Materials Science and Engineering C 49 (2015) 493–499

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Materials Science and Engineering C

journalhomepage:www.elsevier.com/locate/msec

A zeolite modified carbon paste electrode as useful sensor for

voltammetric determination of acetaminophen
Leila Ahmadpour-Mobarakeh, Alireza Nezamzadeh-Ejhieh
Department of Chemistry, Shahreza Branch, Islamic Azad University, P.O. Box 311-86145, Shahreza, Isfahan, Iran
article info abstract

Article history: The voltammetric behavior of a carbon paste electrode modified with Co(II)-exchanged zeolite A (Co(II)-A/ZMCPE) for
Received 1 October 2014 determination of acetaminophen was studied. The proposed electrode showed a diffusion controlled reaction with the electron
Received in revised form 2 December 2014 −1
transfer rate constant (Ks) of 0.44 s and charge transfer coefficient of 0.73 in the absence of acet-aminophen. A linear
Accepted 6 January 2015 −1 2
voltammetric response was obtained in the range of 0.1 to 190 μmol L of acetaminophen [r = 0.9979, r = 0.9989 (n = 10)]
Available online 8 January 2015 −1
with a detection limit of 0.04 μmol L . The method was successfully applied to the analysis of acetaminophen in some drugs.
Keywords: © 2015 Elsevier B.V. All rights reserved.
Acetaminophen
Zeolite modified electrode
Carbon paste
Co(II)-A zeolite
Voltammetry

1. Introduction
Acetaminophen, N-acetyl-p-aminophenol, or paracetamol is an an-algesic
compound that is regularly used to relieve headache, backache, arthritis and
post-operative pain. This compound reduces fever associ-ated with bacterial
and viral infections [1]. Acetaminophen is a popular analgesic and antipyretic
medication which has few side effects and little toxicity if it is used in its
recommended doses [2], while over-dose of acetaminophen may be toxic and
results in sever side effects [3]. Its ready access has resulted in its increased
use in attempted sui-cide [4]. Consequently, in recent years different
techniques have been used for the determination of acetaminophen in a
variety of matrices including: titrimetry [5], UV–Vis spectrophotometry [6],
Fourier transformation infrared spectrophotometry [7], chromato-graphic
methods [8,9], mass spectrometry [10,11], fluorimetry [12] and the
amperometric method [2]. However, most of these methods are either time-
consuming or need sophisticated instruments. Com-pared with other options,
electrochemical techniques have inherent ad-vantages including: simplicity,
ease of miniaturization, high sensitivity and relatively low cost. Hence,
modified electrodes have been widely used for electrochemical determination
of different compounds be-cause modification of the electrode surfaces
significantly increases the sensitivity along with considerable decrease in
detection limit and in-terfering effects [4,13–31].
For catalytic purposes, modification of zeolites was, therefore, car-ried out
with some metals. Zeolites are crystalline microporous solids that contain
many channel-networks proving molecular-sized cages and passageways for
excellent steric control of reaction paths. The pore geometry is considered as
the main reason for the different activi-ties of zeolite-based catalysts.
Transition metal-containing zeolites were found to exhibit a high catalytic
activity [32–36]. Zeolite modified electrodes (ZMEs) display good sensitivity,
reproducibility, selectivity, durability, ion-exchange capacity, high thermal,
long life-time, low detection limit and high chemical stability [37–46]. As far
as we know, electrochemical detection of acetaminophen using zeo-lite
modified electrode (ZME) has not been reported. This article re-ports the
electrochemical behavior of Cobalt (II)-exchanged zeolite A incorporated in a
zeolite-modified carbon paste electrode for the electrochemical investigation
−1
of acetaminophen in a 0.4 mol L KCl solution. A simple electrode was
designed with a reservoir for holding the carbon-paste. The electrode surface
can be renewed very easily for a large number of times over a long period.
The influ-ences of several alkali ion electrolytes, pH, modifier percentage and
instrumental parameters on the response characteristics of the electrodes were
studied and the optimum operating conditions established. The modified
electrode was used for the electrocatalytic oxidation of acetaminophen using
cyclic voltammetry. The use of carbon-paste matrix, besides renewability by a
simple polishing, offers several other advantages including easy preparation,
uniform distribution of the catalyst into the paste, better reproducibility and
stability, very low Ohmic resistance and adequate robustness in aqueous
solutions [34].

Corresponding author.
E-mail address: arnezamzadeh@iaush.ac.ir (A. Nezamzadeh-Ejhieh).

http://dx.doi.org/10.1016/j.msec.2015.01.028 0928-
4931/© 2015 Elsevier B.V. All rights reserved.
494 L. Ahmadpour-Mobarakeh, A. Nezamzadeh-Ejhieh / Materials Science and Engineering C 49 (2015) 493–499

