A simple sonochemical assisted synthesis of NiMoO4/chitosan nanocomposite for electrochemical sensing of amlodipine in pharmaceutical and serum samples

Article abstract of DOI:10.1016/j.ultsonch.2019.104827

In this investigation, a facile sonochemical route has been developed for the preparation of porous nickel molybdate nanosheets/chitosan nanocomposite (NiMoO₄/CHIT) by using ammonium molybdate and nickel(II) acetate tetrahydrate and as nickel and molybdate precursor, respectively (ultrasonic power 60 W/cm² and frequency 20 kHz). The ultrasonic based materials preparation as a fast, convenient and economical approach has been widely used to generate novel nanomaterials. Herein, we report an efficient voltammetric sensor for amlodipine drug by using porous nickel molybdate nanosheets/chitosan nanocomposite (NiMoO₄/CHIT). Its structure and properties were characterized by x-ray diffraction pattern, scanning electron microscope, transmission electron microscope, elemental analysis and mapping. The electrochemical studies are indicated the NiMoO₄/CHIT modified glassy carbon electrode (GCE) exhibited the good performance towards electrocatalytic sensing of amlodipine drug. Consequently, a linear correlation between the anodic peak current with sensor concentration 0.025–373.6 μM with a detection limit and sensitivity of 4.62 nM and 4.753 μA·μM^?1·cm^?2, respectively. A voltammetry based drug analysis was found to be high sensitive and reproducible, which able to detect nanomolar concentration. Furthermore, the fabricated electrochemical sensor was applied in drug and biological samples.

Full text of DOI:10.1016/j.ultsonch.2019.104827

Journal Pre-proofs
A Simple Sonochemical Assisted Synthesis of Porous NiMoO4/chitosan Nano-
composite for Electrochemical Sensing of Amlodipine in Pharmaceutical For-
mulation and Human Serum
Bih-Show Lou, Umamaheswari Rajaji, Shen-Ming Chen, Tse-Wei Chen
PII:
S1350-4177(19)31180-0
DOI:
https://doi.org/10.1016/j.ultsonch.2019.104827
ULTSON 104827
Reference:
Ultrasonics Sonochemistry
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27 September 2019
8 October 2019
11 October 2019
Please cite this article as: B-S. Lou, U. Rajaji, S-M. Chen, T-W. Chen, A Simple Sonochemical Assisted Synthesis
of Porous NiMoO4/chitosan Nanocomposite for Electrochemical Sensing of Amlodipine in Pharmaceutical
Formulation and Human Serum, Ultrasonics Sonochemistry (2019), doi: https://doi.org/10.1016/j.ultsonch.
2019.104827
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A Simple Sonochemical Assisted Synthesis of Porous NiMoO4/chitosan Nanocomposite for
Electrochemical Sensing of Amlodipine in Pharmaceutical Formulation and Human Serum
Bih-Show Loua,b, Umamaheswari Rajajic, Shen-Ming Chenc,*, Tse-Wei Chenc
aChemistry Division, Center for General Education, Chang Gung University, Taoyuan 333,
Taiwan.
bDepartment of Nuclear Medicine and Molecular Imaging Center, Chang Gung Memorial
Hospital, Taoyuan 333, Taiwan.
cDepartment of Chemical Engineering and Biotechnology, National Taipei University of
Technology, No. 1, Section 3, Chung-Hsiao East Road, Taipei 106, Taiwan, Republic of China.
Corresponding Author: *E-mail: smchen78@ms15.hinet.net (S-M Chen), Phone: +886-2270-
17147. Fax: +886-2270-25238.
Abstract
In this investigation, a facile sonochemical route has been developed for the preparation
of porous nickel molybdate nanosheets/chitosan nanocomposite (NiMoO4/CHIT) by using
ammonium molybdate and nickel(II) acetate tetrahydrate and as nickel and molybdate precursor,
respectively (ultrasonic power 60 W/cm2 and frequency 20 kHz). The ultrasonic based materials
preparation as a fast, convenient and economical approach has been widely used to generate
novel nanomaterials. Herein, we report an efficient voltammetric sensor for amlodipine drug by
using porous nickel molybdate nanosheets/chitosan nanocomposite (NiMoO4/CHIT). Its
structure and properties were characterized by x-ray diffraction pattern, scanning electron
1

microscope, transmission electron microscope, elemental analysis and mapping. The
electrochemical studies are indicated the NiMoO4/CHIT modified glassy carbon electrode (GCE)
exhibited the good performance towards electrocatalytic sensing of amlodipine drug.
Consequently, a linear correlation between the anodic peak current with sensor concentration
0.025 to 373.6 µM with a detection limit and sensitivity of 4.62 nM and 4.753 µA.µM-1.cm-2,
respectively. A voltammetry based drug analysis was found to be high sensitive and
reproducible, which able to detect nanomolar concentration. Furthermore, the fabricated
electrochemical sensor was applied in drug and biological samples.
Keywords: Sonochemical synthesis; Bimetal oxide; Electrochemical detection; Drug analysis;
Biological samples.
1. Introduction
Amlodipine is a dihydropyridine type drug, which inhibits the several disease such as high
blood pressure and coronary artery disease in human and animal [1-4]. So, it has been widely
used to treat hypertension; due to its relatively low cost and strong effective [5-7]. However, an
excessive intake of amlodipine has side effects in form of abdominal pain, swelling, feeling tired,
and nausea [8-11]. Therefore, it is necessary to develop rapid and effective method to determine
the level of amlodipine in biological system. So far, HPLC (high performance liquid
chromatography) [12], spectrophotometry, GC-TMS (gas chromatography- tandem mass
spectrometry) [13, 14], fluorescence sensor [15], capillary zone electrophoresis and
electrochemical sensor [16] techniques were used to determine the amlodipine. However, the
results in considerable determination of amlodipine sensing in biological samples. Nevertheless,
2

