Kinetic and chemical assessment of the UV/H2O2 treatment of antiepileptic drug carbamazepine

Article abstract of DOI:10.1016/S0045-6535(03)00757-4

The UV/H₂O₂-induced degradation of carbamazepine, a worldwide used antiepileptic drug, recently found as contaminant in many municipal sewage treatment plant (STP) effluents and other aquatic environments, is investigated. The oxidation treatment caused an effective removal of the drug. At complete abatement of the substrate after 4 min treatment, a 35% value of removed total organic carbon (TOC) was obtained. A kinetic constant of (2.05 ± 0.14) × 10⁹ 1 mol^-1 s^-1 was determined for OH radical attack to carbamazepine in the UV/H₂O ₂ process. Preparative TLC of the reaction mixture led to the isolation of acridine-9-carboxaldehyde as a reaction intermediate. HPLC and GC/MS analysis indicated formation of small amounts of acridine, salicylic acid, catechol and anthranilic acid among the reaction products. Under the same reaction conditions, synthetically prepared 10,11-epoxycarbamazepine was easily degraded to acridine as main product, suggesting that this epoxide is a likely intermediate in the oxidative conversion of carbamazepine to acridine. Under sunlight irradiation, carbamazepine in water underwent slow degradation to afford likewise acridine as main product. In view of the mutagenic properties of acridine, these results would raise important issues concerning the possible environmental impact of carbamazepine release through domestic wastewaters and support the importance of prolonged oxidation treatments to ensure complete degradation of aromatic intermediates.

Full text of DOI:10.1016/S0045-6535(03)00757-4

Chemosphere 54 (2004) 497–505
www.elsevier.com/locate/chemosphere
Kinetic and chemical assessment of the UV/H2O2 treatment
of antiepileptic drug carbamazepine
a
Davide Vogna , Raffaele Marotta , Roberto Andreozzi ,
b
b
a,
a
Alessandra Napolitano *, Marco d’Ischia
a
Department of Organic Chemistry and Biochemistry, University of Naples ‘‘Federico II’’, Complesso Universitario M.S. Angelo,
via Cinthia 4, I-80126 Naples, Italy
b
Department of Chemical Engineering, University of Naples ‘‘Federico II’’, Piazzale Tecchio, I-80125 Naples, Italy
Received 11 February 2003; received in revised form 18 July 2003; accepted 29 July 2003
Abstract
The UV/H2O2-induced degradation of carbamazepine, a worldwide used antiepileptic drug, recently found as
contaminant in many municipal sewage treatment plant (STP) effluents and other aquatic environments, is investigated.
The oxidation treatment caused an effective removal of the drug. At complete abatement of the substrate after 4 min
treatment, a 35% value of removed total organic carbon (TOC) was obtained. A kinetic constant of (2.05 0.14) · 109
l molꢀ1 sꢀ1 was determined for OH radical attack to carbamazepine in the UV/H2O2 process. Preparative TLC of the
reaction mixture led to the isolation of acridine-9-carboxaldehyde as a reaction intermediate. HPLC and GC/MS
analysis indicated formation of small amounts of acridine, salicylic acid, catechol and anthranilic acid among the re-
action products. Under the same reaction conditions, synthetically prepared 10,11-epoxycarbamazepine was easily
degraded to acridine as main product, suggesting that this epoxide is a likely intermediate in the oxidative conversion of
carbamazepine to acridine. Under sunlight irradiation, carbamazepine in water underwent slow degradation to afford
likewise acridine as main product. In view of the mutagenic properties of acridine, these results would raise important
issues concerning the possible environmental impact of carbamazepine release through domestic wastewaters and
support the importance of prolonged oxidation treatments to ensure complete degradation of aromatic intermediates.
ꢀ 2003 Elsevier Ltd. All rights reserved.