2. Experimental
2.1. Apparatus and chemicals
Zeolite A was synthesized from
waste porcelain (Esfahan glass
facto-ry, Isfahan, Iran). The
porcelain was ball-mill grounded,
and the parti-cles ≤1 mm in size
were sorted and washed with
distilled water. Characterization of
the waste porcelain used and the
method of the syn-thesis of zeolite
A were extensively described in our
previous work [45]. Graphite
powder, Nujol oil, cobalt nitrate and
other used salts with analytical
grade were obtained from Merck
(Purchased from Normal Labo Co.,
Isfahan, Iran). Pure acetaminophen
(99.99%, Aldrich) was obtained
from Kimia Gostar Pooyesh Co.
(Iran). Acetaminophen tablet (325
mg), acetaminophen–codeine table
(325 mg) and pediatric oral drops
were obtained from Hakim
pharmaceutical company (Tehran,
Iran). Adult cold tablet was
purchased from Abidi
pharmaceutical com-pany (Tehran,
Iran). Deionized distilled water was
used throughout the experiments.
Electrochemical experiments were
carried out using an EG&G Model
273 potentiostat/galvanostat
(PerkinElmer, USA) with
powersuite electrochemical
software. An Ag|AgCl|KCl (3 mol
−1
L ) electrode (Metrohm,
Switzerland) as reference electrode,
a platinum wire as the auxiliary
electrode and Co(II)-A/ZMCPE as
the working electrode were used. A
JENWAY 3505 pH meter (UK) was
used for pH adjustments. Square
wave voltammograms were
recorded using a Model
PGSTAT101
potentiostat/galvanostat (Metrohm,
Autolab B.V., Switzerland)
equipped with Nova 1.8 software.
2.2. Preparation of the modified
electrode
For ion exchange experiments,
about 1 g of zeolite Na–A was
lightly grounded and added to 25
−1
mL of 0.01 mol L tab-lets required for a suitable
Co(NO3)2·6H2O solution and the
obtained suspension was stirred for
24 h. In order to ensure full
exchange of Co(II) with zeolitic
+ carbon paste (CPE), unmodified Na-
Na , this process was repeated
another time using a fresh Co(II)
solution. Finally, the obtained
suspension was centrifuged and the
remaining solid was dispersed in
−1
dilute HCl (0.01 mol L ) for the
removal of the surface adherent
salts. The suspension was
centrifuged and the solid was again
dispersed in water and finally
centrifuged. The solid Co(II)-zeolite
A was air-dried and finally it was
used for the preparation of zeolite
modified carbon paste electrodes
(ZMCPEs) as follows: an
appropriate amount of the Co(II)-
exchanged zeolite (5–15 wt.% with
respect to graphite) was mixed with
100 mg graphite powder and then
Nujol was added. After thorough
hand mixing in a mortar (20 min) to
obtain a fine paste (provides
reproducible responses if solid
particles are homogeneously
dispersed into the paste), a portion
of the composite mixture was
packed into the end of a
polyethylene tube. Electrical contact
was made by forcing a copper wire
of ~ 1 mm diameter, positioned into
a glass tube with 2 mm diameter,
down the polyethylene tube and into
back of the paste. Unmodified
electrode was prepared in a similar
way, using a carbon-paste with
unmodified zeolite (Na-A). For
compar-ison, an unmodified raw
carbon paste electrode (CPE) was
also prepared in a similar method. A
typical schematic diagram for the
pre-pared electrodes was shown in
our previous work [40]. The
electrode surface was polished
using a soft paper and then rinsed
with ethanol and distilled water,
respectively. All the electrochemical
experiments were carried out under
pure nitrogen atmosphere at room
temperature.
2.3. Real sample preparation
Some commercial
pharmaceutical samples including
acetamino-phen tablet (325 mg),
acetaminophen–codeine table (325
mg), pediat-ric oral drops and adult
cold tablet were used for the
determination of their
acetaminophen contents. An
adequate amount of each tablet was
finely powdered in a mortar with
pestle. Calculated amounts of the
concentration were separately
transferred into a 100 mL
volumetric flask and dissolved in
0.4 mol L
−1
KCl solution
(pH 3.0). The content of the flask
was sonicated for 5 min to complete
dissolution. Finally, the solutions
were filtered and the cleared
solutions stored in refrigerator for
further uses.
2.4. Procedure
For cyclic voltammetric
experiments, 25 mL supporting
electrolyte solution was pipetted
into the electrochemical cell and
deaerated by purging with high
purity nitrogen gas for 5 min. The
inert gas was passed over the
solution during all the voltammetric
measurements. The modified
electrode together with the
reference and the counter electrodes
were immersed into the solution and
after several pre-liminary scans; the
potential was scanned from + 1.4 to
−0.5 V vs. Ag/AgCl reference
electrode using cyclic voltammetry.
Then different volumes of
acetaminophen solution were added
to the voltammetric cell and the
potential was scanned from + 1.4 to
−0.5 V vs. Ag/AgCl. All
electrochemical measurements were
conducted at room tempera-ture (25
°C). The modified electrode was
kept in open air when not in use. In
all studies, after renewing the
electrode surface by simple
polishing and reusing the electrode,
the response of the electrode was
improved with increasing the
repetitive scans and the best
response was obtained at the 10th
scan. Hence, in all experiments this
was re-corded as the best
voltammogram.
3. Results and discussion
3.1. Electrochemical behavior of
Co(II)-A/ZMCPE (in the absence of
acetaminophen)
In preliminary studies, the effect
of the modifier on the voltammetric
behavior of the electrode was
investigated because voltammetric
response of ZMEs extremely relates
to the nature of electroactive com-
ponents incorporated in zeolite
structure. Hence, it would be
expected that Na-A/CPE electrode
does not show a voltammetric
response in supporting electrolyte
solution. To confirm this postulate,
voltammetric behavior of the raw
A carbon paste (UCPE) and the
zeolite Co(II)-A modified carbon
paste electrode (Co(II)-A/ZMCPE)
−1
was investigated in 0.1 mol L KCl
solution at a potential scan rate of
−1
50 mV s . Fig. 1A shows the
resulting voltam-mograms, recorded
after several preliminary scans. As
shown, no voltammetric response
was observed for CPE (Fig. 1A-a)
and UCPE (Fig. 1A-b). This shows
that when ion exchange process
takes place between non-
+
electroactive Na zeolite framework
+ +
and solution K cations, Na cannot
produce any voltammetric response
at the elec-trode surface. These
observations have good agreement
with the literature which shows that
ZMEs containing alkaline and
alkaline earth cations do not
produce any voltammetric responses
in an electro-lyte solution [40].
From Fig. 1, it is obvious that a
well-defined peak was observed
only for the Co(II)-A-modified
electrode (Fig. 1A–d). It can be
described on the basis of possible
mechanisms for the electrochemical
processes at zeolite-modified
electrodes. The electrochemical
techniques are useful methods to
study the diffusion of cations in
zeolites. On the other hand, the
electrochemistry involves
heterogeneous chemical phenome-
na which occur heterogeneously on
the electrode at the electrode–
solution interface [46].
In general, three possible
mechanisms including: extra-zeolite
elec-tron transfer, intra-zeolite
electron transfer and boundary
associated species or ‘topological
redox isomers’ have been described
for ZMEs [38,47]. In a typical
extra-zeolite electron transfer
mechanism (the mechanism
describes the behavior of the
electrode in this work), the redox
species were first ion-
exchanged by the
supporting electrolyte
cations and then diffuse to a
conducting part of the
electrode surface to
undergo charge transfer. To
investigate reaction
mechanism, the effect of
supporting electrolyte on
voltammetric response of
the elec-trode was studied.
L. Ahmadpour-Mobarakeh, A. Nezamzadeh-Ejhieh / Materials Science and Engineering C 49 (2015) 493–499 495