it has drawbacks on the selectivity, over time consuming and expensive [17, 18]. Recently,
electrochemical techniques are provide relatively low cost, facile, easy to operate, good
sensitivity and excellent selectivity. Therefore, the fabrication of modified electrodes have been
focused more interest in the research and medical development field.
Recently, bimetal oxide is providing exciting new capabilities for research and
development in physical and chemical science [10, 19, 20]. In particular, transition series has
recently emerged as a promising area in various applications such as supercapacitor [21], photo-
degradation [22], batteries [23], hydrogen storage [24], electrochemical sensors [25], CO2 and
CO reduction [26]. NiMoO4 has attracted widespread interests due to the ever-increasing demand
for electrocatalytic materials. Here, NiMoO4 for electrochemical sensor due to their excellent
features, including intrinsic properties and electrical conductivity [27]. However, the practical
applications of NiMoO4 in electrochemical sensor are still hinder due to the moderate of sensing
ability and stability [28-33]. Hitherto, various electrode materials including conducting
biopolymer, carbonaceous materials, and transition metals have been used to develop superior
electrocatalytic performances [7, 33-36]. From the past decades, chitosan, a biopolymer has
attracted more interest in electrochemical, biocompatible and biodegradable properties [37, 38].
It has been well-established that biomedical applications and generally show higher
electrocatalytic activity than other biopolymer materials due its unique features including
excellent electrical conductivity, thermal stability, flexibility and large active surface area to
anchor and ability to fast electron transfer [17, 39-42]. Therefore, the choice has been made with
biopolymer to enhance the performance of nanomaterial in electrochemical sensor.
3

Scheme 1. Sonochemical synthesis of NiMoO4/CHIT nanocomposite
Herein, we present our research in developing low-cost, simple and environmental friendly
sonochemical-assisted method to prepare NiMoO4/CHIT for drug sensing. Our study describes
the strategies for improving the reproducibility and sensitivity voltammetry method to usability
of drug sensing by NiMoO4/CHIT modified glassy carbon electrode (Scheme 1 and 2). However,
literature reports on the application of NiMoO4/CHIT for electrochemical detection of drug are
rare. Herein, we report for a novel and sensitive sensor for the electrochemical detection of
amlodipine using NiMoO4/CHIT nanocomposite modified electrodes, which exhibit remarkable
sensitivities and desirable detection limits. In addition, the practicality and feasibility ability of
NiMoO4/CHIT modified glassy carbon electrode toward drug sensor in tablet and human serum
samples.
4

2. Experimental part
2.1. Sonochemical assisted synthesis of NiMoO4/CHIT
NiMoO4 nanosheets was synthesized by sonochemical technique [43]. The synthesis, 0.2 g
of ammonium molybdate ((NH4)6Mo7O24·4H2O) and 0.1 g of nickel(II) acetate tetrahydrate
(Ni(CH3COO)2·4H2O) were dissolved in 50 ml of deionized water (chemicals and methods are
given in supporting information). Then the above solution was heated at 75°C for 30 min under
stirring. Then the reaction temperature was increased to 90°C and then treated by ultrasonic
irradiation 60 W power and 20 kHz frequency (Misonix S-4000). Finally, the yellow-green
product was obtained by washed with deionized water and ethanol and dried. The NiMoO4/CHIT
was prepared by the chitosan biopolymer assisted sonochemical exfoliation of NiMoO4/CHIT.
First, the chitosan biopolymer was dissolved in the ethanol. The 10 mg of NiMoO4 nanoparticles
was added into 10 mL of chitosan and dispersed in deionized water and directly used for the
electrochemical applications.
2.2. Fabrication of NiMoO4/CHIT/GCE
Prior to modification, the glassy carbon electrode (0.071 cm2, Gaoss Union Co. Ltd.,
China) was polished with 0.05 µm alumina powder and then the electrode was sonicated in re-
distilled water for 5 min. After that, the dispersed NiMoO4/CHIT solution was (eight µL) drop
casting onto the clean surface of glassy carbon electrode. The drop casted glassy carbon
electrode was dried out at room temperature and the modified NiMoO4/CHIT/glassy carbon
electrode was used to the further all-electrochemical studies.
5

3. Results and discussions
3.1. XRD analysis
The XRD pattern of NiMoO4/CHIT showed several diffraction peaks, which are originate
from the (112), (220), (222), (200), (330), (204), (510), (150) and (530) phases of NiMoO4
nanosheets (figure 1). The phase of NiMoO4 is similar to its cubic phase structure with JCPDS
labeled number of 13-0128 [44, 45]. Hence, the formation of NiMoO4/CHIT was conformed in
the XRD analysis.
NiMoO4 sheets
JCPDS NO: 13-0128
2 theta (degree)
Figure 1. XRD analysis of NiMoO4/CHIT nanocomposite.
3.2. Structural and morphological studies
Next, the morphological aspect of the nanocomposite was studied by TEM (figure 2A). The
micrograph of NiMoO4 displays mostly nanosheets, while the TEM image of NiMoO4 is featured
with the characteristic sheet-like morphology (figure 2B). However, the SEM image of
NiMoO4/CHIT nanocomposite shows the presence of NiMoO4 nanosheets well distributed with
6