Keywords: Acridine; AOP; Carbamazepine; Mineralization; Oxidation; UV/H2O2
1. Introduction
alized countries during the past decades many medicinal
classes, including betablockers, sympathomimetics, an-
tiphlogistics, lipid regulators, antibiotics, vasodilators
and so on, have been detected at concentration levels up
to micrograms per liter in various aquatic environments.
A typical case in point is that of carbamazepine, a
worldwide used antiepileptic drug currently prescribed
for treatment of a range of other medical conditions,
such as chronic pain, and for psychopharmacotherapy,
which is consumed in England in quantities of more than
40 t/yr (Jones et al., 2002). Carbamazepine has been
identified along with other pharmaceuticals in German
feeding waters for waterworks (rivers, bank filtrates and
Pharmaceutical substances and personal care prod-
ucts have recently been recognized as an important class
of organic pollutants increasingly found in wastewaters
from urban areas, including effluents from sewage
treatment plants (STP) (Daughton and Ternes, 1999;
Zuccato et al., 2000; Heberer, 2002). In most industri-
* Corresponding author. Tel.: +39-08-167-4133; fax: +39-08-
167-4393.
E-mail address: alesnapo@unina.it (A. Napolitano).
0045-6535/$ - see front matter ꢀ 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S0045-6535(03)00757-4

498
D. Vogna et al. / Chemosphere 54 (2004) 497–505
groundwater) (Ternes, 1998), in river and lake waters at
concentrations varying from 35 ng lꢀ1 up to 800 ng lꢀ1
(Ollers et al., 2001), as well as in many municipal sew-
age treatment plant effluents in Germany, Switzerland
(Daughton and Ternes, 1999; Ollers et al., 2001), Italy,
France, Greece and Sweden (Andreozzi et al., 2003) and
was also found with a concentration of 30 ng lꢀ1 in
drinking water (Ternes, 2001).
mercury monochromatic lamp emitting at 254 nm (He-
lios Italquartz) in a 0.420 l photoreactor. The concen-
tration of hydrogen peroxide solution was determined
by iodometric titration (Treadwell and Hall, 1935).
The power output of the lamp was 2.7 · 10ꢀ6 E sꢀ1 as
measured by hydrogen peroxide actinometry (Nicole
et al., 1990). The pH of reaction mixtures was adjusted
to the desired values with perchloric acid and/or sodium
hydroxide. When required humic acids at different
concentrations were included in the carbamazepine so-
lutions.
Although up to now no specific adverse effects on
human health can be ascribed to carbamazepine and
other pharmaceuticals as water contaminants and their
environmental impact is still to be defined, the precau-
tionary principle warrants current efforts aimed at de-
veloping efficient treatment methodologies for removing
pharmaceutical contaminants from aquatic environ-
ments.
2.3. Sunlight irradiation
Solar photodegradation experiments were carried out
during Spring at Naples in the South of Italy (40ꢁN–
14ꢁE) in 0.5 dm3 annular magnetically stirred glass re-
actors thermostated at 25 ꢁC. Aqueous solutions of
carbamazepine for irradiation included humic acids or
nitrate salts at appropriate concentrations.
Sand filtration and flocculation by iron(III) chloride
proved to be unsuitable for the efficient removal of
carbamazepine and other selected contaminants (Ternes
et al., 2002). Ozonation, on the other hand, was found to
be very effective for the degradation and partial miner-
alization of carbamazepine (Andreozzi et al., 2002), but
the potential offered by advanced oxidation processes
(AOPs) has not yet been fully assessed, and no detailed
analysis of intermediate and degradation products of
carbamazepine during AOP is available. This is yet an
important gap since abatement of contaminants pro-
vides only a partial indication of the efficiency of the
treatment, and the generation of toxic intermediates
more resilient to degradation should not be overlooked
when comparing different methodologies.
2.4. Analytical methods
GC–MS analyses were carried out on a Saturn 2000
apparatus (Varian) equipped with an Ion Trap detector.