of definite pore size of zeolites, ion exchange property of zeolites is ex-

tremely related to the nature of electrolyte cations [34,37–40,47]. Hence,
voltammetric response of the Co(II)-A/ZMCP electrode was studied in
various electrolytes of which results are shown in Fig. 1B.
The selectivity of zeolite is mainly dependent on the solvated ionic size
and charge of the probe ions. Generally, cations with a higher charge and
smaller solvated radii (or higher charge density) are prefer-able for a given
+ +
zeolite [48]. Small cations of the external electrolyte, such as Na and K
enter to the structure of the zeolite to counterbal-ance the surplus negative
charge of the framework of the zeolite [49]. Therefore, the cyclic
voltammetric behavior of Co(II)-A/ZMCPE in KCl and NaNO 3 solutions is
2+ 2+
different from that obtained in CaCl 2 and MgCl2 solutions. Ca and Mg
cations with larger hydrated ionic radii could hardly pass into the cages of the
2+ 2+
zeolite. Therefore, in solu-tion containing Ca and Mg ions, lesser ion
exchange takes place and hence Co(II)-A/ZMCPE shows smaller
+
voltammetric currents. Among various alkali cations, K could easily
penetrate into the crystal-line lattice of the zeolite and exhibits higher peak
current than the others (Fig. 1B-c).

The effect of concentration of KCl as the best supporting electrolyte on

the voltammetric response of the modified electrode was investigat-ed and
corresponding voltammograms are shown in Fig. 1C. The results indicate that
the peak height was increased by increasing in KCl concen-tration from 0.1 to
−1 −1
0.5 mol L KCl. Although, a 0.5 mol L KCl solution showed a sharper
−1
cathodic wave, to prevent material consuming, a 0.4 mol L KCl solution
was selected as a supporting electrolyte for the next studies. Based on the
results presented in Fig. 1A to C, and the results of previous works [34,38],
the transfer mechanism is in con-formity with the extra-zeolite electron-
transfer mechanism as follows:
þ þ ð1Þ
CoðIIÞð zÞ þ 2C ðsÞ ⇆ CoðIIÞð i Þ þ 2C ð zÞ
− ð2Þ
CoðIIÞð iÞ þ e ⇆ Co ðIÞð iÞ:
 +
C is an electrolyte cation and the descriptors z, s and i stand for
zeolite, solution and zeolite–solution interface, respectively.

According to these reactions, first, the Co(II) electroactive species were

+
exchanged by K electrolyte cations (Eq. (1)) and then a charge transfer
occurred at the electrode/solution interface (Eq. (2)).
As shown in Fig. 1A (e, c and d) and Fig. 1B–C, another weaker cathodic
peak was also observed at more negative potentials. We sug-gest two
following mechanisms for this peak. In the first mechanism, the obtained
Co(I) from the first step was reduced to Co(0) according to the following
mechanism:
−
CoðIÞð i Þ þ e ⇄ Coð0Þði Þ: ð3Þ

The decrease in this peak current can be related to the diffusion of the
obtained Co(I) species from the electrode surface to the bulk solution.
−1
Fig. 1. (A): Cyclic voltammograms obtained in 0.1 mol L KCl for the (a) CPE, (b) UCPE,
(c) ZME with modifier concentration of 5%, (d) ZME with modifier concentration of 10% and The second mechanism can be suggested as an intra-zeolite mecha-nism
−1
(e) ZME with modifier concentration of 15% at a scan rate 50 mV s ; (B): cyclic volt-
ammograms for the redox reaction of Co(II)-A/ZMCPE in different supporting electrolytes:
as follows:
−1 −1 −1 −1
(a) 0.1 mol L MgCl2, (b) 0.1 mol L NaCl, (c) 0.1 mol L KCl and (d) 0.1 mol L CaCl2; − þ þ
(C): cyclic voltammograms for the redox of Co(II)-A/ZMCPE in different concentrations of CoðIIÞð zÞ þ 2e þ 2K ði Þ ⇆ Coð0Þði Þ þ K ð zÞ: ð4Þ
−1 −1 −1 −1
KCl solution: (a) 0.1 mol L KCl, (b) 0.2 mol L KCl, (c) 0.3 mol L KCl, (d) 0.4 mol L
−1
KCl and (e) 0.5 mol L KCl.
3.3. Effect of electrode composition