CHIT (figure 2C). A good electrostatic-attractive interaction between NiMoO4 sheets and CHIT
are possibly stabilizing them in the nanocomposite form. The EDX spectrum of NiMoO4/CHIT
revealed signals for the expected elements, such as carbon, nitrogen, oxygen, nickel and
molybdenum signals (figure S1). The elemental mapping of NiMoO4 nanosheets displayed the
homogeneous distribution of nickel (D), molybdenum (E) and oxygen (F) in the NiMoO4/CHIT
(figure 2D-F).
((CC))
(B)
(A)
NiMoO4
Ni
NiMoO4
NiMoO4
(F)
(D)
(E)
O
Ni
Mo
Figure 2. TEM images of NiMoO4 nanosheets (A-B) and SEM image of NiMoO4 (C). Elemental
mapping analysis of NiMoO4/CHIT (D-F).
3.3. Electrochemical analysis of amlodipine at NiMoO4@CHIT modified GCE
Under optimum condition, the electrochemical sensor performance of
NiMoO4/CHIT/GCE and unmodified GCE were analyzed by cyclic voltammetry (CV). The
cyclic voltammograms of unmodified GCE (b) and NiMoO4/CHIT/GCE (c) toward 100 µM
7

amlodipine in phosphate buffer (pH = 7.0) are shown in figure 3A. A feeble oxidation peak was
observed at potential of 0.83 V at unmodified GCE, indicates the electrode is incapability to
catalyze the oxidation reaction of amlodipine drug. The CV of NiMoO4/CHIT modified GCE
exhibited good oxidation peak at lower potential of 0.78 V with high intensity of current. On the
other hand, NiMoO4/CHIT/GCE shows a sharp peak compare to the bare GCE. Notably, the
result indicates that NiMoO4/CHIT/GCE has excellent electrocatalytic and sensing ability
towards oxidation of amlodipine drug. The electrochemical oxidation (ECO) of amine group to
pyridine position, the reaction is involving with -2e– and -2H+ process and the mechanism is
shown in Scheme 2. Moreover, its irreversible process based on the modified electrode surface.
After the electrochemical oxidation, the pyridine position is more stable. Therefore, the
reversible reduction process is not possible in pH 7.0. In figure 3A, it indicates that the
NiMoO4/CHIT/GCE has 2.8 folds larger than that at unmodified GCE. Moreover, the superior
electrochemical performance of NiMoO4/CHIT/GCE is due to the excellent synergic effect
between NiMoO4 and CHIT toward amlodipine sensing.
B
A
c
e
a
b
a
8

Figure 3. (A) CV responses of NiMoO4/CHIT (c) modified and unmodified (b) GCE in
phosphate buffer (0.05 M; pH 7.0) at 50 mV/s in the presence of 100 M amlodipine and the
absence of amlodipine (a) (n=3). (B) CVs of oxidation of amlodipine at NiMoO4/CHIT/GCE for
different concentration (25 to 125 M) and (inset) the calibration plot of anodic peak current vs.
[amlodipine]/M.
In figure 3B, shows the CVs of NiMoO4/CHIT/GCE towards different concentrations of
amlodipine drug. When the concentration of amlodipine drug increase, the peak current is also
increases linearly from 25 to 125 µM without any fouling. In figure 3B, inset shows the plot
between peak current and corresponding concentration of amlodipine drug, its exhibits good
linearity, thus the NiMoO4/CHIT nanocomposite modified electrode holds superior
electrochemical sensing ability towards drug sensing.
Cl
Cl
-2e-,-2H+
2H+,-2e-
O
O
C
O
O
C
-
C
C
Oxidation
O
O
O
O
O
O
NH2
NH2
N
N
H
Amlodipine
Scheme 2. Systematic mechanism of the electrocatalytic oxidation of amlodipine drug.
3.4. Effect of scan rate and various pHs
The influence of scan rate on NiMoO4/CHIT/GCE in 0.05 M phosphate buffer at a scan
rate of 50 mV/s containing 100 µM of amlodipine was examined by electrochemical studies,
9

figure 4A shows the CV results by means of increasing with the scan rate from 20 to 160 mV/s
and oxidation peak current density increases and anodic current potential has the ability to shift
towards higher positive value, such that the corresponding linear regression equation was
acquired to be Ipa = 51.103x + 13.452 (R² = 0.9909) with excellent linear relationship between
scan rate and oxidation peak currents shown in figure 4B. Therefore, these results indicate that
the oxidation of amlodipine drug based on NiMoO4/CHIT/GCE is diffusion-controlled process.
Moreover, the electrochemical peak potential was shifted to negative direction when the scan
rate was increased which can be attributed to the fast electron transfer process of totally
irreversible electrode reaction.
A
B
h
a
Figure 4. (A) CVs of oxidation of amlodipine at NiMoO4/CHIT/GCE for different scan rate (20
to 160 mV/s). (B) The calibration plot of anodic peak current vs. square root of the scan rate.
The pH value was optimized by measuring the CV responses of modified electrodes in
100 µM amlodipine at the scan rate of 50 mV/s. Different ranges of supporting electrolyte was
investigated. The phosphate buffer with maximum efficacy on the oxidation peak current
response was selected. The effect of 0.05 M phosphate buffer pH on the DPV determination of
10