A DB5-MS fused silica column (Zorbax, 30 m · 0.25 mm
ID, 0.25 lm film thickness) was used. Helium was the
carrier gas with a 1 ml minꢀ1 flow rate. The temperature
program was as follows: 100 ꢁC for 2 min, 10 ꢁC minꢀ1
up to 250 ꢁC, hold time 10 min. The injector and GC/
MS transferline were taken 250 and 170 ꢁC, respectively.
The MS detector was operated in the EI mode, scanning
in the range 40–640 amu.
In the present paper the authors report a detailed
investigation of the advanced oxidation process of
carbamazepine with the UV/H2O2 system. The kinetics
of the process were investigated and the nature of the
primary intermediates and by-products assessed by dif-
ferent analytical techniques.
HPLC analyses were performed on a Hewlett Pack-
ard 1100 liquid chromatograph using a UV diode array
detector. For carbamazepine and acridine analysis a
Sinergy RP-max (4.6 · 25 mm) column was used. Elu-
tion conditions were as follows: 0.07 M phosphate buffer
pH ¼ 2.0 containing 5% CH3OH (solvent A), CH3CN
(solvent B) 0–5 min: 5% solvent B; 5–25 min: from 5% to
25% solvent B gradient; 25–35 min: 25% solvent B. The
flow rate was 1.0 ml minꢀ1, and the detection wavelength
was set at 254 and 300 nm.
2. Materials and methods
2.1. Chemicals
Hydrogen peroxide (30% w/w) and humic acid
(technical grade) were purchased from Fluka. Carb-
amazepine, 3-chloroperbenzoic acid, acridine, acridone,
iminostilbene, salicylic acid, catechol and anthranilic
acid were from Sigma-Aldrich. All other chemicals were
of the highest grade commercially available and were
used as obtained. Doubly glass-distilled water was used
throughout this study.
Total organic carbon (TOC) was monitored by a
TOC analyzer (Shimadzu 5000 A). 1H and 13C-NMR
spectra were recorded at 400.1 and 100.6 MHz, respec-
tively, on a 400 MHz Bruker spectrometer or at 200.2
and 50.1 MHz, respectively on a 200 MHz Gemini
Varian spectrometer.
2.5. Product analysis
2.2. UV/H2O2 oxidation
Aliquots (5 ml) of the oxidation mixture of carb-
amazepine were periodically withdrawn and directly
injected on HPLC. For GC–MS analysis withdrawals
were lyophilised and the residue dissolved in methanol
Carbamazepine or benzoic acid solutions in water
were irradiated with a nominal 17 W low-pressure

D. Vogna et al. / Chemosphere 54 (2004) 497–505
and directly injected into GC–MS instrument. When
499
0.020
100
80
60
40
20
0
required the residue was treated with 1,1,1,3,3,3-hexa-
methyldisilazane (200 ll), anhydrous pyridine (200 ll)
and chlorotrimethylsilane (50 ll) (Li et al., 1999). The
resulting mixture was shaken vigorously for 1 min and
centrifugated to separate the precipitate formed prior to
injection into the chromatograph.
mM
0.015
0.010
0.005
0.000
National Institute of Standards and Technology
(NIST) Library searching was used for compound
identification. Identification of the most abundant com-
ponents was secured by comparison of the chromato-
graphic behaviour and fragmentation patterns with
those of authentic samples.
2.6. Product isolation
0
1
2
3
4
min
A solution of carbamazepine (118 mg, 0.5 mmol) and
hydrogen peroxide (100 mM) in water (500 ml) was ir-
radiated by UV light for 1 h. The mixture was extracted
with ethyl acetate (3 · 300 ml) and the combined organic
layers were dried over anhydrous sodium sulphate, and
taken to dryness under vacuum at 25 ꢁC. The residue (40
mg) was analyzed by preparative TLC on silica gel using
toluene/chloroform/methanol 8:5:1 as the eluant to af-
ford pure 9-acridincarboxaldehyde (Rf ¼ 0:82, 2 mg)
identified by comparison of the spectral properties with
those of a synthetic sample prepared according to Furst
and Uetrecht (1993).