3.2. Effect of supporting electrolyte on the voltammetric response of the
Co(II)-A-modified electrode
The effect of supporting electrolyte on voltammetric response of the
electrode was studied because the ion exchange process has a major role in
voltammetric response of ZMEs [34,37–40]. In addition, because
The modified paste ingredient is also an important parameter which affects
the electrochemical response of all modified electrodes specially ZMEs. This
affects on the resistance of the proposed electrode and can also bring
sufficient amount of the modifier to reach a suitable redox re-action. In ZMEs,
presence sufficient amount of the modifier significantly increases the ion-
exchange extent which in turn reach sufficient
496 L. Ahmadpour-Mobarakeh, A. Nezamzadeh-Ejhieh / Materials Science and Engineering C 49 (2015) 493–499

amount of the electroactive species
on the electrode–solution interface.
Thus voltammetric current
significantly increases. For this
purpose, voltammetric responses of
some modified electrodes
containing 5, 10 and 15% (w/w) of
Co(II)-A were examined and the
results are presented in Fig. 1.
Based on the results the best
response was obtained for the
modified electrode containing 10%
of the modifier (Fig. 1A-d). On the
other hand, low amounts of the
modifier can decrease the extent of
ion exchange, while high amounts
increased the resistance of the
electrode; both of which decrease
peak currents [40]. However, a
well-defined oxi-dation peak with a
peak potential at 0.96 V was
observed for the Co(II)-A-modified
electrode with modifier
concentration of 10% in the
−1
presence of 0.1 mol L KCl
−1
solution and ν = 50 mV s (Fig.
1A-d).
3.4. Effect of scan rate on the peak
current (in absence of
acetaminophen)
Fig. 2A shows cyclic
voltammograms of the Co(II)-
A/ZMCPE as a function of varying
scan rates in a 0.4 mol L KCl
−1
solution. Stability of the Co(II)-
A/ZMCPE was long, so that the
current response remained al-most
unchanged after several
determinations, during which the
elec-trode was stored in air. It can
be seen that the redox peak currents
for
Fig. 2. (A): Cyclic voltammograms of
Co(II)-A/ZMCPE with different scan rates
−1
in 0.4 mol L KCl. (a) 10, (b) 20, (c) 50, (d)
80, (e) 100, (f) 150, (g) 200, (h) 250, (i) 300,
−1
(j) 350 and (k) 400 mV s (inset: the plot of
Ep versus log ν); (B): cyclic voltammograms
at (a) CPE in presence of acetaminophen, (b)
UCPE in presence of acetaminophen,
(c) Co(II)-A/ZMCPE in blank solution, (d)
Co(II)-A/ZMCPE in presence of
−1
acetaminophen (1 μmol L ) and (e) Co(II)-
A/ZMCPE in presence of acetaminophen
−1 −1
(0.001 mol L ), scan rate 100 mV s ,
−1
supporting electrolyte 0.4 mol L KCl.
voltammetric behavior of
Co(II)/Co(I) system were linearly acetaminophen. Preliminary
increased with the increase of the experiments showed that this
scan rate, confirming that the redox electrode has better voltammetric
reaction is a diffusion controlled cur-rent in the presence of
process. As shown in Fig. 2A the acetaminophen. Hence, the behavior
oxidation and reduction peaks were of the elec-trode for the
re-spectively shifted to more electrochemical redox of
positive and more negative values. acetaminophen was studied in more
The scan rate and the peak
details. Under the same
potentials were linearly dependent
experimental conditions, the direct
to the log of scan rate when Ep N oxida-tion of acetaminophen at
200/n, which actually agrees with
UCPE (Fig. 2B-b) and CPE (Fig.
Laviron's theory [50]. According to 2B-a) showed relatively weak
this theory, linear potential sweep
peaks. Acetaminophen species at
voltammetry ap-pears as a
these electrodes is electro-inactive
convenient method for the
determination of the characteris-tics in the selected potential range and
the applied condi-tions. For the
(transfer coefficient and rate
constant) of the electrochemical Co(II)-A/ZMCPE, no cobalt species
reaction systems. For Co(II)- is initially present at the electrode
A/ZMCPE the peak-to-peak surface, because of the washing of
separation potential ( Ep = Epa − the Co(II)-A with dilute HCl and
deionized water to remove the
Epc) of the cyclic voltammogram
surface adsorbed species. How-ever,
recorded, was a maximum at 50 mV
−1 ion exchange occurs between the
in the presence of 0.4 mol L KCl.
intra-zeolite Co(II) ions and the
Laviron equations are summarized
electrolyte cations in the
below:
electrolytes with small cations. This
ion exchange process cause the
o transportation of Co(II) to the
Epa ¼ E þ A ln ½ ð1−αÞ=m&
ð5Þ electrode sur-face. Electrochemical
reactions are complex and different
o
Epc ¼ E þ B ln½α=m& mechanism could be purposed for
ð6Þ w:
where:
þ þ
CoðIIÞð zÞ þ 2C ðsÞ ⇆ CoðIIÞð i Þ þ 2C ð zÞ
A ¼ RT=ð1−αÞnF; B ¼ RT=αn F
and m ¼ ðRT= FÞðKs=nνÞ: −
CoðIIÞð iÞ þ e ⇆ Co ðIÞð iÞ
ð7Þ
and we suggest:
From these expressions, it is
possible to determine the transfer CoðIIÞð iÞ þ C8H9NO2 ⇆ CoðIIÞ−C8H9NO2 ð i
coef-ficient (α) by measuring the
variation of the peak potentials with
−
scan rate (ν). A plot of Ep versus log CoðIIÞ−C8H9NO2 ð iÞ þ e ⇆ CoðIÞ−C8H9NO2
ν yields two straight lines with
slopes equal to 2.3RT/αnF and is an electrolyte cation and the descript
2.3RT/(1 − α)nF for the cathodic C+
and anodic peaks, respectively. The zeolite, solution and zeolite–solution
inset of Fig. 2A shows the plot of Ep respectively.
versus log ν with slopes equal to
0.219 (line equation: y = 0.245 +
2
0.219x, r = 0.9864, r = 0.9932) and
−0.373 (line equation: y = 1.434 −
2
0.373x, r = 0.9739, r = 0.9869) for
anodic and cathodic peaks,
respectively. Using the slopes of the
plots, the values of α and Ks were
respectively ob-tained as: 0.73 and
−1
0.44 s (the electron transfer
number is 1).
3.5. Electro-oxidation of
acetaminophen at the Co(II)-
A/ZMCPE
After the optimization of some
key operating factors on the
voltammetric behavior of the
Co(II)-A/ZMCPE, this electrode
was used for studding the
L. Ahmadpour-Mobarakeh, A. Nezamzadeh-Ejhieh / Materials Science and Engineering C 49 (2015) 493–499 497