amlodipine drug was studied in the range of 3.0 to 11.0. In figure 5A, shows that the pH
increasing pH from 3.0 to 11.0, the oxidation peaks potential shifts toward more negative value.
The pH 7.0 is high current responses according to figure 5A and B with correlation coefficient of
(R2) 0.9945. Due to pH 7.0 being the normal pH in human and animal biological fluids and the
sensitivity of this sensor, pH 7.0 was chosen for use as the supporting electrolyte in all
subsequent analytical experiments.
A
B
3
11
Figure 5. (A) CV responses of 100 µM of amlodipine in various pH ranging from 3.0 to 11.0 at
NiMoO4/CHIT/GCE (n=3) and (B) calibration plot for anodic peak current/µM vs. pH.
3.5. Electrocatalytic determination of amlodipine based on NiMoO4/CHIT/GCE by DPV
The analytical behavior of NiMoO4/CHIT/GCE to different additions of amlodipine was
investigated also by differential pulse voltammetry (DPV) experiments in 0.05 M phosphate
buffer at a scan rate of 50 mV/s (figure 6A). The DPV current response at NiMoO4/CHIT
modified GCE attained for different concentration of amlodipine drug from 0.025 to 373.6 µM in
0.05 M phosphate buffer at a scan rate of 50 mV/s. The DPV peak responses shown how it is
sensitive even at very low concentration (nanomolar). The calibration plot shows that the results
11

in figure 6B. According to the DPV results, the anodic current intensity is increases linearly
towards lower to higher concentration of amlodipine drug. It is evidently seen that the oxidation
peaks current of amlodipine increases (0.025 to 373.6 µM). In figure 6B shows a good linearity
between the anodic peak current and concentration of drug with a correlation coefficient (R2) of
0.9941 from the linear regression equation of Ipa = 0.3375x – 0.241. The limit of detection
(LOD) is expressed with 3*Sb/g (Sb is the standard deviation of blank sample and g is the slop of
the calibration curve). The LOD was obtained 4.62 nM. Furthermore, the sensitivity was
evaluated to be 4.753 µA.µM-1.cm-2. The electrochemical sensor performance of NiMoO4/CHIT
modified GCE was compared with previously reported sensor and results are given in Table 1.
The limit of quantification (LOQ) of the enhanced sensor was calculated (24.65 nM) using the
equation, LOQ=3*Sb/g. It can be seen that our NiMoO4/CHIT proposed sensor in this work
shows improved electrochemical performance of the sensor compared to some of those recently
reported electrochemical amlodipine sensors. Compared with conventional electrodes, our
modified sensors present several advantages as they are highly versatile, cost-effective, user-
friendly, and can be use in on-site detection.
B
A
373.6 µM
25 nM
12

Figure 6. (A) DPV responses of NiMoO4/CHIT/GCE in phosphate buffer with different
concentration of amlodipine. (B) Calibration plot of peak current/µA vs. [amlodipine]/µM.
Table 1. Comparison between the sensor performance of NiMoO4/CHIT modified GCE with
other previously reported towards amlodipine sensor.
Electrodes
Linear range
Limit of detection References
MWCNT/GCE
0.017–0.52 μM
0.009 μM
[46]
Carbon nanotubes/GCE
MWCNT/gold electrode
boron-doped diamond electrode
EPPGE
4.3–170 μM
24–34 μM
1.7 μM
4.2 μM
[47]
[48]
6–38 μM
0.07 μM
0.001 μM
0.12 μM
0.08 μM
7.9 μM
[49]
0.005–1 μM
8.1–41 μM
[50]
GCE
[51]
Fe3O4@SiO2/MWCNT/GCE
Nickel hydroxide/GCE
NiMoO4/CHIT/GCE
0.25–500 μM
13.9–167 μM
0.1 to 374.5 µM
[52]
[4]
12.74 nM
This work
3.6. Selectivity analysis of amlodipine sensor based on NiMoO4/CHIT/GCE
To investigate the selectivity of the proposed method, an important parameter for the
newly developed electrochemical sensor and the effect of some interfering analyte on the
determination of drug was evaluated by DPV method. Selectivity of the NiMoO4/CHIT modified
13

electrode to detect amlodipine (ALP) in presence of potential possible interferents such as,
dopamine (DA), ascorbic acid (AA), folic acid (FA), uric acid (UA), glucose (Glu), K+, Na+,
Fe2+ and H2O2 has been studied via DPV method. In figure 7A displays the calibration plot of
NiMoO4/CHIT modified electrode toward 100 μM of amlodipine and 0.5 mM of aforementioned
interfering species. As shown in figure 7A, the electrode quickly responded to the low
concentration amounts of amlodipine, while it was not responding to other species even at high
concentrations, suggests excellent selectivity of the electrode. The corresponding histogram is
also reflect the same observation in a more clear way (Figure 7A). Moreover, figure 7A shows
the modified electrode was tested in presence of metal ions (K+, Na+ and Fe2+; 1 mM) and
amlodipine concentration was varied in presence of metal ions. The results show that the
NiMoO4/CHIT modified electrode has good selective in presence of metal ions and biological
analytes.
B
A
Figure 7. (A) DPVs recorded for amlodipine oxidation in the presence of different interfering
compounds (DA-dopamine, AA-ascorbic acid, FA-folic acid, UA-uric acid, Glu-glucose, K+,
14

