26.6
16.9
31.9
80.2
84.2
100.0
Acetaminophen sulfate
antipyretic
60.8
73.5
37.0
65.8
53.5
42.8
64.5
34.7
Loxoprofen
47.5
63.6
0.0
14.4
81.6
67.7
70.2
78.0
Iohexol
34.8
98.8
0.0
98.5
52.0
98.3
60.8
99.9
5.6
99.1
0.0
95.8
30.9
94.9
44.4
94.6
0.0
94.8
0.0
97.2
0.0
96.2
39.2
89.5
Iomeprol Iopamidol
Contrast media
Iopromide Ioversol Caffeine
8.6
94.1
45.3
98.0
44.5
97.6
60.4
87.8
33.1
97.0
0.0
93.3
11.6
93.8
34.6
85.4
95.9
53.6
93.9
27.0
97.5
97.0
91.2
93.5
100.0
99.8
98.4
74.6
100.0
99.7
99.9
98.8
100.0
100.0
100.0
99.4
100.0
100.0
100.0
100.0
100.0
100.0
100.0
99.0
100.0
100.0
100.0
100.0
100.0
100.0
100.0
99.9
100.0
100.0
100.0
100.0
Bronchodilator Theophylline Crotamiton
Anti-pruritic
Berberine Herbal medicine Puerarin
11
3.2 Reaction kinetics and distribution of reaction rate constant Figure 1 shows the removal of doxifluridine (a representative compound immediately removed by O3) and sulpiride (relatively rapidly removed by O3). The reactions followed pseudo-first-order kinetics (r2 > 0.90), as previously reported [55]. Table 2 shows the distribution of reaction rate constant for all compounds grouped in 10 therapeutic classes. The reaction rate constants differed between O3 and O3-MB treatments (P < 0.01 (Fig. S3)). Under O3 treatments, values were 1.1 ± 1.1 min−1 by O3, 1.0 ± 0.9 min−1 by O3/UV, 1.1 ± 1.2 min−1 by O3/H2O2, and 0.8 ± 0.8 min−1 by O3/UV/H2O2. Under O3-MB treatments, on the other hand, 2 to 7-fold increase in the values were observed: 2.5 ± 2.4 min−1 by O3-MB, 2.0 ± 2.1 min−1 by O3-MB/UV, 2.2 ± 2.2 min−1 by O3-MB/H2O2, and 3.0 ± 2.5 min−1 by O3MB/UV/H2O2. These results support to conclude that the O3-MB treatment is more effective than the conventional O3 treatment. The reaction rate constants differed also among pharmaceutical classes. Both O3 and O3MB treatments rapidly removed all antihypertensives (0.4–6.6 min−1; half-lives of 0.1–2.0 min) and herbal medicines (0.9–6.8 min−1 ; half-lives of 0.1–0.8 min). However, the rate constants of the other class-pharamaceuticals varied widely: 0.04 to 4.9 min−1 for antivirals, 0.09 to 6.0 min−1 for antibacterials, 0.001 to 7.3 min−1 for anticancer drugs, 0.08 to 6.3 min−1 for psychotropics, 0.01 to 1.7 min−1 for analgesic-antipyretics, 0.001 to 1.0 min−1 for contrast media, and 0.08 to 6.6 min−1 for bronchodilators. In the cases for the combined treatments including UV, O3/UV, O3/UV/H2O2, O3-MB/UV and O3-MB/UV/H2O2 photolysis was thought to play a key role in the observed significant enhancement of the removal of bortezomib acid, iohexol, iomeprol, iopamidol, iopromide, and ioversol for 2.3–332 times relative to O3 and O3-MB [56] (see Section 3.1). On the next step, any new devices which permit real time characterization of correlation between chemical structure and removal rate [57, 58] are to be introduced in future for further enhancement of