According to Fig. 2B, the
formation of a complex between
acetamin-ophen and Co(II) can be
suggested. This hypothesis can be
confirmed by a negative shift in
cathodic peak potential along with
the increase in the peak current in
the presence of acetaminophen (and
also with the in-crease in its
concentration). In this case,
regarding Eqs. (8) and (10), more
Co(II) species came out from the
zeolite channels and hence an in-
crease in peak current was observed
according to Eq. (11).
Higher concentrations
acetaminophen significantly
increased the second cathodic peak
current (Fig. 2B-e). In this
condition, more Co(I)–C8H9NO2
complex species were formed and
their diffu-sion to solution bulk was
reduced due to increase in the
viscosity of the solution. The
reduction of the Co(I)–C8H9NO2
species is shown by the following
equation:
−
CoðIÞ−C8H9NO2ði Þ þ e ⇆ Co ð0Þ− process takes place easier. We sug-
In the case of large encapsulated
species (organic species or organo-
metallic complexes physically
entrapped in the zeolite cages), the with cobalt cations, a decrease in
intensity of the electrochemical
response was often lower and
mostly accepted to be due to
boundary associated redox probes
[51,52]. They often display distinct decrease in the peak current.
voltammetric signals that might be
useful to distinguish redox species
associated with different sites in/on peak current to pH 2 (to prevent the
the alu-minosilicate as well as
conformational changes upon
immobilization in zeolite cages
[53,54].
3.6. Effect of pH on the peak
current
The pH of the investigated
environment is an important
parameter which affects on the
voltammetric behavior of the
electrode especially for investigated
analytes containing acidic or basic
functional groups. The stability of
these analytes also depends on
solution pH. For ZME
investigations, the pH of the
environment extensively affects on
the ion-exchange extent. To
investigate these effects, the effect
of the pH on the voltammetric
behavior of the proposed electrode
over the pH range of 2.0–10.9 was
investigated and the results are
presented in Fig. 3A. The cathodic
peak currents were affected by pH
and significantly decreased by
raising the pH. This can be related
to the cooperation of hydronium ion
in displacing Co(II) from zeolite
pores. In our study, the highest
sensitivity was observed at pH 2
and 3. In this pH range, although
protonation of the functional groups
of acetaminophen causes a decrease
in complex formation and hence
peak current, but ion exchange was
extremely increased due to higher
concentration and smaller radii of
hydronium ion. The latter case in
of turn causes a signifi-cant increase in
the peak current. According to the
obtained results, increase in ion
exchange extent is a predominant
process.
+ tyrosine, and amoxicillin hydrate
Since H ion is one of the by-
products formed in the oxidation of
acetaminophen, at lower pHs the
+
high concentration of H hinders the
oxidation of acetaminophen due to
common ion effect [14–17]. But at
more alkaline pH values this
gest at higher pHs acetaminophen
may be oxidized by the probably
present impurities in the solution.
Since the oxidized form cannot im-
part in the complexation process
peak current was observed. In
addition, at more alkaline pHs
Co(II) can be precipitated as
hydroxide which in turn causes a
Therefore, pH 3.0 with near
probable decomposition of the
zeolite at high acidic solutions) (ipc)
was selected as the optimized pH
for the determination of acetamino-
phen in the next experiments.
3.7. Effect of scan rate on the peak
current in the presence of
acetaminophen
The effect of scan rate on the
peak current was investigated in the
−1
presence of 0.001 mol L
acetaminophen and the obtained CV
voltam-mograms are shown in Fig.
3B. This figure exhibited the strong
depen-dence of the CV behavior of
the electrode on the potential scan
rates
The experimental results
−1
indicate that, ν = 100 mV s
creates suit-able conditions for
continuing our experiments.
3.8. Interference studies
The effect of various
compounds in the determination of
acetamino-phen was studied by
applying the method of mixed
solutions when the developed
procedure was exploded for the
−1
determination of 1 μmol L
acetaminophen under the optimum
conditions (Table 1). The tolerance
limits, given in Table 1, are the
molar ratio of
acetaminophen/interfer-ence. It was
found that several organic
compounds including D-lactose
monohydrate, L-tryptophan,
have no
Fig. 3. (A): Effect of pH on the cyclic
voltammetric peak height for the
determination of acetaminophen at the
−1
Co(II)-A/ZMCPE, scan rate 100 mV s , in
−1
the presence of 0.001 mol L
−1
acetaminophen and 0.4 mol L KCl; (B):
cyclic voltammograms of the Co(II)-
A/ZMCPE in the presence of 0.001 mol L
−1
−1
acetaminophen, 0.4 mol L KCl and pH 3.0
at different scan rates: (a) 20, (b) 50, (c) 80,
(d) 100, (e) 150, (f) 200, (g) 300 and (h) 400
−1
mV s (inset: linear curve of cathodic peak
