Photochemical transformation of flufenamic acid by artificial sunlight in aqueous solutions

Article abstract of DOI:10.1016/j.jphotochem.2015.10.003

In the present article, we have studied the photochemical behavior of a common non-steroidal anti-inflammatory drug (NSAIDs) namely flufenamic acid (FLUA) in aqueous solution. The absorption spectrum of such compound shows a significant absorption beyond

Full text of DOI:10.1016/j.jphotochem.2015.10.003

Journal of Photochemistry and Photobiology A: Chemistry 316 (2016) 1–6
Contents lists available at ScienceDirect
Journal of Photochemistry and Photobiology A:
Chemistry
journal homepage: www.elsevier.com/locate/jphotochem
Photochemical transformation of flufenamic acid by artificial sunlight
in aqueous solutions
b,c
Salah Rafqaha, , Mohamed Sarakha
*
a
Equipe de Chimie Analytique et Environnement (ECAE), Département de Chimie, Faculté Polydisciplinaire de Safi, Université Cadi Ayyad, B.P. 4162, 46000
Safi, Morocco
b
Clermont Université, Université Blaise Pascal, Institut de Chimie de Clermont-Ferrand, Equipe Photochimie, BP 10448, F-63000 Clermont Ferrand, France
CNRS, UMR 6296, ICCF, Photochimie, BP 80026, F-63171 Aubière, France
c
A R T I C L E I N F O
A B S T R A C T
Article history:
Received 22 June 2015
Received in revised form 25 September 2015
Accepted 3 October 2015
Available online 8 October 2015
In the present article, we have studied the photochemical behavior of a common non-steroidal anti-
inflammatory drug (NSAIDs) namely flufenamic acid (FLUA) in aqueous solution. The absorption
spectrum of such compound shows a significant absorption beyond 290 nm and the photochemical
irradiation within the range 300–450 nm leads to its complete transformation in roughly 6 h. The
quantum yield of FLUA transformation measured at 290 and 310 nm was evaluated to about 1.1 ꢀ10ꢁ4
without any significant effect of the excitation wavelength. The degradation process was inhibited in
acidic solutions owing to the sharp increment in the absorption of FLUA in the wavelength region
between 300 and 350 nm. The quantum yield was estimated to 1.2 ꢀ10ꢁ4 at pH 7. The effect of oxygen on
the photochemical behavior of FLUA has also been investigated. The obtained results clearly indicate that
oxygen is not significantly involved in the photochemical degradation process. The phototransformation
of the flufenamic acid appears to occur through one pathway that involves the photohydrolysis of
trifluoromethyl group, and thus leads to the formation of one specific photoproduct, namely 2,30-imino-
dibenzoic acid. This result was confirmed by the formation of the fluoride ions after irradiation during the
irradiation of flufenamic acid. A mechanistic scheme for such transformation of flufenamic acid was
proposed.
Keywords:
Flufenamic acid
Phototransfomation
Aqueous solution
Non-steroidal anti-inflammatory
Photohydrolysis
ã 2015 Elsevier B.V. All rights reserved.
1. Introduction
considered as potential degradation routes of their transformation
in surface waters [8]. Exposure to sunlight has already been
Many pharmaceutical compounds used as human and veteri-
nary drugs pass, at least in part, through sewage treatment plants
(SWT) to end up in environmental natural waters. They are
suspected to reach every environmental compartment. Indeed, it
has been frequently reported that they have been detected in lakes,
groundwater, and also in drinking water [1–5]. It has been largely
reported that biodegradation and photodegradation are among
major transformation processes influencing the fate of such
pollutants in natural waters. However, Biological processes can
confirmed as one of the most important way of their transforma-
tion in natural aquatic environments [9–11]. However, the
photochemical transformation process efficiency in surface waters
is dependent on various environmental factors such as the depth,
turbidity, geographic latitude, season, weather and shadow [12].