12
the efficiency of the present treatment system. Reaction time (min) 0 0
0
Reaction time (min)
2
4
2
6
4
6
8
10
8
10
0
(1)
O3
O O33 O3/UV
-2 Ln (C/C0)
Ln (C/C0)
O3/UV O 3/UV
O3/H2O2
O3/H2O2 O 3/H2O2
-2
O3/UV/H2O2
O3/UV/H2O2 O 3/UV/H2O2
-4 -4
MB-O3 MB-O3 O 3-MB MB-O3/UV O MB-O3/UV 3-MB/UV
-6 -6
MB-O3/H2O2 O -MB/H2O2 3MB-O3/H2O2
O -MB/UV/H2O2 MB-O3/UV/H2O2 3MB-O3/UV/H2O2
-8 -8
線形 (O3) 線形 (O3)
Reaction time (min) 0
2 0
-2 Ln (C/C0)
Ln (C/C0)
0
Reaction time (min)
4
2
6
4
6
線形 (O3/UV)
線形 (O3/UV)
8
10
8
10
0
線形 (O3/H2O2)
線形 (O3/H2O2)
O3 線形 O O33線形 (O3/UV/H2O2) O3/UV (O3/UV/H2O2) 線形 (MB-O3) O /UV (MB-O3) O3/UV 3線形 線形 (MB-O3/UV) O3/H2O2
O3/H2O2 O /H2O(MB-O3/UV) 3線形 2
-2
線形 (MBO3/UV/H2O2
O3/UV/H2O2 O 3/UV/H2O2 O3/H2O2)
線形 (MB-
線形 (MB-
-4 -4
MB-O3 O3/H2O2) O MB-O3 3-MB O3/UV/H2O2) 線形 (MB-
MB-O3/UV O3/UV/H2O2) O MB-O3/UV 3-MB/UV
-6 -6
MB-O3/H2O2 MB-O3/H2O2 O 3-MB/H2O2
(2)
MB-O3/UV/H2O2 O MB-O3/UV/H2O2 3-MB/UV/H2O2
-8 -8
線形 (O3) 線形 (O3) 線形 (O3/UV)
線形 (O3/UV) Figure 2. Relative residual concentrations of pharmaceuticals (C0, initial concentration; 線形 (O3/H2O2)
C, concentration after reaction): (1) doxifluridine, (2) sulpiride.
線形 (O3/H2O2)
線形 線形 (O3/UV/H2O2) (O3/UV/H2O2) 線形 (MB-O3)
線形 (MB-O3)
線形 (MB-O3/UV)
線形 (MB-O3/UV) 線形 (MBO3/H2O2) 線形 (MB線形 (MBO3/H2O2) O3/UV/H2O2) 線形 (MB-
O3/UV/H2O2)
13
Table 2. First-order rate constants of target pharmaceuticals by using O3 and O3-MB based water treatment systems. Reaction rate (min-1) Therapeutic
O3-based treatment system
Compound class
O3-MB based treatment system O3 -
O3 -
O3 -
O3 -
MB
MB/UV
MB/H2O2
MB/UV/H2O2
3.068
3.258
3.714
0.185
0.215
0.267
0.513
1.106
4.007
2.724
4.820
4.875
1.362
1.320
6.016
5.724
5.981
4.920
0.178
0.778
0.148
2.325
0.698
0.492
0.747
0.541
0.273
0.087
0.173
2.504
0.698
0.445
1.050
2.205
0.617
2.645
0.242
2.615
1.157
1.393
2.294
Bicalutamide
0.037
0.109
0.019
0.015
0.143
0.073
0.078
0.912
Bortezomib
0.001
0.704
0.544
1.387
0.104
0.272
0.652
0.856
Bortezomib acid
0.194
1.548
0.116
0.792
0.280
0.190
5.334
2.241
Capecitabine
1.024
0.683
0.685
0.228
3.055
2.562
2.471
4.180
Cyclophosphamide
0.020
0.022
0.014
0.048
0.021
0.048
0.053
0.080
Doxifluridine
1.399
0.897
2.029
0.674
5.100
1.991
2.462
5.318
Etoposide
1.797
1.349
1.066
2.389
3.864
3.364
5.616
6.254
Tamoxifen
1.151
0.896
0.693
0.693
0.693
6.109
5.991
6.477
4-Hydroxy tamoxifen
1.099
0.973
0.896
1.151
1.099
1.194
2.639
2.639
Tegafur
2.097
3.129
2.772
0.638
7.281
3.306
3.188
