Anal. Method Environ. Chem. J. 4 (1) (2021) 16-25  
Research Article, Issue 1  
Analytical Methods in Environmental Chemistry Journal  
Development of electrochemical sensor based on carbon  
paste electrode modied with ZnO nanoparticles for  
determination of chlorpheniramine maleate  
Hamideh Asadollahzadeh a,*  
aDepartment of Chemistry, Faculty of Science, Kerman branch, Islamic Azad University, Kerman, Iran, P. O. Box  
7635131167, Kerman, Iran  
A R T I C L E I N F O :  
Received 12 Dec 2020  
Revised form 3 Feb 2021  
Accepted 28 Feb 2021  
A B S T R A C T  
Zinc oxide (ZnO) nanoparticles with an average size of 60 nm have  
been successfully prepared by microwave irradiation. Carbon paste  
electrode (CPE) was modied with ZnO nanoparticles and used for  
the electrochemical oxidation of chlorpheniramine maleate (CPM).  
Cyclic voltammetry (CV) study of the modied electrode indicated  
that the oxidation potential shifted towards a lower potential by  
approximately 106 mV and the peak current was enhanced by 2 fold  
in comparison to the bare CPE (ZnO/CPE-CV). The electrochemical  
behaviour was further described by characterization studies of scan  
rate, pH and concentration of CPM. Under the optimal conditions  
the peak current was proportional to CPM concentration in the  
range of 8.0 ×10-7 to 1.0 × 10-3 mol L-1 with a detection limit of 5.0  
× 10-7 mol L-1 by differential pulse voltammetry (DPV). The peak  
current of CPM is linear in the concentration range of 0.8 - 1000  
μM (R2=0.998). The ZnO/CPE has a good reproducibility and high  
stability for the determination of CPM using this electrode. The  
proposed method was successfully applied to the determination of  
CPM in pharmaceutical samples. In addition, the important analytical  
parameters were compared with other methods which show that ZnO/  
CPE-CV procedure are comparable to recently reported methods.  
Available online 28 Mar 2021  
Chlorpheniramine maleate,  
Pharmaceutical determination,  
Carbon paste electrode,  
Cyclic voltammetry,  
ZnO nanoparticles  
antagonist has been used to treat allergies such  
1. Introduction  
as hay fever, and other respiratory tract allergies  
[1]. The common side effects of chlorpheniramine  
(CPM, CP) include sleepiness, restlessness, and  
weakness dry mouth and wheeziness. CPM/CP is  
often combined with phenylpropanolamine to form  
an allergy medication with both antihistamine and  
decongestant properties,CPM/CPisapartofaseriesof  
antihistamines including pheniramine (Naphcon).  
As previous work, the CPM/CP synthesized  
through pyridine based on alkylation by  
4-chlorophenylacetonitrile. The CPM generated by  
alkylating with 2-dimethylaminoethylchloride in  
Antihistamines are a class of drugs commonly used  
to treat symptoms of allergies. These drugs help  
treat conditions caused by too much histamine, a  
chemical created by your body’s immune system.  
Chlorpheniramine maleate [3-(4-chlorophenyl)-  
CPM] is an alkyl amine antihistamine. For  
more than 30 years, the CPM as a H1-receptor  
*Corresponding Author: Hamideh Asadollahzadeh  
CPE-ZnO nanoparticles for CPM determination  
Hamideh Asadollahzadeh  
Schema 1. Synthesis of CPM/CP based on alkylation by pyridine  
the presence of sodium amide (Schema 1). Several  
methods have been reported for the determination  
of CPM maleate including, spectrophotometry [2],  
liquid chromatography [3], liquid chromatography-  
performance liquid chromatography [6]. However,  
these instrumental methods have suffered some  
disadvantages such as time consuming, solvent-  
usage intensive and requires expensive devices  
and maintenance [7]. The electrochemical methods  
using chemically modied electrode have been  
widely used in sensitive and selective analytical  
methods for the detection of the trace amounts  
of biologically important compounds. Electrode  
surface may be changed with metal nanoparticles  
and such surfaces have found various applications  
within the sector of bio electrochemistry,  
particularly in biosensors. it’s also been observed  
that nanoparticles can act as conductivity centers  
facilitating the transfer of electrons. Additionally,  
they provide large catalytic area. Several types of  
nanoparticles, including metal nanoparticles [8-  
10], oxide nanoparticles [11-13], semiconductor  
nanoparticles and even composite nanoparticles  
[14-16] are widely utilized in electrochemical  
sensors and bio sensors [17]. Some electrochemical  
methods are also reported for the determination of  
CPM by voltammetry [18-21]. Electrochemical  
sensors satisfy many of the requirements for such  
tasks particularly owing to their inherent specicity,  
rapid response, sensitivity and simplicity of  
preparation [18]. To our knowledge, no study has  
reported the electrocatalytic oxidation of CPM by  
using ZnO modied carbon paste electrode. Thus,  
in the present work, the ZnO nanoparticle have been  
synthesized using microwave irradiation process  
and a modied carbon paste electrode is fabricated  
by using ZnO nanoparticles for the determination  
of CPM. All results were validated by spiking  
samples and compared to other methods.  