Non-steroidal anti-inflammatory drugs (NSAIDs) are a group of
drugs of diverse chemical composition and most often used in
human and veterinary medicine, since they are available without
prescription for treatment of fever and minor pains [13]. Many
NSAIDs have been found or are expected to be present in the
aquatic environment at significant concentrations [14–16]. In
addition, this family compounds showed a remarkable reactivity
toward the light. Indeed, they rapidly react under irradiation and
can be largely eliminated from surface waters, owing to photolysis
reactions. Direct photolysis by sunlight or artificial light constitutes
the dominant degradation mechanism and the removal process for
these products [17–20].
induce
a limited degree of transformation because of the
biopersistence of many organic compounds as well as their
generated byproducts that result from the incomplete biodegra-
dation [6,7].
Since several pharmaceutical compounds are usually resistant
to biodegradation, either direct or indirect photolysis may be
N-(
a,a,a-trifluoro-m-tolyl) anthranilic acid known as flufe-
* Corresponding author.
E-mail address: rafqah2004@yahoo.fr (S. Rafqah).
namic acid (FLUA) is a common non-steroidal anti-inflammatory
http://dx.doi.org/10.1016/j.jphotochem.2015.10.003
1010-6030/ã 2015 Elsevier B.V. All rights reserved.

2
S. Rafqah, M. Sarakha / Journal of Photochemistry and Photobiology A: Chemistry 316 (2016) 1–6
drugs (NSAIDs) that belongs to the family of N-phenylanthranilic
acid and resembles chemically to mefenamic and tolfenamic acids
and other fenamates that are largely used in clinical issues [21].
flufenamic acid presents analgesic, anti-inflammatory and antipy-
retic properties and has been used in musculoskeletal as well as
joint disorders [22].
FLUA is often found in the environment at significant
concentrations [16]. The presence of mixtures of flufenamic and
mefenamic acids in human urine samples in relatively important
concentrations has also been demonstrated [23,24]. A very recent
study also revealed the presence of flufenamic acid at considerable
concentration, in rivers water [16]. Until now, however, there is
very limited information concerning the photochemical behavior
of flufenamic acid in aqueous solutions. In the present paper, we
report results of its photochemical behavior from kinetic as well as
analytical points of view. Our approach includes the selection of
appropriate conditions in order to obtain the best results and to
evaluate the effect of environmental parameters on the photolysis
efficiency of flufenamic acid.
2.3. Analysis
The disappearance of FLUA and the formation of the byproducts
were followed by HPLC technique that consists on a Waters
540HPLC chromatograph system equipped with a Waters 996 pho-
todiode array detector. The chromatograms were extracted at
288 nm as detection wavelength. The separation of the solutions
components was accomplished by using a reverse phase Nucleodur
column (C18–5
and the injected volume was set to 50
m
m; 250–4.6 mm). The flow rate was 1.0 mL/min
L. The elution was
m
accomplished with water that was acidified with formic acid (0.1%)
and acetonitrile using an isocratic program (60% water and 40%
acetonitrile).
The quantum yield of FLUA disappearance was measured at
290 and 310 nm by using the following expression:
F= number of
decomposed molecules of pollutant/number of photons absorbed
by pollutant.
LC/MS studies were carried out with Q-TOF-Micro/water
2699 from UBSTART center at the University Blaise Pascal. It is
equipped with an electrospray ionization source (ESI) and a Waters
photodiode array detector. Each single experiment permitted the
simultaneous recording of both UV chromatogram at a preselected
wavelength and an ESIMS full scan. Data acquisition and
processing were performed by MassLynx NT 4.0 system.
The evolution of fluoride ions concentration as a function of
irradiation time was obtained by ionic chromatography (IC) using a
Dionex ICS-1500 equipped with an ionPac CG16 (analytical column
5 ꢀ 250 mm).
2. Materials and methods
2.1. Chemical and reagents
The “N-(a,a,a-trifluoro-m-tolyl) anthranilic acid” known as
flufenamic acid (FLUA) was purchased from Fluka and used
without any further purification. 2,30-imino-dibenzoic acid was
obtained from Alfa Chemistry as the purest grade available.
Acetonitrile was purchased from Carlo Erba (HPLC grade). All
solutions were prepared with deionized ultrapure water, which
was purified with Milli-Q device (Millipore) and its purity was
UV–vis spectra were recorded on a Cary 300 scan (Varian)
spectrophotometer.
controlled by its resistivity (>18 M
V
cm). The measurements of pH
3. Results and discussion
were undertaken using a JENWAY 3310 pH-meter to ꢂ0.01 pH unit
and the ionic strength was not controlled during the irradiation
experiments. The pH of the solutions was adjusted using dilute
solutions of HClO4 or NaOH.