current with the square root of scan rate).
so increasing the scan rates
increased peak current especially
for the first cathodic peak. By
increasing the scan rate, before the
diffusion of the Co(II)-complex to
the bulk solution, it undergoes a
reduction pro-cess at the electrode
surface and hence a significant
increase in the peak current was
observed.
The inset of Fig. 3B shows that
the first cathodic peak current was
linearly increased with the square
root of the scan rate that ranged
from 20.0 to 400.0 mV s , and it
−1
can be expressed as follows:
1=2 2
ipcðμAÞ ¼ 12:44ν þ 1:60 r ¼ 0:9548
498 L. Ahmadpour-Mobarakeh, A. Nezamzadeh-Ejhieh / Materials Science and Engineering C 49 (2015) 493–499
 2+ b
Ca tablet
3+ c
Fe 3 Adult cold 325 296.73 ±
effect even when their concentration 3+ Pharmacopoeia [55]. The results are d
Al 4 Pediatric oral drop 100 mg/mL 104.98 ±
exceeds ~100 fold of acetamino- shown in Table 2, which are compa- a, b, c
phen. Some of the metal ions such Cd2+ from Hakim pharmacy, Tehran, Iran,
Ni2+ rable with those obtained by the d
from Abidi pharmacy, Tehran, Iran.
2+ 2+ 2+
as Cd , Ni and Cu have no ef- Cu
2+
proposed CV method, confirming
fect at concentration of about 60 Zn
2+
the efficiency of the proposed Analytical characteristics for
2+ Determination of acetaminophen in drug samplesmethod
by the Co(II)-A/ZMCPE determination of acetaminophen at
fold of acetaminophen. Fe for the analysis of
several reported methods
interferes in the determination if its acetaminophen tablets and drops.
concentration is as same as No. Sample Added
As can be seen, the results are in
acetaminophen, which can be (μmol L
−1 Electrode type Technique LDR (μmol L
good agreement with those of
related to the formation of a 1 Acetaminophen tablet 0.00 labeled in the formulation, and CdPCNF/GCE AMP
a 1.64–52.90
relatively strong complex with 2 8.27 satisfactory recoveries were CoHCF DPV
b 3.33–1000
acetaminophen. 3 23.04 f-MWCNTs/GCE DPV 3–300
4 Acetaminophen 0.00
obtained. The statistical ‘t-test’ was
PAY/nano-TiO2/GC CV 12–120
5 codeine tablet 8.27 used for comparison of aver-ages SWCNT/CCE DPV 0.2–150
6 23.04 and the results confirmed that PANI–MWCNTs SWV
c 1–100
3.9. Real sample analysis and 7 Adult cold tablet 0.00 random errors affect the result due 250–2000
analytical application 8 8.27 NaMM/GCE d 0.33–1.65
to less calculated t-values than its SWSV
9 23.04 CNPs/GCE DPV 0.1–100
As a practical point of view, the 10 Pediatric oral drops 0.00 critical value of t0.05,6 = 2.31 [56]. MWCNTs:graphite/GC SWV 0.47–1302
proposed method was also used in 11 25.44 The results show that this method CNTPE CV 0.15–126
12 70.87 has good selectivity and sensi-tivity C-Ni/GCE CV & DPV 7.8–1100
the determination of acetaminophen
a for acetaminophen in drug samples. GO film/GCE CV 0.00013–26.5
in some commercial pharmaceuti- Average of five replicate measurements. MWCNT-ACS/GCE CV 0.05–2
cal samples including MWNT-film/GCE Choronoamp. 5–100
acetaminophen tablet (325 mg), AMP SAMs/AU CV & SWV 2–4000
acetaminophen– codeine table (325 3.10. Performance of the system for CNT modified SPCE FID 2.5–1000
acetaminophen measurements Cu-Poly-TTCA CV & AMP 20−5000
mg), pediatric oral drop and adult
ZrO2−PEI/GCE AMP 19.6–2550
cold tablet. The concentration of
Best performance was achieved Co(II)-A/ZMCPE CV 0.5–80.6
acetaminophen was calculated using −1
in 0.4 mol L KCl and 0.001 mol a b
the standard ad-dition method in Amperometry, differential pulse
−1
order to prevent any matrix effects. L acetaminophen at pH 3.0 and voltammetry,
c
square-wave
To evaluate the ap-plicability of the 10% modifier with a scan rate of d
voltammetry, square wave stripping
−1 voltammetry
proposed method, the recovery of 100 mV s . Since the cathodic
acetaminophen was also determined peak was proportional to the
in various drug samples. concentration of acetaminophen,
Satisfactory results given in Table 1 this peak can be used for the deter-
confirm good applicability of the mination of acetaminophen. Due to
proposed electrode for the de- the higher sensitivity of square
termination of acetaminophen in wave voltammetry (SqW) with
respect to CV, SqW was used for
real samples.
quanti-tative determination of
The tablets were also analyzed acetaminophen at the optimized
using the standard method conditions (PH/PW = 0.25 ms, SH =
according to the official UV −1
2.0 mV and ν = 100.0 mV s ). Fig.
spectrophotometric method 4 shows that the cathodic peak
described in British current was linearly dependent on
the acetamino-phen concentration
−1
Table 1 over the range of 0.1–190 μmol L
Results of interference and recovery studies. with correlation coefficient of r =
2
Interference data for 0.9989 (r = 0.9979, n = 10) (RSD%
determination of 1 μmol = 2.5%) and detec-tion limit of 0.04
−1
L acetaminophen with −1
Co(II)-A/ZMCPE (n = 3) μmol L which can be expressed as
Interfering species follows:
D-Lactose monohydrate ipcðμAÞ ¼ 7:43 CAC þ 7:40:
L-Tryptophan