2. Experimental  
2.1. Chemicals and Reagents  
Pure CPM, sodium dihydrogen ortho phosphate  
(NaH2PO4), disodium hydrogen phosphate  
(Na2HPO4), sodium phosphate (Na3PO4),  
hydroxide (NaOH), hydrochloric acid (HCl),  
Zn(NO3)2.4H2O and graphite powder were  
obtained from Merck. The buffer solutions were  
prepared from orthophosphoric acid and its  
salts in the pH range of 8 to 11. All the aqueous  
solutions were prepared by using double distilled  
water. High viscosity paraffin (d =0.88 kg L1)  
from Merck was used as the pasting liquid for  
the preparation of the carbon paste electrodes.  
2.2. Apparatus  
Electrochemical studies were performed using  
a Metrohm polarograph potentiostat-galvanostat  
(Metrohm Computrace 797-VA). The 797 VA is a  
voltammetric measuring stand that is connected  
to a PC. The computer software provided controls  
the measurement, records the measured data and  
evaluates it. Operation is most straightforward  
due to the well-laid-out structure of the program.  
The integrated potentiostat with galvanostat  
guarantees the highest sensitivity with reduced  
noise. Voltammetry system for the determination  
of organic additives in electroplating baths with  
Anal. Method Environ. Chem. J. 4 (1) (2021) 16-25  
cyclic voltammetric stripping (CVS). Complete  
accessories with VA Computrace software and  
all electrodes for a complete measurement  
system: Rotating platinum disk electrode  
(RDE), Ag/AgCl reference electrode and Pt  
auxiliary electrode. Three-electrode system  
consisted of a bare CP and ZnO/CPE electrode  
as the working electrode, Ag/AgCl (3M KCl) as  
the reference electrode and a platinum wire as  
the auxiliary electrode. A Metrohm 691 pH/Ion  
meter was used for pH measurements. Solutions  
were degassed with nitrogen for ten minutes  
prior to recording of the voltammogram. X-ray  
diffraction (XRD) patterns were recorded by a  
Philips-X’pertpro, X-ray diffractometer using  
Ni-filtered Cu Ka radiation in University of  
Kashan-Iran. Scanning electron microscopy  
(SEM) images were obtained from LEO  
instrument model 1455VP.  
long). Electrical contact was made by forcing  
a copper wire down into the tube. When  
necessary, a new surface was obtained by  
pushing out an excess of paste and polishing  
it on weighing paper. Unmodified CPE was  
prepared in the same way without adding of  
ZnO nanoparticles.  
2.5. Procedure and sample preparation  
20 pieces of CPM tablet (Daro pakhsh. Iran) were  
powdered in a mortar. A portion equivalent to a stock  
solution of a concentration of about 0.01 M was  
accurately weighed and transferred into a 100 mL  
calibrated ask and completed to the volume with  
double distilled water. The contents of the ask were  
sonicated for 10 min to affect complete dissolution.  
aliquots of the clear supernatant liquid and diluting  
them with the phosphate buffer solutions. Also, 0.5 ml  
of an ampoule of CPM, according to its specications,  
each ml of which contains 10 mg of the drug, was  
placed in a 25 ml calibrated ask and completed with  
a buffer at pH=10 and voltammetry was performed  
on it. The differential pulse voltammograms (DPV)  
were recorded between 0.4 and 1.2 V. The oxidation  
peak current of CPM was measured. The parameters  
for DPV were pulse width of 0.05 s, pulse increment  
of 4 mV, pulse period of 0.2 s, pulse amplitude of 50  
mV and scan rate of 50 mVs-1.  
2.3. Synthesis of ZnO nanoparticles  
In this work, zinc acetate and graphene powders  
were used as the starting reagent. 0.41 mol  
of Zn(NO3)2.4H2O was dissolved in 50 ml of  
deionized water under vigorous stirring. 1 ml of  
NaOH (1 M) was then added dropwise to the  
solution. Afterward, the solution was exposed by  
microwave irradiation with different powers and  
times. The microwave oven followed a working  
cycle of 30 s on and 70 s off (30 % power). After  
reaction in microwave the samples were cooled  
to room temperature naturally. Precipitates were  
washed with deionized water and ethanol, and  
air-dried at room temperature.  