Na+, Fe2+ and H2O2) at NiMoO4/CHIT/GCE. (B) Stability analysis of NiMoO4/CHIT/GCE
(n=3).
3.7. Reproducibility, repeatability and stability analysis of NiMoO4/CHIT/GCE
The stability of NiMoO4/CHIT/GCE was also examined. The DPV experiments were also
carried out using the modified electrode once a day under the same operation conditions. In order
to ascertain the stability of the proposed electrochemical sensor, the anodic peak current intensity
was investigated by DPV for over a period of 20 days at NiMoO4/CHIT/GCE (figure 7B). The
sensor can be kept at room temperature. After 20 days of storage, the obtained peak current
response for the modified electrode decreases only by 4.57% from its initial current response.
Therefore, the NiMoO4/CHIT modified sensor retains superior stability as well as excellent
applicable electrode material towards the electrochemical oxidation of amlodipine drug.
The reproducibility experiment was analyzed by DPV for four independent
NiMoO4/CHIT modified GCE in 0.05 M phosphate buffer containing 100 µM of amlodipine
drug and its consistent result is shown in figure 8A along with the current response for the
oxidation of amlodipine drug is represented as calibration diagram is displayed. The obtained
results clearly explained that the developed sensor exhibits outstanding reproducibility with
relative standard deviation (RSD) of 3.15%. Besides that, the repeatability test was investigated
for identical NiMoO4/CHIT nanocomposite modified electrode containing 100 µM of
amlodipine drug concentration in PB (pH 7.0) at a scan rate of 50 mV/s, we observed nearly
equivalent current response (figure 8B) with less deviation of less than 3.6% for repeated fifteen
runs at single NiMoO4/CHIT modified GCE with RSD of 3.28%. From these studies, it
successfully reveals that the good electrochemical sensor possesses predominant performance
towards the detection of amlodipine drug.
15

B
A
Figure 8. (A) Reproducibility analysis of NiMoO4/CHIT/GCEs (n=3) and (B) repeatability
analysis of NiMoO4@CHIT/GCE.
3.8. Real sample analysis
Practical applicability of the modified electrode was demonstrated in pharmaceutical
product and biological samples. Amlodipine tablet samples were collected from a pharmaceutical
company and diluted in phosphate buffer pH 7.0. Then, the resulting samples are analyzed by
DPV and then known amounts of amlodipine were spiked to prepare stock real sample solution.
Afterwards, aliquots (each 5, 25 and 50 μM) of lab sample and spiked drug samples were
injected into the supporting electrolyte. The electrode delivered prompt and stable sensor
responses toward each addition of real samples. The amount of amlodipine added, found and
recovery are calculated and given in Table 2. They are in the agreeable analytical range,
indicating the suitably of the method in analyzing amlodipine in drug samples. The same sets of
experiments were carried out using human serum samples in parallel, and the obtained results are
given in Table 2. The biological samples were collected from Chang Gung Memorial Hospital.
16

Table 2. Determination of amlodipine in real sample analysis in biological and pharmaceutical
samples
Samples
Added (µM)
Found (µM)
Recovery (%)
RSD (%)
(n=3)
3.16
Urine
5
4.76
23.61
47.11
4.68
95.2
94.44
94.22
93.6
25
50
5
2.68
3.49
amlodipine
tablet
3.28
25
50
24.19
48.37
96.76
96.74
3.62
2.94
4. Conclusion
In this research, we have synthesized more potential nanosheets like nickel molybdate by
simple sonochemical method. A simple, novel and low-cost electrochemical sensor for the rapid
determination of amlodipine using NiMoO4/CHIT nanocomposite was developed. The
morphological and surface properties of as-synthesized NiMoO4/CHIT nanocomposite samples
were characterized by XRD pattern, SEM, TEM, EDX and mapping analysis. Furthermore, the
NiMoO4/CHIT/GCE was scrutinized for the electrochemical sensing of amlodipine.
Fascinatingly, the developed sensor retains higher electrocatalytic activity with low LOD, LOQ,
wide linear range, excellent selectivity, reproducibility and repeatability. Upon considering the
above-obtained results, the as-synthesized nanocomposite could be utilized for futurity
electrochemical applications including biosensor and practical pharmaceutical analysis.
17

Acknowledgement
The authors gratefully acknowledge the financial support of the Ministry of Science and
Technology, Taiwan through contract nos. MOST108-2221-E-182-030 and MOST 107-2113-M-
027-005-MY3. The financial support from the Chang Gung Memorial Hospital through contract
no. CMRPD5H0032 to B.S. Lou is also acknowledged.
Conflict of interest
The authors declare that they have no conflicts of interest to this research work.
Reference
[1]
N.F. Atta, A. Galal, Y.M. Ahmed, H. Ekram, Design strategy and preparation of a
conductive layered electrochemical sensor for simultaneous determination of ascorbic
acid, dobutamine, acetaminophen and amlodipine, Sensors and Actuators B: Chemical,
(2019) 126648.
[2]
[3]
E. Djaalab, M. Samar, S. Zougar, R. Kherrat, Electrochemical Biosensor for the
Determination of Amlodipine Besylate Based on Gelatin–Polyaniline Iron Oxide
Biocomposite Film, Catalysts, 8 (2018) 233.
M. Govindasamy, V. Mani, S.-M. Chen, T. Maiyalagan, S. Selvaraj, T.-W. Chen, S.-Y.
Lee, W.-H. Chang, Highly sensitive determination of non-steroidal anti-inflammatory
drug nimesulide using electrochemically reduced graphene oxide nanoribbons, RSC
Advances, 7 (2017) 33043-33051.
18