Solutions were deoxygenated by nitrogen bubbling or oxygen-
ated by oxygen bubbling for 30 min prior to irradiation at room
temperature. For prolonged irradiations, the bubbling was main-
tained during the entire irradiation process.
3.1. Spectrophotometric study
The absorption spectrum of flufenamic acid at a concentration
of 5.0 ꢀ10ꢁ5 mol Lꢁ1 in aqueous solution and at pH of 5.6 exhibits a
band with a maximum at 288 nm (e
288 = 19,400 molꢁ1 L cmꢁ1) and
a shoulder at about 325 nm (
conditions, namely a pH 2.1, the absorption spectrum consisted of
two well-defined bands at 283 nm (
283 = 6500 molꢁ1 L cmꢁ1) and
345 nm (
345 = 3650 molꢁ1 L cmꢁ1). It is worth noting that
significant absorption at > 300 nm is observed (Fig. 1), which
e
325 = 8800 molꢁ1 L cmꢁ1). For acidic
e
2.2. Irradiation systems
e
a
l
For kinetic purposes, aqueous solutions were irradiated in a
quartz cell (1 cm optical path length) using an arc Xenon lamp
from OSRAM (XBO 1600 W/XL OFR). The emission of the lamp
extends from 270 nm to 850 nm with a maximum at 650 nm. The
entire system is equipped with a Schoeffel monochromator to
select the appropriate wavelengths for monochromatic irradi-
ations. Two different wavelengths were used: 290 nm and
310 nm. The bandwidth was set to 10 nm. The initial concentra-
tion of the solution was checked by HPLC analysis after oxygen or
nitrogen bubbling. Potassium ferrioxalate was used as a chemical
actinometer [25]. The light intensity was found equal to 1.5 ꢀ1015
photons cmꢁ2 sꢁ1 and 2.2 ꢀ1015 photons cmꢁ2 sꢁ1 at 290 nm
and 310 nm respectively. By modifying the bandwidth modified
the light intensity changes. For analyses purposes, excitations
within the range 300–450 nm were performed. The irradiation
device consists of a vertical Pyrex tube (20 mm internal diameter
with a total volume of 100 mL) equipped with a water cooling
jacket to limit thermal reactions. It is located along one of the
focal axes of a cylindrical mirror with an elliptic base. A
fluorescent lamp TLD15 W/05 emitting within the range 300–
450 nm is located along the other focal axis. The distance
between the lamp and the reactor was constant and equal to
approximately 13 cm.
indicates a significant overlaps with the emission spectrum of the
solar radiation that reaches the biosphere.
0,4
1,5
pH = 5.6
1,0
0,2
solar emission
pH = 2.1
0,5
0,0
200
0,0
300
400
Wavelength, nm
Fig. 1. Characteristic UV spectra of FLUA (2.0 ꢀ10ꢁ5 mol Lꢁ1) at pH 5.6 and pH 2.1 in
aqueous solution compared to the solar emission spectrum.

S. Rafqah, M. Sarakha / Journal of Photochemistry and Photobiology A: Chemistry 316 (2016) 1–6
3
0,8
0,6
0,4
0,2
0,0
1.0
(a)
(b)
1,0
0,8
0,6
0,4
0,2
0,0
initial
1h
oxygen saturated solution
aerated solution
0.8
0.6
0.4
0.2
0.0
2h
deoxygenated solution
4h
6h
0
1
2
3
4
5
6
Irradiation time, hours
250
300
350
400
450
λ, nm
0
1
2
3
4
Irradiation time, hours
Fig. 2. (a) Evolution of the UV absorption spectrum of FLUA in aqueous solution
upon irradiation within the range 300–450 nm. (b) Evolution of the concentration
as a function of irradiation time. ([FLUA] = 5.0 ꢀ10ꢁ5 mol Lꢁ1, pH 4.8).
Fig. 4. Effect of the oxygen concentration on the photodegradation of FLUA upon
irradiation at the range 300–450 nm.