Fig. 1. Carbamazepine decay by UV/H2O2 and TOC removed.
Carbamazepine was at 2.0 · 10ꢀ2 mM, H2O2 5.0 mM, pH of the
solution was adjusted to 5.0. Left axis: carbamazepine con-
sumption by UV in the presence (N) or in the absence (j) of
H2O2; right axis: TOC removed in the UV/H2O2 reaction (r).
lytic process. OH radical exhibits a high oxidation po-
tential (Eo ¼ 2:8 V) (Juang et al., 1998) and can bring
attack to a broad range of organic compounds causing
eventually their mineralization through sequential hy-
droxylation–dehydrogenation–breakdownsteps(Gulyas,
1997; Andreozzi et al., 1999).
2.7. Synthesis of 10,11-epoxycarbamazepine
Fig. 1 reports the consumption of carbamazepine in
aqueous solution (2.0 · 10ꢀ2 mM) by UV/H2O2 treat-
ment and the TOC removed. The rate of carbamazepine
decay was relatively high, with an associated removed
total organic carbon (TOC) of about 35% when sub-
strate degradation was complete (ꢁ4 min). Over the
same reaction time, direct photolysis of carbamazepine
was negligible in the absence of H2O2 (full squares in the
figure).
To a solution of carbamazepine (100 mg, 0.42 mmol)
in anhydrous ethyl ether (10 ml) 3-chloroperbenzoic acid
(73 mg, 0.42 mmol) was added under stirring. After 24 h
the mixture was taken to dryness. The residue was pu-
rified by column chromatography on alumina using
chloroform/methanol 98:2 as the eluant to afford 10,11-
epoxycarbamazepine (70 mg, 66%) homogeneous to
TLC analysis on silica gel (chloroform/methanol 95:5, Rf
0.51). 1H NMR (CDCl3) d (ppm): 4.28 (s), 4.51 (bs), 7.34
(m), 7.42 (m), 7.50 (d, J ¼ 8:0 Hz); 13C NMR (CDCl3) d
(ppm): 51.3 (CH), 121.0 (CH), 122.8 (CH), 123.1 (CH),
124.1 (CH), 124.3 (C), 130.9 (C), 150.7 (C).
Carbamazepine degradation by UV/H2O2 treatment
was not affected by changing the pH of the solution in
the range of 2.0–8.0 (data not shown). The influence of
humic acids (4–30 mg lꢀ1), typical constituents of natural
aquatic environments, on carbamazepine abatement was
also investigated (Fig. 2).
10,11-Epoxycarbamazepine was converted to acri-
dine-9-carboxaldehyde, Rt ¼ 10:52 min, m=z 207 (Mþ,
100) under the conditions of GC–MS analysis as de-
scribed (Frigerio et al., 1973).
The results indicated a decrease of the system reac-
tivity for humic acid concentrations higher than 4.0
mg lꢀ1, mainly due to the capability of these species to
consume hydroxyl radicals (Gao and Zepp, 1998). In fact
a simplified analysis based on an approximate rate con-
stant of HO radical attack on humic acid, 2.0 · 104
3. Results and discussion
mgꢀ1 l sꢀ1 (Hoigne, 1998), allows to calculate ascaveng-
ꢀ
3.1. Carbamazepine degradation with UV/H2O2
ing term in the range of 8 · 104–6 · 105 sꢀ1 at concen-
trations varying from 4.0 to 30 mg lꢀ1. These results
indicate that for humic acid concentrations equal to