[4]
[5]
[6]
W.B. Machini, D.N. David-Parra, M.F. Teixeira, Electrochemical investigation of the
voltammetric determination of hydrochlorothiazide using a nickel hydroxide modified
nickel electrode, Materials Science and Engineering: C, 57 (2015) 344-348.
H. Hrichi, L. Monser, N. Adhoum, A novel electrochemical sensor based on
electropolymerized molecularly imprinted poly (aniline-co-anthranilic acid) for sensitive
detection of amlodipine, Journal of Electroanalytical Chemistry, 805 (2017) 133-145.
M. Govindasamy, S.-M. Chen, V. Mani, R. Devasenathipathy, R. Umamaheswari, K.J.
Santhanaraj, A. Sathiyan, Molybdenum disulfide nanosheets coated multiwalled carbon
nanotubes composite for highly sensitive determination of chloramphenicol in food
samples milk, honey and powdered milk, Journal of colloid and interface science, 485
(2017) 129-136.
[7]
M. Govindasamy, S.-F. Wang, B. Subramanian, R.J. Ramalingam, H. Al-lohedan, A.
Sathiyan, A novel electrochemical sensor for determination of DNA damage biomarker
(8-hydroxy-2’-deoxyguanosine) in urine using sonochemically derived graphene oxide
sheets covered zinc oxide flower modified electrode, Ultrasonics Sonochemistry, (2019)
104622.
[8]
[9]
L. Zhang, P. Song, H. Long, M. Meng, Y. Yin, R. Xi, Magnetism based electrochemical
immunosensor for chiral separation of amlodipine, Sensors and Actuators B: Chemical,
248 (2017) 682-689.
M. Arvand, H.A. Samie, Electrospun CeO 2–Au nanofibers/graphene oxide 3D
nanonetwork structure for the electrocatalytic detection of amlodipine, Ionics, 24 (2018)
1813-1826.
19

[10] U. Rajaji, M. Govindasamy, S.-M. Chen, T.-W. Chen, X. Liu, S. Chinnapaiyan,
Microwave-assisted synthesis of Bi2WO6 flowers decorated graphene nanoribbon
composite for electrocatalytic sensing of hazardous dihydroxybenzene isomers,
Composites Part B: Engineering, 152 (2018) 220-230.
[11] U. Rajaji, K. Murugan, S.-M. Chen, M. Govindasamy, T.-W. Chen, P.H. Lin, Graphene
oxide encapsulated 3D porous chalcopyrite (CuFeS2) nanocomposite as an emerging
electrocatalyst for agro-hazardous (methyl paraoxon) detection in vegetables, Composites
Part B: Engineering, 160 (2019) 268-276.
[12] K. Pandya, M. Satia, T. Gandhi, I. Modi, R. Modi, B. Chakravarthy, Detection and
determination of total amlodipine by high-performance thin-layer chromatography: a
useful technique for pharmacokinetic studies, Journal of Chromatography B: Biomedical
Sciences and Applications, 667 (1995) 315-320.
[13] S. Tatar, S. Atmaca, Determination of amlodipine in human plasma by high-performance
liquid chromatography with fluorescence detection, Journal of Chromatography B:
Biomedical Sciences and Applications, 758 (2001) 305-310.
[14] B. Streel, C. Laine, C. Zimmer, R. Sibenaler, A. Ceccato, Enantiomeric determination of
amlodipine in human plasma by liquid chromatography coupled to tandem mass
spectrometry, Journal of biochemical and biophysical methods, 54 (2002) 357-368.
[15] B.A. Moussa, A.A. El-Zaher, M.A. Mahrouse, M.S. Ahmed, Simultaneous determination
of amlodipine besylate and atorvastatin calcium in binary mixture by spectrofluorimetry
and HPLC coupled with fluorescence detection, Analytical chemistry insights, 8 (2013)
ACI. S12921.
20

[16] S. Yaqoob, S. Rahim, A.M. Bhayo, M.R. Shah, A. Hameed, M.I. Malik, A Novel and
Efficient Colorimetric Assay for Quantitative Determination of Amlodipine in
Environmental, Biological and Pharmaceutical Samples, ChemistrySelect, 4 (2019)
10046-10053.
[17] V. Mani, M. Govindasamy, S.-M. Chen, T.-W. Chen, A.S. Kumar, S.-T. Huang, Core-
shell heterostructured multiwalled carbon nanotubes@ reduced graphene oxide
nanoribbons/chitosan, a robust nanobiocomposite for enzymatic biosensing of hydrogen
peroxide and nitrite, Scientific reports, 7 (2017) 11910.
[18] V. Mani, M. Govindasamy, S.-M. Chen, R. Karthik, S.-T. Huang, Determination of
dopamine using a glassy carbon electrode modified with a graphene and carbon nanotube
hybrid decorated with molybdenum disulfide flowers, Microchimica Acta, 183 (2016)
2267-2275.
[19] S.-M. Chen, R. Umamaheswari, G. Mani, T.-W. Chen, M.A. Ali, A.-H. Fahad, M.
Elshikh, M.A. Farah, Hierarchically structured CuFe 2 O 4 ND@ RGO composite for the
detection of oxidative stress biomarker in biological fluids, Inorganic Chemistry
Frontiers, 5 (2018) 944-950.
[20] T.-W. Chen, U. Rajaji, S.-M. Chen, M. Govindasamy, S.S.P. Selvin, S. Manavalan, R.
Arumugam, Sonochemical synthesis of graphene oxide sheets supported Cu2S nanodots
for high sensitive electrochemical determination of caffeic acid in red wine and soft
drinks, Composites Part B: Engineering, 158 (2019) 419-427.
[21] M. Govindasamy, S. Shanthi, E. Elaiyappillai, S.-F. Wang, P.M. Johnson, H. Ikeda, Y.
Hayakawa, S. Ponnusamy, C. Muthamizhchelvan, Fabrication of hierarchical NiCo2S4@
CoS2 nanostructures on highly conductive flexible carbon cloth substrate as a hybrid
21