3.2. The effect of pH
These spectroscopic data indicate that FLUA is able to absorb
solar light and thus to undergo direct phototransformation, which
is very interesting from the environmental point of view. Indeed,
the direct photolysis of FLUA under artificial light within the range
300–450 nm in aerated aqueous solutions was investigated. Dark
control samples were analyzed in order to ensure a negligible
effect of thermal reactions in the same conditions.
The kinetics of FLUA photolysis in aqueous solution has been
studied at different pH values, 3.0, 4.8 and 7.0. As clearly shown in
Fig. 3a, the pH of the FLUA solution has an obvious influence on the
direct photolysis rate. The degradation rate increased when the pH
increased. It is evident that different pH values of the solution
make difference in the absorption spectrum of the solution. Thus,
an increase of the absorbance is clearly observed within the
wavelength rage 300–350 nm when the pH decreases (Fig. 3b). This
significant change is attributed to the ionization process of FLUA in
aqueous solution owing to the protolytic equilibrium with a pKa of
4.17 [26]. In order to take into account for this change in
absorption, we calculated the disappearance quantum yield. This
was evaluated to 1.2 ꢀ10ꢁ5, 1.1 ꢀ10ꢁ4 and 1.2 ꢀ10ꢁ4, at pH 3.0,
4.8 and 7.0 respectively. No difference in the disappearance
quantum yield was observed within the pH range 5.0–11.0 indicat-
ing that the higher photoreactivity of the anionic form.
As clearly shown in Fig. 2, upon irradiation of FLUA at a
concentration of 2.0 ꢀ10ꢁ5 mol Lꢁ1 and pH 4.8, we observe a
decrease of the absorbance at
l< 320 nm and a significant increase
for higher wavelengths without a significant change of the pH.
These are owing to the disappearance of FLUA and the formation of
byproducts respectively indicating that flufenamic acid is effi-
ciently photodegraded by direct irradiation. The HPLC analysis of
the irradiated solution showed that about 50% conversion was
obtained in 1hour and a complete transformation was achieved by
an irradiation period of roughly 6 h.
The quantum yield of FLUA phototransformation was measured
in air-saturated solutions and pH of 4.8, by using monochromatic
lights at 290 and 310 nm. It was evaluated (in both irradiation
conditions) to about 1.1 ꢀ10ꢁ4 indicating that the photochemical
behavior in not excitation wavelength dependent. Moreover, no
effect of the light intensity was observed under our experimental
conditions.
3.3. Effect of oxygen concentration
It is well known that in aqueous medium, molecular oxygen
may have dual roles in the photochemical behavior of organic
pollutants. For example, It could quench the molecules excited
triplet states resulting in the decrease of the conversion rate by the
0,4
(a)
(b)
1,0
0,3
0,2
0,1
0,0
pH=10.6
pH=7.3
pH=4.8
pH=3.1
pH=1.9
0,8
pH = 3
pH = 4,8
pH = 7
0,6
0,4
0,2
0,0
200
250
300
λ, nm
350
400
0
1
2
3
4
Irradiation time, hours
Fig. 3. (a) Effect of pH on the photodegradation rate of FLUA in aqueous solution irradiated within the range 300–450 nm. (b) Effect of pH on the absorption spectrum of FLUA.

4
S. Rafqah, M. Sarakha / Journal of Photochemistry and Photobiology A: Chemistry 316 (2016) 1–6
These results were confirmed by evaluating the quantum yield
in different conditions and by monochromatic excitation at
310 nm. This was found constant and equal to 1.1 ꢀ10ꢁ4
.
3.4. Identification of photolysis products of FLUA
The irradiated solution of FLUA, at natural pH, was analyzed by
using chromatographic technique such as HPLC (Fig. 5). Under
tirr= 30 min
these conditions,
a single photoproduct resulting from the
irradiation of FLUA was clearly seen at a retention time of 4.0 min.