12 or 30 mg lꢀ1 a scavenging effect higher than that due to
UV radiation at 254 nm causes the photolysis of
H2O2 into OH radicals as a result of the primary photo-

500
D. Vogna et al. / Chemosphere 54 (2004) 497–505
2/
d½Sꢂ
H2O2
¼ ꢀkp ꢃ
dt
Vsol
Io ꢃ ½1 ꢀ expðꢀ2:3lðeH O ꢃ ½H2O2ꢂ þ eS ꢃ ½SꢂÞÞꢂ ꢃ ½Sꢂ
2
2
ꢃ
kh ꢃ ½H2O2ꢂ þ kp ꢃ ½Sꢂ
ꢃ fH O
ð1Þ
2
2
/
d½H2O2ꢂ
dt
H2O2
¼ ꢀ
ꢃ Io ꢃ ½1 ꢀ expðꢀ2:3lðeH ꢃ ½H2O2ꢂ þ eS ꢃ ½SꢂÞÞꢂ
2O2
Vsol
/
H2O2
ꢃ fH ꢀ kh ꢃ
2O2
Vsol
Io ꢃ ½1 ꢀ expðꢀ2:3lðeH ꢃ ½H2O2ꢂ þ eS ꢃ ½SꢂÞÞꢂ ꢃ ½H2O2ꢂ
2O2
ꢃ
kh ꢃ ½H2O2ꢂ þ kp ꢃ ½Sꢂ
ꢃ fH
ð2Þ
2O2
Fig. 2. Effect of humic acids on carbamazepine decay. Carb-
amazepine was at 8.0 · 10ꢀ3 mM, H2O2 at 5.0 mM in solutions
at pH 5.5. Experiments were run in the presence of humic acids,
where /H O is the primary quantum yields of the direct
2
2
photolysis at 254 nm of hydrogen peroxide (/H O ¼ 0:5
2
2
mol Eꢀ1) (Baxendale and Wilson, 1957), Vsol is the vol-
ume of the aqueous solution (0.42 l), Io is the measured
lamp UV-light intensity at 254 nm (2.7 · 10ꢀ6 E sꢀ1), l is
the optical pathlength (0.201 dm) of the reactor, eS and
eH O are the molar extinction coefficients at 254 nm for
4 mg lꢀ1 (N), 12 mg lꢀ1 (r), 30 mg lꢀ1
( ); or without H O and
2 2
ꢄ
with humic acids at 4 mg lꢀ1 (+); or without humic acids and in
the presence of H2O2 ( ).
ꢅ
2
2
hydrogen peroxide at a concentration of 5.0 mM
(kh Æ[H2O2]¼2.7 · 107 lmolꢀ1 sꢀ1 Æ5.0·10ꢀ3 mollꢀ1 ¼ 1.35 ·
105 sꢀ1) is expected.
carbamazepine (6025 molꢀ1 l cmꢀ1) and hydrogen per-
oxide (18.6 l dm3 cmꢀ1) respectively, fH O represents
2
2
the UV fraction absorbed by hydrogen peroxide and kh
(2.7 · 107 molꢀ1 l sꢀ1 (Buxton et al., 1988)) is the ki-
netic constant for HO radical attack to hydrogen per-
oxide.
3.2. Kinetic analysis
Reaction kinetics were assessed by following the ap-
proach successfully proposed by Alnaizy and Akergman
(2000) for phenol.
The best value of kp constant was estimated by
comparing the data collected at pH ¼ 5.0 during exper-
imental runs at different carbamazepine (1.0 · 10ꢀ3
,
A simplified kinetic scheme (r1–r4) was adopted to
describe the kinetics of the reaction behaviour of carb-
amazepine by UV radiation in the presence of hydrogen
peroxide. This assumes that the photolysis of hydrogen
peroxide at 254 nm generates highly reactive species
(hydroxyl radicals)which attack the substrate and hy-
drogen peroxide.
2.0 · 10ꢀ3, 4.0 · 10ꢀ3 and 8.0 · 10ꢀ3 mM) and hydrogen
peroxide (2.0, 5.0 and 7.5 mM) concentrations with
those calculated by means of Eqs. (1) and (2). These
were integrated with the following initial conditions:
[S] ¼ [S]0 and [H2O2] ¼ [H2O2]0. The best estimated value
for kp, (2.05 0.14) · 109 l molꢀ1 sꢀ1, was chosen as that
which minimizes the sum of the square of the differ-
ence between calculated and measured substrate con-
centrations at different reaction times during a single
run.