electrode material for supercapacitors with enhanced electrochemical performance,
Electrochimica Acta, 293 (2019) 328-337.
[22] S.K. Ray, D. Dhakal, S.W. Lee, Rapid degradation of naproxen by AgBr-α-NiMoO4
composite photocatalyst in visible light: mechanism and pathways, Chemical Engineering
Journal, 347 (2018) 836-848.
[23] J.-S. Park, J.S. Cho, Y.C. Kang, Scalable synthesis of NiMoO4 microspheres with
numerous empty nanovoids as an advanced anode material for Li-ion batteries, Journal of
Power Sources, 379 (2018) 278-287.
[24] T. Dong, M. Li, P. Wang, P. Yang, Synthesis of hierarchical tube-like yolk-shell
Co3O4@ NiMoO4 for enhanced supercapacitor performance, International Journal of
Hydrogen Energy, 43 (2018) 14569-14577.
[25] K. Xu, Q. Tang, W. Zhao, X. Yu, Y. Yang, T. Yu, C. Yuan, In situ growth of Co3O4@
NiMoO4 composite arrays on alumina substrate with improved triethylamine sensing
performance, Sensors and Actuators B: Chemical, (2019) 127154.
[26] X. Du, J. Fu, X. Zhang, NiCo2O4@ NiMoO4 Supported on Nickel Foam for
Electrocatalytic Water Splitting, ChemCatChem, 10 (2018) 5533-5540.
[27] S. Chen, Z. Zhang, W. Zeng, J. Chen, L. Deng, Construction of NiCo2S4@ NiMoO4
Core‐Shell Nanosheet Arrays with Superior Electrochemical Performance for
Asymmetric Supercapacitors, ChemElectroChem, 6 (2019) 590-597.
[28] X. Guo, H. Dong, T. Xia, T. Wang, H. Jia, L. Zhu, Highly Efficient Degradation toward
Tylosin in the Aqueous Solution by Carbon Spheres/g-C3N4 Composites under
Simulated Sunlight Irradiation, ACS Sustainable Chemistry & Engineering, 6 (2018)
12776-12786.
22

[29] Q. Bkour, O.G. Marin-Flores, M.G. Norton, S. Ha, A highly active and stable bimetallic
Ni-Mo2C catalyst for a partial oxidation of jet fuel, Applied Catalysis B: Environmental,
245 (2019) 613-622.
[30] M. Govindasamy, V. Mani, S.-M. Chen, T.-W. Chen, A.K. Sundramoorthy, Methyl
parathion detection in vegetables and fruits using silver@ graphene nanoribbons
nanocomposite modified screen printed electrode, Scientific reports, 7 (2017) 46471.
[31] M. Govindasamy, B. Subramanian, S.-F. Wang, S. Chinnapaiyan, R.J. Ramalingam, H.
Al-lohedan, Ultrasound-Assisted Synthesis of Tungsten Trioxide Entrapped with
Graphene Nanosheets for Developing Nanomolar Electrochemical (Hormone) Sensor and
Enhanced Sensitivity of the Catalytic Performance, Ultrasonics Sonochemistry, (2019).
[32] M. Govindasamy, S.-F. Wang, R. Jothiramalingam, S.N. Ibrahim, H.A. Al-lohedan, A
screen-printed electrode modified with tungsten disulfide nanosheets for nanomolar
detection of the arsenic drug roxarsone, Microchimica Acta, 186 (2019) 420.
[33] M. Govindasamy, S.-F. Wang, S. Kumaravel, R.J. Ramalingam, H.A. Al-lohedan, Facile
synthesis of copper sulfide decorated reduced graphene oxide nanocomposite for high
sensitive detection of toxic antibiotic in milk, Ultrasonics sonochemistry, 52 (2019) 382-
390.
[34] F. Xiao, F. Zhao, Y. Zhang, G. Guo, B. Zeng, Ultrasonic electrodeposition of gold−
platinum alloy nanoparticles on ionic liquid− chitosan composite film and their
application in fabricating nonenzyme hydrogen peroxide sensors, The Journal of Physical
Chemistry C, 113 (2008) 849-855.
23