HPLC coupled to mass spectrometry (LC–ESI–MS) screening
method using a MS/MS spectral library for the identification of
xenobiotic substances has been developed and validated. This
method is a selective and accurate method that allowed the
determination of selected non-steroidal anti-inflammatory drugs
(NSAIDs), either individually or in mixtures [29].
tirr = 0
0
2
4
6
8
10
12
14
Retention time, minutes
Fig. 5. HPLC chromatogram of the initial and irradiated solutions of FLUA at the
initial concentration of 50
mol Lꢁ1. The conversion percentage was roughly 28%.
m
First, flufenamic acid was analyzed in ESI(+) mode, giving a
mass value at m/z = 282 together with a daughter fragment ion at
m/z = 264. The latter corresponds to the loss of a water molecule.
This was then followed by the elimination of hydrogen fluoride
(HF) leading to a fragment ion at m/z = 244. The latter ion
undergoes the elimination of carbonyl group and then a second
elimination of hydrogen fluoride giving rise to two principal
fragments at m/z 216 and 196 respectively (Fig. 6a). The
determination of the chemical structure of the degradation
product was conducted using the same conditions. The obtained
MS–MS spectra are compiled in Fig. 6b.
1
generation of singlet oxygen, O2, or react with radical inter-
mediates leading to oxidation processes [26–28].
To examine the effect of oxygen on the photodegradation rates
of FLUA, photochemical irradiations were carried out in aqueous
solutions at different oxygen concentrations with a stream of
nitrogen gas ([O2] < 1.0 ꢀ10ꢁ5 mol Lꢁ1) or of oxygen gas ([O2] = 1.29
ꢀ 10ꢁ3 mol Lꢁ1) an aerated solutions ([O2] = 2.6 ꢀ10ꢁ4 mol Lꢁ1). As
far as the initial degradation rate is concerned, Fig. 4 clearly shows
that similar initial degradation rates were obtained for the three
used oxygen concentration. This indicates, within the experimen-
tal errors, that oxygen is not significantly involved in the
photochemical degradation process of FLUA.
FLUA parent ion and byproduct ion differed by 24 units of mass.
These results clearly show that the direct photodegradation of
FLUA involves an interesting reaction where the CF3 group is
converted to COOH more likely by hydrolysis reaction.
Fig. 6. LC/ESI/MS/MS chromatogram in positive mode for (A) FLUA and its byproduct (B).
F
C
F
C
CO2H
CO2H
F
CO2H
F
CO2H
NH
O
CF3
NH
H
NH
OH
- HF
H2O/h
F
H
- HF
AFLU
F
C
F
C
OH
OH
CO2H
O
CO2H
NH
NH
NH
C
- H2O
H2O/h
- HF
O
OH
2,3'-imino-dibenzoic acid
Scheme 1. Proposed mechanism for the phototransformation of flufenamic acid in aqueous solution.

S. Rafqah, M. Sarakha / Journal of Photochemistry and Photobiology A: Chemistry 316 (2016) 1–6
5
2,0
1,5
1,0
0,5
0,0
(b)
Byproduct
40
30
20
10
0
1,6
(a)
1,5
0,100
1,2
Flufenamic acid
FLUA
F-
0,075
0,050
0,025
0,000
Photoproduct
1,0
0,5
0,0
0,8
0,4
0,0
250
300
, nm
350
400
λ
FLUA
2
0
2
4
6
8
10
0
4
6
Irradation time, hours
Irradiation time, minutes
Fig. 7. Kinetic of FLUA phototransformation and formation of byproduct (2,30-imino-dibenzoic acid (a) and fluoride ions (b) a function of irradiation time.
In fact the mass spectra of the photoproduct (m/z 258) and its
generated daughter fragments corresponding to the loss of two
consecutive water molecules (m/z 240 and 222) and two
consecutive carbon monoxide molecules (m/z 194 and 166), were
clearly observed. They perfectly confirm the proposed structure of
the generated byproduct as 2,30-imino-dibenzoic acid.
The proposed mechanism for the photodegradation of flufe-
namic acid is shown in (Scheme 1). The degradation pathway
under UV-irradiation is the photohydrolysis of a CꢁꢁF bond. This
reaction has been previously observed for several compounds
containing a trifluoromethyl group (Table 1).
very important to note that the mefemanic acid, which presents a
methylene group (CH3) instead of CF3 as in the flufenamic acid, did
not undergo any degradation upon light irradiation under the same
conditions.