3. Results and discussion  
3.1. XRD analysis  
The phase type, crystal structure and purity of  
the product obtained are determined by the XRD  
method. The XRD pattern of the as obtained ZnO  
nanoparticles as sample number 1 was shown in  
Figure 1. Peaks in this pattern are reported in the  
range of 2Ɵ from 20 to 80 degrees. Patterns of  
the samples were indexed as a cubic phase. The  
XRD results proved the high crystallinity and  
purity of the products synthesized by microwave  
method. According to XRD data, the crystalline  
size (Dc) of ZnO nanoparticles can be determined  
by using Debye- Scherrer formula. The obtained  
average particle size was found to be 60 nm.  
2.4. Preparation of bare carbon paste  
electrode and modified carbon paste electrode  
The modified carbon paste electrode was  
prepared by hand mixing 0.1 g of ZnO  
nanoparticles with 0.9 g graphite powder with  
a mortar and pestle. Then paraffin was added  
to the above mixture and mixed for 30 min  
until a uniformly wetted paste was obtained.  
This paste was then packed into the end  
of a glass tube (ca. 3.35 mm i.d. and 10 cm  
CPE-ZnO nanoparticles for CPM determination  
Hamideh Asadollahzadeh  
Fig. 1. XRD patterns of ZnO nanoparticles sample 1  
3.2. Scanning electron microscopy  
the nucleation of the particles is increased, and  
since the particles have a very active surface,  
large and cohesive masses are obtained in all test  
conditions. Therefore, the sample prepared in 360  
W power and 4 min time due to the creation of  
nanoparticles in nanometer size according to the  
scale of images and homogeneous distribution  
is an optimized condition for time and power  
consumption to make ZnO nanoparticles. The  
produced ZnO nanoparticles have mean diameters  
of approximately 40-80 nm.  
In Figure 2 shows SEM image of ZnO powder  
obtained at 4 min and 360 W (sample no 1), at  
540 W (sample no 2) and 750 W (sample no 3). As  
can be seen from SEM images, at 360 power, the  
reaction is faster due to the generation of more free  
radicals in solution and increased heat production  
due to the rotation of these active species. The  
formed nanoparticles have relatively smaller sizes  
and better distribution. At 540 and 720 W, due to  
the very high energy produced in these powers,  
Fig. 2. SEM images of the ZnO nanoparticles for a) sample no. 1, b) sample no. 2, c) sample no. 3  
Anal. Method Environ. Chem. J. 4 (1) (2021) 16-25  
3.3. Electrochemical behavior of CPM at the  
3.4. Effect of pH  
The effect of pH of the solution on the  
electrochemical response of CPM was investigated  
from pH 8 to 11 (although lower pH was also  
examined in which the peak did not appear well).As  
can be seen in the Figure 4, with increasing pH, the  
anodic potential shifts to more negative potentials,  
which indicates better oxidation of the material  
at the electrode surface and the electrocatalytic  
effect. A linear relationship existed between the  
potential and pH in the range 8 to 11 (Fig. 5). The  
linear regression equation was E= -60.5pH+1582  
(R2=0.991). The slope of 59 mV/pH suggests that an  
equal number of protons and electrons are involved  
in the oxidation process. Also, with increasing pH,  
the peak current increases to 10 and at pH = 11,  
the current decreases, so pH = 10 is chosen as the  
optimal point.  
The electrochemical behavior of CPM has been  
studied in two electrodes. Cyclic voltammetry  
(CV) was applied to investigate the electrochemical  
behavior of 0.4 mM CPM in 0.1 M phosphate buffer  
at pH 10 with a bare CPE and ZnO/CPE. Figure  
3 shows the cyclic voltammograms in the CPE  
and ZnO/CPE electrode. As shown in this gure,  
in the presence of CPM, an irreversible oxidation  
peak at 1.093 V on the bare CPE attributed to the  
electrochemical oxidation of CPM. In the case of the  
ZnO /CPE, the oxidation peak of CPM decreased to  
0.987 V and the peak current increased by 2.0 times  
compared with that for the bare CPE. These results  
transfer at the electrode surface and improve the  
electrochemical performance accordingly.  
Fig. 3. Cyclic voltammograms of CPE and ZnO/CPE at presence of 0.4 mM CPM in 0.1  
phosphate buffer solution (pH 10) at scan rate 50 mVs-1  
CPE-ZnO nanoparticles for CPM determination  
Hamideh Asadollahzadeh  
Fig.4. a) Cyclic voltamogram of CPM at different pH b) Relationship between the peak potential of CPM and pH.  
Fig. 5. Cyclic voltammograms of ZnO/CPE in the presence of 0.2 mM of CPM in 0.1 phosphate  
buffer solution (pH 10) at different scan rates (from inner to outer): 30, 50, 70, 100, 130, 200  
and 300 mV s-1. Insets: b, peak current vs. square root of scan rate (v )