[35] A. Bouvree, J.-F. Feller, M. Castro, Y. Grohens, M. Rinaudo, Conductive polymer nano-
biocomposites (CPC): chitosan-carbon nanoparticle a good candidate to design polar
vapour sensors, Sensors and Actuators B: Chemical, 138 (2009) 138-147.
[36] M. Govindasamy, S.-F. Wang, W.C. Pan, B. Subramanian, R.J. Ramalingam, H. Al-
lohedan, Facile sonochemical synthesis of perovskite-type SrTiO3 nanocubes with
reduced graphene oxide nanocatalyst for an enhanced electrochemical detection of α-
amino acid (tryptophan), Ultrasonics sonochemistry, 56 (2019) 193-199.
[37] M. Potara, A.-M. Gabudean, S. Astilean, Solution-phase, dual LSPR-SERS plasmonic
sensors of high sensitivity and stability based on chitosan-coated anisotropic silver
nanoparticles, Journal of Materials Chemistry, 21 (2011) 3625-3633.
[38] S. Voznesenskiy, A. Sergeev, A.Y. Mironenko, S.Y. Bratskaya, Y.N. Kulchin,
Integrated-optical sensors based on chitosan waveguide films for relative humidity
measurements, Sensors and Actuators B: Chemical, 188 (2013) 482-487.
[39] M. Mathew, S. Sureshkumar, N. Sandhyarani, Synthesis and characterization of gold–
chitosan nanocomposite and application of resultant nanocomposite in sensors, Colloids
and Surfaces B: Biointerfaces, 93 (2012) 143-147.
[40] X.-L. Luo, J.-J. Xu, J.-L. Wang, H.-Y. Chen, Electrochemically deposited nanocomposite
of chitosan and carbon nanotubes for biosensor application, Chemical Communications,
(2005) 2169-2171.
[41] V. Mani, M. Govindasamy, S.-M. Chen, B. Subramani, A. Sathiyan, J.P. Merlin,
Determination of folic acid using graphene/molybdenum disulfide nanosheets/gold
nanoparticles ternary composite, Int. J. Electrochem. Sci., 12 (2017) e267.
24

[42] V. Mani, S. Shanthi, T.-K. Peng, H.-Y. Lin, H. Ikeda, Y. Hayakawa, S. Ponnusamy, C.
Muthamizhchelvan, S.-T. Huang, Real-time quantification of hydrogen peroxide
production in living cells using NiCo2S4@ CoS2 heterostructure, Sensors and Actuators
B: Chemical, 287 (2019) 124-130.
[43] G. Kianpour, M. Salavati-Niasari, H. Emadi, Sonochemical synthesis and
characterization of NiMoO4 nanorods, Ultrasonics sonochemistry, 20 (2013) 418-424.
[44] Q. Zhang, Y. Deng, Z. Hu, Y. Liu, M. Yao, P. Liu, Seaurchin-like hierarchical NiCo 2 O
4@ NiMoO 4 core–shell nanomaterials for high performance supercapacitors, Physical
Chemistry Chemical Physics, 16 (2014) 23451-23460.
[45] Y. Chen, B. Liu, Q. Liu, J. Wang, J. Liu, H. Zhang, S. Hu, X. Jing, Flexible all-solid-state
asymmetric supercapacitor assembled using coaxial NiMoO4 nanowire arrays with
chemically integrated conductive coating, Electrochimica Acta, 178 (2015) 429-438.
[46] A.R.M. Sikkander, C. Vedhi, P. Manisankar, Electrochemical determination of calcium
channel blocker drugs using multiwall carbon nanotube-modified glassy carbon electrode,
International Journal of Industrial Chemistry, 3 (2012) 29.
[47] A. Mohammadi, A.B. Moghaddam, K. Eilkhanizadeh, E. Alikhani, S. Mozaffari, T.
Yavari, Electro-oxidation and simultaneous determination of amlodipine and atorvastatin
in commercial tablets using carbon nanotube modified electrode, Micro & Nano Letters,
8 (2013) 413-417.
[48] Z. Stoiljković, M. Avramov Ivić, S.D. Petrović, D. Mijin, S. Stevanović, U. Lačnjevac,
A. Marinković, Voltammetric and square-wave anodic stripping determination of
amlodipine besylate on gold electrode, Int. J. Electrochem. Sci, 7 (2012) 2288-2303.
25

[49] L.u. Švorc, K. Cinková, J. Sochr, M. Vojs, P. Michniak, M. Marton, Sensitive
electrochemical determination of amlodipine in pharmaceutical tablets and human urine
using a boron-doped diamond electrode, Journal of Electroanalytical Chemistry, 728
(2014) 86-93.
[50] R.N. Goyal, S. Bishnoi, Voltammetric determination of amlodipine besylate in human
urine and pharmaceuticals, Bioelectrochemistry, 79 (2010) 234-240.
[51] G. Altiokka, D. Dogrukol‐Ak, M. Tunçel, H.Y. Aboul‐Enein, Determination of
Amlodipine in Pharmaceutical Formulations by Differential‐Pulse Voltammetry with a
Glassy Carbon Electrode, Archiv der Pharmazie: An International Journal Pharmaceutical
and Medicinal Chemistry, 335 (2002) 104-108.
[52] H. Beitollahi, F. Ebadinejad, F. Shojaie, M. Torkzadeh-Mahani, A magnetic core–shell
Fe 3 O 4@ SiO 2/MWCNT nanocomposite modified carbon paste electrode for amplified
electrochemical sensing of amlodipine and hydrochlorothiazide, Analytical Methods, 8
(2016) 6185-6193.
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Research highlights
 A facile and green sonochemical synthesis of NiMoO4/CHIT nanocomposite
 The nanocomposite was characterized by SEM, TEM, EDX, XRD and CV
 The obtained NiMoO4/CHIT NC applied to the electrochemical detection of calcium
channel blocker drug (amlodipine)
 The modified sensor has explored high sensitivity and nanomolar detection limit towards
amlodipine drug
27