Fig. 7a shows a typical time course of FLUA photodegradation in
aqueous solution as discussed previously. Since the generated
product is commercial a quantitative analysis was undertaken by
performing a calibration curve. Under our experimental condi-
tions, similar values of the degradation rate of FLUA and the
formation rate of the byproduct 2,30-imino-dibenzoic acid were
obtained indicating the selective photoreactivity of flufenamic
acid.
These results show that this photodegradation product is
obtained with nearly stoichiometric proportion to the parent since
they have the same evolution kinetic curves. It is worth noting that
flufenamic acid and its generated product present roughly the
same absorption spectrum (Fig. 7a).
The formation of the photoproduct 2,30-imino-dibenzoic acid
may follow the same mechanistic pathway. This photohydrolysis is
owing to the electron-withdrawing effect of the carboxylic
function, which inhibits the release of a halogen ion when it is
not assisted by the heterolytic scission of a molecule of water. It is
As shown in Fig. 7b, the phototransformation of FLUA generates
fluoride species that were easily detected and analyzed by ionic
chromatography. Such Fig. compares the released Fluoride ions
concentration and the disappearance amount of FLUA. As clearly
observed, under our experimental conditions, the initial rates for
FLUA degradation and Fluoride ions are perfectly similar indicating
the involvement of a unique photochemical. This was evaluated to
about 1.2 ꢀ10ꢁ7 mol Lꢁ1 minꢁ1. Moreover, when flufenamic acid at
the initial concentration of 1.6 ꢀ10ꢁ6 mol Lꢁ1, is photochemically
and entirely converted to 2,30-imino-dibenzoic acid, the obtained
Table 1
Photohydrolysis of the CꢁꢁF bond of the compounds containing a trifluoromethyl
group presented in litterature.
Products
Photoproducts
Ref
[30,31]
concentration of fluoride ions was evaluated, as 4.2 ꢀ10ꢁ5 mol Lꢁ1
.
[32]
[33]
[34]
This result is compatible with that calculated while multiplying by
a factor of three 3 the initial concentration of FLUA (analyzed by
HPLC) in good agreement with the molecular structure (Fig. 7b).
4. Conclusion
The total transformation of the flufenamic acid under direct
photochemical irradiation in solution was obtained in 6 h under
our experimental conditions. The photochemical transformation
was studied according to several parameters such as the effect of
oxygen, pH and excitation wavelength. A single photoproduct was
obtained namely 2,30-imino-dibenzoic acid. Its structure as well as
its selective formation was confirmed by LC-mass technique and by
HPLC calibration using the standard compound. This is in
agreement of the defluoration of the flufemanic acid in aqueous
solution. Based on these results, a photochemical degradation
mechanism of flufenamic acid was proposed.

6
S. Rafqah, M. Sarakha / Journal of Photochemistry and Photobiology A: Chemistry 316 (2016) 1–6
[15] D.W. Kolpin, E.T. Furlong, M.T. Meyer, E.M. Thurman, S.D. Zaugg, L.B. Barber, H.
Acknowledgement
T. Buxton, Environ. Sci. Technol. 36 (2002) 1202.
[16] K. Hoshina, S. Horiyama, H. Matsunaga, J. Haginaka, J. Pharm. Biomed. Anal. 55
(2011) 916.
This work was supported by the Agence Universitaire de la
Francophonie (AUF) as part of the award for the development of
mobility training and research in 2011 “Bourse de mobilité pour le
perfectionnement à la formation et à la recherche”.
[17] C. Tixier, H.P. Singer, S. Oellers, S.R. Mueller, Environ. Sci. Technol. 37 (2003)
1061.
[18] J.L. Packer, J.J. Werner, D.E. Latch, K. McNeill, W.A. Arnold, Aquat. Sci. 65 (2003)
342.
[19] Y. Zhang, S.U. Geißen, C. Gal, Chemosphere 73 (2008) 1151.
[20] P. Bartels, W.v Tümpling Jr., Sci. Total Environ. 374 (2007) 143.
[21] H. Yau, G. Baranauskas, M. Martina, J. Physiol. 588 (2010) 3869.