hm
H2O2!2HOꢀ
ðr1Þ
ðr2Þ
ðr3Þ
ðr4Þ
The value of kp found in this study is lower than that
(8.8 1.2) · 109 l molꢀ1 sꢀ1 recently reported by others
(Huber et al., 2003). To assess the reliability of the pre-
sent procedure, in a separate set of experiments the
H2O2/UV treatment was applied to benzoic acid as a
standard compound, for which a kinetic constant of
4.3 · 109 l molꢀ1 sꢀ1 for HO attack was expected at
pH 6 3.0 (Buxton et al., 1988). An oxidation run was
thus carried out at pH ¼ 3.0 by following benzoic
acid decay, starting from [H2O2] ¼ 2.0 · 10ꢀ2 mol lꢀ1 and
[benzoic acid] ¼ 5.0 · 10ꢀ5 mol lꢀ1 as previously de-
scribed. Application of the kinetic model allowed to es-
kp
HOꢀ þ S!Sꢀ
kh
HOꢀ þ H2O2!H2O þ HOꢀ
2
kt
2HOꢀ !H2O2 þ O2
2
Considering that UV direct photolysis of the substrate is
negligible during its complete removal and taking the
steady-state hypothesis for the HO and HO2 radicals,
the rates of consumption of carbamazepine and hydro-
gen peroxide can be expressed as follows:
timate a kinetic constant of 3.07 0.33 · 109 l molꢀ1 sꢀ1
which is comparable to the literature datum.
,

D. Vogna et al. / Chemosphere 54 (2004) 497–505
501
Moreover, it is clear that since
array detection, and TLC. Product analysis at 30 min
reaction time indicated the presence of several compo-
nents in small amounts, eluting between 16 and 21 min,
which exhibited chromophores typical of acridine de-
rivatives. The major of these products (eluted at 17.6
min) was identified as the parent acridine by comparison
of the chromatographic behaviour and UV spectrum
with those of an authentic sample.
(1) the relevant assumption for the development of the
model was that the reaction between HO radical
and oxidation by-products was negligible;
(2) and that this assumption strictly holds for a fixed
starting [H2O2] when the initial substrate concentra-
tion goes to zero.
Fig. 4 shows acridine formation by degradation of
0.5 mM carbamazepine with UV/H2O2. After 20 min
acridine reached the maximum concentration of 5 lM.
Although it is possible that such low yields denote for-
mation of acridine from a minor degradation path of
carbamazepine, the kinetic constant for OH radical at-
tack to acridine (5.8 · 109 l molꢀ1 sꢀ1 (Milano et al.,
1995)) would also be compatible with decomposition of
this intermediate as soon as it is produced.
The result obtained can be validated by performing an
oxidative run on carbamazepine with an initial concen-
tration equal to 4.2 · 10ꢀ8 M. In Fig. 3 the results col-
lected during this run are compared with the decay
predicted by using the above-reported model with
kp ¼ 2:05 ꢆ 109 l molꢀ1 sꢀ1, thus demonstrating the va-
lidity of the present kinetic model.
Preparative TLC of the ethyl acetate extractable
fraction of the mixture allowed isolation of a relatively
apolar reaction product which was identified as acridine-
9-carboxaldehyde (ꢁ2% isolated yield) by comparison of
the 1H NMR and mass spectrum with that of a syn-
thetic sample prepared by oxidation of iminostilbene
with m-chloroperbenzoic acid (Furst and Uetrecht,
1993).
3.3. Mechanism of carbamazepine oxidation by the H2O2/
UV system and intermediate/product analysis
In another series of experiments the intermediates
and products formed by H2O2/UV oxidation of carb-
amazepine were investigated to gain an insight into the
mechanism of the reaction. To this aim, carbamazepine
oxidation was carried out by treating aqueous solutions
of the drug at 0.5 mM concentration with 100 mM H2O2
under UV irradiation. At various intervals of time, the
mixture was analyzed by GC–MS, HPLC with diode
GC/MS runs showed well discernible peaks for both
acridone and iminostilbene, in addition to acridine and
acridine-9-carboxaldehyde. Injection of standard carb-
amazepine solution not exposed to the UV/H2O2 treat-
ment gave the same product pattern, though in lower
yield, suggesting that carbamazepine was thermally de-
composed to acridone and iminostilbene into the GC
apparatus. On the other hand, HPLC analysis did not
reveal detectable acridone nor iminostilbene.