6.845
Carbamazepine
1.943
1.640
1.680
1.894
6.314
6.268
5.554
5.305
2.913
2.642
3.883
4.158
4.135
6.225
2.317
5.613
3-Hydroxy carbamazepine
0.909
0.383
3.809
1.704
4.871
6.048
6.281
4.950
Sulpiride
0.195
0.082
0.157
0.086
0.652
0.320
0.372
0.373
Losartan
2.394
2.534
2.272
1.857
5.451
2.768
5.971
5.609
O3
O3/UV
O3/H2O2
1.320
1.128
1.782
0.772
2.944
0.114
0.042
0.082
0.063
Penciclovir
2.102
2.087
2.233
Cefdinir
2.617
2.639
0.276
Clarithromycin Levofloxacin
Aciclovir Famciclovir
Anti-viral
Ciprofloxacin
O3/UV/H2O2
Anti-bacterial
Anti-cancer
2-Hydroxy carbamazepine Psychotropic
Losartan carboxylic acid
Anti-
1.684
1.557
1.242
0.723
3.332
1.789
3.033
6.593
Olmesartan
hypertensive
1.389
0.758
2.471
0.350
3.336
1.315
1.271
6.342
Olmesartan medoxomil
1.333
0.665
0.876
0.431
1.518
1.280
2.183
2.186
Acetaminophen
1.527
0.658
1.676
0.671
1.302
0.671
0.613
0.452
Acetaminophen glucuronide
Analgesic-
0.102
0.108
0.110
0.071
0.137
0.274
0.348
1.493
Acetaminophen sulfate
antipyretic
0.064
0.118
0.122
0.288
0.108
0.084
0.163
0.092
Loxoprofen
0.043
0.216
0.012
0.158
0.358
0.282
0.165
0.449
Iohexol
0.039
0.823
0.031
0.599
0.109
0.734
0.587
1.027
0.015
0.849
0.042
0.314
0.039
0.651
0.089
0.635
0.001
0.591
0.016
0.635
0.008
0.561
0.312
0.573
Iopromide
0.030
0.491
0.039
0.678
0.082
0.594
0.117
0.581
Ioversol
0.028
0.658
0.013
0.452
0.017
0.507
0.059
0.513
Caffeine
0.148
0.099
0.242
0.082
0.541
0.438
0.347
0.393
2.698
1.244
0.710
0.179
6.554
1.035
1.377
0.682
Iomeprol Contrast Iopamidol media
Bronchodilator Theophylline Crotamiton
Anti-pruritic
2.957
2.436
2.602
2.079
5.663
5.808
5.771
5.198
Berberine
Herbal
2.794
1.901
1.688
0.920
4.052
5.412
2.235
6.613
Puerarin
medicine
3.409
2.110
3.153
1.547
6.817
3.328
3.181
6.475
14
3.3 Efficiency of O3-MB treatment based on O3 consumption The O3-MB based treatments consumed up to 2.8-fold O3 than the O3 treatments (Fig. 2). Mean improvements were 2.0 ± 0.6 times by O3-MB, 1.0 ± 0.1 times by O3-MB/UV, 2.8 ± 0.2 times by O3MB/H2O2, and 1.3 ± 0.1 times by O3-MB/UV/H2O2. These results agreed with the distribution of reaction rate constants as shown in Table 2. The removal rates increased as effective usage of O3 increased, although any significant correlation was not obserbed. Difficulty in characterization of the reaction rate constants was in that HO· has a higher oxidation potential (2.8 V) than ozone (2.1 V) [59], and thus will immediately react with O3 as strong quenching agents [60] together with its consumption due to unknown secondary reactions in water. Because of these side reactions, not all of the HO·contributed to the degradation of the test compounds [60, 61].