[22] Y. Chi, K. Li, Q. Yan, S. Koizumi, L. Shi, S. Takahashi, Y. Zhu, H. Matsue, M. Takeda,
M. Kitamura, J. Yao, J. Pharmacol. Exp. Ther. 339 (2011) 257.
[23] A.A. Fatma, A.A. Salma, A.A. Abdulrahman, Anal. Chim. Acta 416 (2000) 87.
[24] T. Perez-Ruiz, C. Martinez-Lozano, A. Sanz, E. Bravo, J. Chromatogr. B 708
(1998) 249.
[25] J.G. Calvert, J.M. Pitts, Photochemistry, Wiley, New York, 1996, pp. 783.
[26] A. Muñoz de la Peña, N. Mora Díez, D. Bohoyo Gol, A.C. Olivieri, G.M. Escander,
Anal. Chim. Acta 569 (2006) 250.
[27] X.D. Zhu, Y.J. Wang, C. Liu, W.X. Qin, D. Zhou, Chemosphere 10 (2014) 274.
[28] P. Wong-Wah-Chung, S. Rafqah, G. Voyard, M. Sarakha, J. Photochem.
Photobiol. A. Chem. 191 (2007) 201.
References
[1] W. Xu, G. Zhang, X. Li, S. Zoun, P. Li, Z. Hu, J. Li, Water Res. 41 (2007) 4526.
[2] R. Rosal, A. Rodríguez, J.A. Perdigón-Melón, A. Petre, E. García-Calvo, M.J.
Gómez, A. Agüera, A.R. Fernández-Alba, Water Res. 44 (2010) 578.
[3] E. Zuccato, S. Castiglioni, R. Bagnati, M. Melis, R. Fanelli, J. Hazard. Mater. 179
(2010) 1042.
[4] M. Gros, M. Petrovic’, A. Ginebreda, D. Barceló, Environ. Int. 36b (2010) 15.
[5] J. Fick, H. Söderström, R.H. Lindberg, C. Phan, M. Tysklind, D.G.J. Larsson,
Environ. Toxicol. Chem. 28 (2009) 2522.
[6] C.G. Daughton, T.A. Ternes, Environ. Health Perspect. 107 (1999) 907.
[7] T.A. Ternes, M. Meisenheimer, D. McDowell, F. Sacher, H.J. Brauch, B. Haist-
Gulde, G. Preuss, U. Wilme, N. Zulei-Seibert, Environ. Sci. Technol. 36 (2002)
3855.
[8] C. Sirtori, A. Zapata, W. Gernjak, S. Malato, A. Agüera, Chemosphere 88 (2012)
627.
[9] S.K. Khetan, T.J. Collins, Chem. Rev. 107 (2007) 2319.
[10] Y. Li, J. Niu, W. Wang, Chemosphere 85 (2011) 892.
[11] A.Y.C. Lin, Y.C. Lin, W.N. Lee, Environ. Pollut. 187 (2014) 170.
[12] D. Fatta-Kassinos, M.I. Vasquez, K. Kümmerer, Chemosphere 85 (2011) 693.
[13] A.A. Gouda, M.I.K. El-Sayed, A.S. Amin, R. El Sheikh, Arabian J. Chem. 6 (2013)
145.
[29] M.E. Abdel-Hamid, L. Novotny, H. Hamza, J. Pharm. Biomed. Anal. 24 (4) (2001)
587.
[30] M. Petrovic, D. Barcelo, Trends Anal. Chem. 6 (2007) 26.
[31] W.L. Monica, C.J. Young, S.A. Maburty, Environ. Sci. Technol. 39 (2005) 513.
[32] D.A. Ellis, S.A. Maburty, Environ. Sci. Technol. 34 (2000) 632.
[33] F. Bosca, M.C. Cuquerella, M.L. Marı’n, M.A. Miranda, Photochem. Photobiol. 73
(5) (2001) 463.
[34] S. Halladja, A. Amine-Khodja, A. Ter Halle, A. Boulkamh, C. Richard,
Chemosphere 69 (2007) 1647.
[14] B. Halling-Sørensen, S.N. Nielsen, P.F. Lanzky, F. Ingerslev, H.C. Holten Lu
̈tzhøft,
S.E. Jørgensen, Chemosphere 36 (1998) 357.