0.005
mM
0.004
0.5
mM
0.4
0.3
0.2
0.1
0
0.003
0.002
0.001
0
0
10
20
30
40
50
min
Fig. 3. Comparison between experimental and predicted values
for H2O2/UV oxidation of carbamazepine at pH ¼ 5.5. Carb-
amazepine was at (d) 4.2 · 10ꢀ5 mM or (j) 4.3 · 10ꢀ3 mM,
H2O2 was at 5.0 mM. All points represent experimental data.
The rate of decay determined at concentrations of carbamaze-
pine of 4.3 · 10ꢀ3 mM was fitted with the experimental data
obtained at carbamazepine concentrations of 4.2 · 10ꢀ5 mM.
Fig. 4. Carbamazepine and acridine decay by UV/H2O2.
Carbamazepine was at 0.5 mM, H2O2 was at 100 mM, pH of
the solution was adjusted to 7.0. Left axis: carbamazepine
consumption (r). Right axis: profile of acridine concentration
during carbamazepine degradation, (j); decay of acridine alone
at 5.0 · 10ꢀ3 mM under the reaction conditions, (N).

502
D. Vogna et al. / Chemosphere 54 (2004) 497–505
To prevent or limit artifactual product formation by
An overall view of carbamazepine degradation path-
ways is provided in Fig. 5. This scheme is merely indi-
cative and is not intended to provide a comprehensive
representation of the actual complexities of the degra-
dation process. One of the initial steps may be hy-
droxylation of carbamazepine at the 10 position to give
a radical intermediate that can evolve to give 10,11-
epoxycarbamazepine. Subsequent opening of epoxide
ring would give a labile species that suffers facile ring
contraction to give 9-acridine-9-carboxaldehyde. This
latter would decompose to yield acridine (Furst and U-
etrecht, 1993). Support to this mechanism was obtained
in separate experiments in which synthetic 10,11-epoxy-
carbamazepine was exposed to the UV/H2O2 system to
give acridine among the reaction products. Alternatively,
oxidation of carbamazepine by OH radicals may occur
through initial attack to the aromatic ring moieties
leading to hydroxylated derivatives which may be prone
to breakdown via anthranilic acid, salicylic acid, catechol
and other intermediates. Anthranilic acid in particular
may conceivably arise by oxidative cleavage routes in-
volving the C10–C11 bond of carbamazepine.
degradation of carbamazepine into the GC injector
(Frigerio et al., 1973), GC–MS analyses were carried out
only when carbamazepine consumption was far com-
plete. Silylation treatment prior to injection into the gas
chromatograph was essential to permit analysis of
highly polar polyhydroxylated species and carboxylic
acids.
Table 1 shows main aromatic products identified by
GC–MS and their fragmentation peaks. Product iden-
tification was carried out by comparing chromato-
graphic and mass spectrometric behaviour with that of
authentic standards. The products with Rt 17.75 and
17.95 were assigned the structure of hydroxyacridine
isomers on the basis of the molecular peaks (m=z 267)
and the peak at 177 denoting loss of (CH3)3SiOH.
Anthranilic acid (2-aminobenzoic acid), salicylic acid
(2-hydroxybenzoic acid) and catechol (2-hydroxyphe-
nol) were also among the main detectable species, along
with hydroxyacetic, oxalic, malonic, oxaloacetic, ma-
leic, fumaric, succinic, tartronic, malic and tartaric
acids.