Ozone consumption (mg/L)
Ozone consumption (mg/L)
y = 0.434 x
O3 O3 O3 O3/UV
12 12
O3/H2O2 O3/UV O3/UV O3/UV/H2O2 MB-O3 O3/H2O2 O3/H2O2 MB-O3/UV MB-O3/H2O2 O3/UV/H2O2 O3/UV/H2O2 MB-O3/UV/H2O2 MB-O3 O3-MB 線形 (MB-O3/H2O2)
9 9 6
6 3
3 0 0
0 0
2
2
4
6
8
4 6 (min) 8 Reaction time
10
R2 = 0.953 y = 0.694 x R2 = 0.999 y = 0.445 x R2 = 0.985 y = 0.915 x R2 = 0.995
線形 (MB-O3/UV/H2O2) MB-O3/UV O -MB/UV 線形3 (MB-O3) 線形 (O3/UV/H2O2) y = 1.046 x MB-O3/H2O2 O3-MB/H 2O2 線形 (O3/UV) R2 = 0.996 線形 (O3) MB-O3/UV/H2O2 O3-MB/UV/H O 2 2 y = 0.712 x 線形 (O3/H2O2) R2 = 0.995 線形 (MB-O3/UV)
10
Reaction time (min)
y = 1.256 x R2 = 0.997 y = 1.163 x R2 = 1.000
Figure 2. Ozone consumption over time in each treatment system. Wastewater treatment using O3-MB has advantages. First, O3-MB treatment can reduce energy costs by enhancing O3 consumption relative to conventional O3 treatment, in which O3 diffuses quickly out of the liquid phase [20]. Second, although catalysts such as UV and H2O2 can improve efficiency, they are not essential for 15
O3-MB treatment. These advantages are effective not only for reducing the discharge of pharmaceuticals into the environment (environmentally friendly systems), but also in the construction and management of wastewater treatment plants [22, 23]. Research to develop O3-MB is expanding rapidly worldwide. In addition to environmental uses such as water purification and wastewater treatment, O3-MB can expect to find uses in agriculture for washing vegetables [30, 62] and in health for the disinfection of medical apparatus [63], and in treating hospital effluent [10, 64]). Our findings should be of value in developing new advanced water treatment systems to minimize the discharge of pharmaceuticals into rivers.
4. Conclusions Removal rates of 39 pharmaceuticals in 10 therapeutic classes (antivirals, antibacterials, anticancer drugs, psychotropics, antihypertensives, analgesic-antipyretics, contrast media, bronchodilators, antipruritics, and herbal medicines) in water were estimated by introduction of O3-MB, and the results were compared with those given by O3 alone and combined treatments with UV, and/or H2O2, or both. The results indicated that degradability of the O3-MB treatment enhanced removal rates by 8%–34% compared with O3 (P < 0.01) and 90% degradability was attained for 33 compounds (˃80% for 37 compounds). MB technology was indispensable to remove ˃90% of famciclovir (anti-viral), bicalutamide (anti-cancer), sulpiride (phychotropic) and acetaminophen glucuronide (analgesic-antipyretic). Recalcitrant properties of all contrast media type pharmaceuticals (iohexol, ioversol, iopromide, iomeprol and iopamidol) disappeared by combined treatment with UV, and removal rates became 94%-99% from 0%-52%. Combined use of UV (O3-MB/UV and O3MB/UV/H2O2) enhanced the reaction rate constants by 2.9–5.5 times in average relative to O3 and O3-MB. 16
Ozone consumption in O3-MB was up to 2.8 times higher than that in the O3 treatment. The results indicate that O3-MB as a new advanced water treatment system would minimize the discharge of pharmaceuticals into river environments.
Acknowledgments We acknowledge the Sumitomo Foundation (153018), Kurita Water and Environment Foundation (14E007), Maeda Engineering Foundation, and the Ministry of Education, Culture, Sports, Science and Technology of Japan (16K16218) for funding in the form of research grants and scholarships. We also thank the Promoting Academic Exchange Board of the Osaka University of Pharmaceutical Sciences for supporting our collaborative studies.
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25
Highlights
O3-MB was applied to remove 39 pharmaceuticals in 10 therapeutic classes in water. Over 90% removal rate was obtained for 33 compounds (>80% for 37 compounds). O3-MB enhanced removal efficiency by 8%–34% relative to the conventional O3. UV and/or H2O2 increased the reaction rate constant by 2.9–5.5 times relative to O3-MB. MB treatment improved O3 consumption up to 2.8 times higher than O3 treatments.
26
Graphical Abstract
Pharmaceuticals
OzoneMicrobubble O3-MB, O3-MB/UV, O3-MB/H2O2, O3-MB/UV/H2O2
0 25 50
27
1 0 0 1 5 0 ( m)