Tyrosine
Long term stability was
Amoxicillin hydrate
Cysteine investigated by taking the response
L-Serine of the modified electrode in a period
Citric acid of 9 months. The electrode was
L-Ascorbic acid stored
Uric acid
L-Histidine
L-Glycine Table 2
BrO3
− Real sample analysis and analytical
2− characteristics of the electrode.
Cr2O7
2−
CO3 Determination of acetaminophen in drug
2−
SO4 samples (t0.05,6 = 2.31)
−
NO3 No Real sample Amount of acetaminophen mg/tablet
−
ClO4
+
Li Label
2+
Be a
2+ 1 Acetaminophen tablet 325
Mg
2 Acetaminophen codeine 325
L. Ahmadpour-Mobarakeh, A. Nezamzadeh-Ejhieh / Materials Science and Engineering C 49 (2015) 493–499 499

Fig. 4. Calibration linear curve for the
determination of acetaminophen based on
first re-duction peak current at the optimum
−1
conditions, pH 3.0, scan rate 100 mV s
(inset: the raw voltammograms of redox
reactions).
in open air when not in use.
Voltammetric measurements and
calibra-tion were performed every
three days during the first month
and then every week for the rest of
the period. The electrode retained
its full ac-tivity during this period; it
was only necessary to renew the
surface by a slight rubbing of the
electrode on a soft paper, whenever
the electrode response diminished.
The validity of the results was
investigated by “g” value statistical
testing, or a g-test [56], using the
following equation:
2 [14] S.J.R. Prabakar, S.S. Narayanan,
largest s
g¼
2 2 2 2
s 1þs 2þs 3þs 4
2 Actuators B 146 (2010) 314.
where s i is the variance of each
class of determinations. The
calculated g value was 0.0814,
which is less than the critical value
of g0.05,5,20 = 0.2288 (5 replicates
per 20 classes) [56].
The reproducibility of the
voltammetric response of the
modified electrode was investigated
by carrying the measurements on
four inde-pendent electrodes with
the same composition. The relative
standard deviation (between
electrode variation) was less than
2%. The relative standard deviations
of 5 replicate measurements
performed on a single electrode
(within electrode variation) at
several acetaminophen con-
−1
centrations of 0.001 mol L were
less than 1.5%. In the
reproducibility investigation, the
validity of the obtained results was
also tested by g-test. The calculated
g value was 0.4168, which is less
than the critical value of g0.05,5,4 =
0.7212 [56]. The good electrode
repeatability and re-producibility
indicate that the pastes are
homogeneous.
For comparison, the most
important reported electrochemical
methods for the determination of
acetaminophen are summarized in
Table 2. The results showed that
Co(II)-A/ZMCPE is suitable for
sensitive and selective
determination of acetaminophen.
4. Conclusions
Ion exchange property of
zeolites takes place easily when a
cobalt(II)-exchanged zeolite A was
incorporated into the carbon paste
matrix con-structing a zeolite
modified electrode. The charge and
size selectivity properties of zeolites
were also retained in this matrix
with regard to the dependence of
voltammetric behavior of the
proposed electrode to the nature and
concentration of different
supporting electrolytes. Because
Dinarvand, Electrochim. Acta 55
(2010) 2752.
of the dependence of the [25] S. Shahrokhian, E. Asadian,
voltammetric response of the Electrochim. Acta 55 (2010) 666.
modified elec-trode to concentration [26] E. Molaakbari, A. Mostafavi, H.
Beitollahi, R. Alizadeh, Analyst 139
of acetaminophen, this electrode (2014) 4356.
was used for the determination of [27] Q. Wan, X. Wang, F. Yu, X. Wang, N.
Yang, J. Appl. Electrochem. 39 (2009)
this material in the solution and
1145.
common pharma-ceutical samples. [28] H. Beitollahi, I. Sheikhshoaie, 56
Statistical g-test showed that the (2011) 10259.
random errors affect the [29] P. Fanjul-Bolado, P. Lamas-Ardisana,
D. Hernandez-Santos, A. Costa-Garcia,
determinations. Long term stability, Anal. Chim. Acta. 638 (2009) 133.
high sensitivity, low detection limit, [30] H.M. Moghaddam, H. Beitollahi, Int.
relative wide dynamic range, easy J. Electrochem. Sci. 6 (2011) 6503.
[31] V. Sima, C. Cristea, F. Lapadus, I.O.