Table 1
Main aromatic species formed by carbamazepine identified by GC–MS analysis in comparison with authentic samples
Rt, min
Compound
IUPAC name,
CAS number
m=z(relative abundance %)
7.39a
2-Hydroxyphenol,
120-80-9
254(100), 239(45), 223(10),
147(9), 133(6), 73(15)
OH
OH
O
H
10.51
Acridine-9-carboxaldehyde,
885-23-4
207(100), 179(82), 151(18),
125(6), 100(4), 87(6), 75(12)
N
10.82a
11.33a
2-Hydroxybenzoic acid,
69-72-7
282(30), 267(100), 223(25),
193(35), 177(3), 165(7), 149(6),
126(12), 91(18), 73(70)
O
OH
OH
O
2-Aminobenzoic acid,
118-92-3
281(3), 266(19), 250(3), 232(6),
208(4), 192(6), 178(3), 149(6),
135(9), 118(6), 73(15)
OH
NH
2
13.74
Acridine,
260-94-6
179(100), 167(3), 152(6),
126(3), 113(2), 89(3), 75(5)
N
17.75 and 17.95a;b
1-Hydroxyacridine,
5464-73-3
and
267(100), 252(80), 224(9),
193(4), 177(10), 166(12),
139(5), 129(4), 117(5)
OH
N
2-Hydroxyacridine,
22817-17-0
a TMS derivative.
b Structural formulation based on fragmentation patterns.

D. Vogna et al. / Chemosphere 54 (2004) 497–505
503
.
O
OO
HO
O
.
.
HO / HO2
N
N
N
O
O
NH2
NH2
NH2
O
R
R
N
N
N
O
NH2
OH
R= COOH
N
COOH
NH2
COOH
OH
OH
OH
O
O
OH
O
HO
OH
OH
OH
OH
HO
HO
HO
O
O
O
O
OH
O
O
O
HO
OH
OH
OH
HO
HO
O
O
OH
O
O
O
Fig. 5. Carbamazepine degradation pathways induced by UV/H2O2 treatment.
3.4. Acridine formation by carbamazepine degradation in
aqueous solutions under solar irradiation
present as detectable product (HPLC) but not in the
dark experiments, reaching the maximum concentration
of 6 lM after 300 h exposure to sunlight in the presence
of humic acids and nitrate. Apparently, humic acids and
nitrate in the photolytic process act by enhancing carb-
amazepine decay, presumably by generation of reactive
Acridine belongs to azaarenes, an established class of
air and water pollutants with mutagenic and carcino-
genic activity (Shinohara et al., 1983; Furst and Uetr-
echt, 1993). The observed tendency of carbamazepine to
give acridine products during UV/H2O2 treatment and
the documented facility of iminostilbenes to undergo
ring contraction (Haque and Proctor, 1968; Haque
et al., 1972; Cann and Lezinisky, 1988) prompted us to
extend the study to carbamazepine degradation under
sunlight exposure in aqueous solution in presence of
humic acid and nitrate which are commonly present in
natural waters (Fig. 6). The aim of the experiments was
to determine whether acridine formation is a general
conversion route of carbamazepine under environmen-
tally relevant conditions.
ꢀ
oxygen species (Hoigne, 1998), without however induc-
ing accumulation of acridine. Thus, it appears that ac-
ridine formation is essentially induced by direct
photolysis.
4. Conclusions
The results of the present study indicate that UV/
H2O2 treatment can cause efficient abatement of carb-
amazepine partly via a series of acridine intermediates.
This is a typical case in which intermediate species are
more toxic and hazardous than the parent pollutant, and
failure to ensure complete mineralization of these species
during AOP may even worsen the environmental and
The results showed that carbamazepine was degraded
in all mixtures exposed to sunlight, and less then 10% in
the dark control experiments. In all cases, acridine was

504
D. Vogna et al. / Chemosphere 54 (2004) 497–505
logie Chimico–Fisiche of Naples University’’ for NMR
30%
25%
20%
15%
10%
5%
facilities and Dr. Italo Giudicianni and Miss Silvana
Corsani for technical assistance.
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