preparation, relatively high Marian, A. Marian, R. Sandulescu, J.
selectivity, and easy regeneration by Pharm. Biomed. Anal. 48 (2008)
a simple polishing of the electrode 1195.
[32] A. Nezamzadeh-Ejhieh, N. Moazzeni,
surface, make it a useful device for J. Ind. Eng. Chem. 19 (2013) 1433.
the determination of acetaminophen [33] S. Sohrabnezhad, A. Pourahmad, M.A.
Zanjanchi, J. Iran. Chem. Soc. 6
in different samples. (2009) 612.
[34] A. Nezamzadeh, M.K. Amini, H.
Faghihian, Int. J. Electrochem. Sci. 2
(2007) 583.
References [35] A. Nezamzadeh-Ejhieh, M. Karimi-
Shamsabadi, Chem. Eng. J. 228 (2013)
[1] H. Razmi, Esmaeil Habibi, 631.
Electrochim. Acta 55 (2010) 8731.
[36] A. Nezamzadeh-Ejhieh, Z. Banan,
[2] J.T. Afshari, T.Z. Liu, Anal. Chim. Iran. J. Catal. 2 (2) (2012) 77.
Acta. 443 (2001) 165. [37] A. Nezamzadeh-Ejhieh, E. Mirzaeyan,
[3] M. Mazloum-Ardakani, H. Beitollahi, Mater. Sci. Eng. C 33 (2013) 4751–
M.K. Amini, F. Mirkhalaf, M. 4758.
Abdollahi-Alibeik, Sensors Actuators [38] A. Nezamzadeh-Ejhieh, H.-S.
B 151 (2010) 243. Hashemi, Talanta 88 (2012) 201.
[4] M. Boopathi, M.S. Won, Y.B. Shim, [39] M. Mazloum-Ardakani, Z. Taleat, H.
Anal. Chim. Acta. 512 (2004) 191. Beitollahi, H. Naeimi, J. Iran. Chem.
[5] K.G. Kumar, R. Leth, J. Pharm. Soc. 7 (2010) 251.
Biomed. Anal. 15 (1997) 1725. [40] A. Nezamzadeh–Ejhieh, M.
[6] S.D. Cekic, H. Filik, R. Apak, Anal. Shahanshahi, J. Ind. Eng. Chem. 19
Chem. 60 (2005) 1147. (2013) 2026.
[7] M.L. Ramos, J.F. Tyson, D.J. Curran, [41] B. Haghighi, M. Khosravi, A. Barati,
Anal. Chim. Acta. 364 (1998) 107. Mater. Sci. Eng. C 40 (2014) 204.
[8] D.J. Speed, S.J. Dickson, E.R. Cairns, [42] A. Nezamzadeh–Ejhieh, N.
N.D. Kim, J. Anal. Toxicol. 25 (2001) Masoudipour, Anal. Chim. Acta. 658
198. (2010) 68.
[9] J.L. Perez, M.A. Bello, Talanta 48 [43] A. Nezamzadeh–Ejhieh, A.
(1999) 1199. Esmaeilian, Microporous Mesoporous
[10] Y. Zhang, N. Mehrotra, N.R. Budha, Mater. 147 (2012) 302.
M.L. Christensen, B. Meibohm, Clin.
Chim. Acta 398 (2008) 105. [44] M. Behpour, A. Valipour, M.
[11] J.M. Conley, S.J. Symes, S.A. Keshavarz, Mater. Sci. Eng. C 42
Kindelberger, S.M. Richards, J. (2014) 500.
Chromatogr. A 1185 (2008) 206. [45] A. Nezamzadeh–Ejhieh, E. Mirzaeyan,
[12] J. Vilchez, R. Blanc, R. Avidad, A. Electrochim. Acta 56 (2011) 7749.
Navalon, J. Pharm. Biomed. Anal. 13 [46] M. Ghaedi, S. Naderi, M.
(1995) 1119. Montazerozohori, R. Sahraei, A.
[13] H. Razmi, M. Harasi, J. Iran. Chem. Daneshfar, N. Taghavimoghadam,
Soc. 5 (2008) 296. Mater. Sci. Eng. C 32 (2012) 2274.
[47] A. Nezamzadeh–Ejhieh, Z.
Talanta 72 (2007) 1818. Nematollahi, Electrochim. Acta 56
[15] Z.A. Alothman, N. Bukhari, S.M. (2011) 8334.
Wabaidur, S. Haider, Sensors [48] C.B. Ahlers, J.B. Talbot, Electrochim.
Acta 45 (2000) 3379.
[16] S.A. Kumar, C.F. Tang, S.M. Chen, [49] Y.J. Li, C.Y. Liu, J. Electroanal. Chem.
Talanta 76 (2008) 997. 517 (2001) 117.
[17] B. Habibi, M. Jahanbakhshi, M.H. [50] E. Laviron, J. Electroanal. Chem. 101
Pournaghi-Azar, Anal. Biochem. 411 (1979) 19.
(2011) 167. [51] A. Domenech, P. Formentin, H.
[18] M. Li, L. Jing, Electrochim. Acta 52 Garcia, M.J. Sabater, J. Phys. Chem. B
(2007) 3250. 106 (2002) 574.
[19] B. Muralidharan, G. Gopu, C. Vedhi,
P. Manisankar, Appl. Clay Sci. 42 [52] A. Domenech, H. Garcia, M. Alvaro,
(2008) 206. E. Carbonell, J. Phys. Chem. B 107
[20] F. Ghorbani-Bidkorbeh, S. (2003) 3040.
Shahrokhian, A. Mohammadi, R. [53] R. Ganesan, B. Viswanathan, J. Phys.
Dinarvand, Electrochim. Acta 55 Chem. B 108 (2004) 7102.
(2010) 2752. [54] A. Domenech, H. Garcia, E. Carbonell,
[21] H. Beitollahi, M. Mostafavi, J. Electroanal. Chem. 577 (2005) 249.
Electroanalysis 26 (2014) 1090. [55] British Pharmacopoeia, London: Office
[22] M.H. Sheikh-Mohseni, A. of the British Pharmacopoeia
Nezamzadeh-Ejhieh, Electrochim. Commission, (1993) 483.
Acta 147 (2014) 572. [56] R.L. Anderson, Practical Statistics for
[23] M.M. Foroughi, H. Beitollahi, S. Analytical Chemists, Van Nostrand
Tajik, M. Hamzavi, H. Parvan, Int. J. Reinhold, New York, 1987.
Electrochem. Sci. 9 (2014) 2955.
[24] F. Ghorbani-Bidkorbeh, S.
Shahrokhian, A. Mohammadi, R.