Accepted Manuscript

Epinehrine electrochemical sensor based on a carbon paste electrode modified

with hydroquinone derivative and graphene oxide nano-sheets: Simultaneous
determination of epinephrine, acetaminophen and dopamine

Marzieh Dehghan Tezerjani, Ali Benvidi, Afsaneh Dehghani Firouzabadi,

Mohammad Mazloum-Ardakani, Ali Akbari

PII: S0263-2241(17)30039-8
DOI: http://dx.doi.org/10.1016/j.measurement.2017.01.029
Reference: MEASUR 4552

To appear in: Measurement

Received Date: 12 February 2016

Revised Date: 9 January 2017
Accepted Date: 17 January 2017

Please cite this article as: M.D. Tezerjani, A. Benvidi, A.D. Firouzabadi, M. Mazloum-Ardakani, A. Akbari,
Epinehrine electrochemical sensor based on a carbon paste electrode modified with hydroquinone derivative and
graphene oxide nano-sheets: Simultaneous determination of epinephrine, acetaminophen and dopamine,
Measurement (2017), doi: http://dx.doi.org/10.1016/j.measurement.2017.01.029

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 Epinehrine electrochemical sensor based on a carbon paste electrode modified with

hydroquinone derivative and graphene oxide nano-sheets: Simultaneous determination of

epinephrine, acetaminophen and dopamine

Marzieh Dehghan Tezerjani, Ali Benvidi1, Afsaneh Dehghani Firouzabadi, Mohammad

Mazloum-Ardakani, Ali Akbari

Department of Chemistry, Faculty of Science, Yazd University, Yazd, 89195-741, Iran

Department of Chemistry, Faculty of Science, Jiroft University, kerman, 89195-741, Iran

Abstract

In this paper, an electrochemical sensor was constructed for determination of epinephrine

based on carbon paste electrode (CPE) modified with graphene oxide (GO) and 2-(5-Ethyl-2,4-

dihydroxyphenyl)-5,7-dimethyl-4H-pyrido[2,3-d][1,3]thiazine-4-one (EDDPT) as modifiers. The

modified electrode was applied as an electrochemical sensor for oxidation of epinephrine (EP).

Under the optimum conditions, the over potential of EP oxidation decreased about 279 mV at the

modified CPE more than a non-modified CPE. Electrochemical behavior of EP was investigated

on the fabricated electrode by cyclic voltammetry (CV) and differential pulse voltammetry

(DPV) methods, and some kinetic parameters of EP were obtained, too. The linear range and the

detection limit for EP were found to be 1.5–600.0 μM and 0.65 µM (based on 3s/m), respectively

using the EDDPT/GO/CPE sensor and the differential pulse voltammetry (DPV) method. Also,

the designed electrochemical sensor was applied to determine EP in the drug sample and

1
Corresponding author Tel.: +98 353 812 2645; Fax: +98-353-8210644
e-mail addresses: abenvidi@yazd.ac.ir; benvidi89@gmail.com

1
simultaneous determination of epinephrine (EP), acetaminophen (AC) and dopamine (DA) in

human serum solutions.

Keywords: Modified electrode; Electrochemical sensor; electrocatalytic oxidation;

Epinephrine; Graphene oxide; Acetaminophen; Dopamine;

Introduction

Recently, new methods for measuring the various drugs have been introduced such as

spectroscopic and electrochemical methods [1]. Characteristics such as higher selectivity, better

sensitivity, higher speed, repeatability, cost and time made electrochemical methods more

suitable for measurement of some drugs [2]. The electrochemical sensors based on modified

electrodes have been improved due to some advantages such as being inexpensive, reproducible,

simple analytical method with high detection sensitivity, and ease of miniaturization [3-4].

Carbon paste electrode (CPE) is widely used in electrochemical analysis due to some advantages

such as possessing low cost, easy manufacturing, ease of use, low back ground current, wide

potential window, high sensitivity and easy modification [5-7]. Epinephrine (EP) and dopamine

(DA) are the best known catechol amines, which constitute a group of compounds with an alkyl

amine chain attached to a benzene ring with two hydroxyl groups [8]. Epinephrine (EP) as a

neurotransmitter is synthesized biologically in the adrenal medulla and sympathetic nerve

terminals. It has a key role in the functioning of central nervous system (CNS), renal, hormonal,

and cardiovascular system [9]. The existence of abnormal levels of EP causes several diseases

such as phaeochromocytoma, hypoglycaemia and myocardial infarction [10]. Several methods

have been reported for EP analysis [11-13] and due to electro active nature of EP, it can also be

determined electrochemically [14-16].

2
 Also, dopamine (DA) as a catecholamine neurotransmitter plays a key role in the central

nervous and hormones in the mammalian system [17]. If the value of DA is lower than normal it

may cause some neurological disorders such as Schizophrenia, Huntington’s disease, and

Parkinson’s diseases [18]. Other investigated material in this research was acetaminophen (N-

acetyl-p-aminophenol (AC)). It has been used comprehensively as a pharmaceutical pain reliever

for patients who are susceptible to aspirin [19]. Therefore a suitable selective, simple,

inexpensive, fast, sensitive and accurate detection method is required for determining EP,

especially in the presence of DA and AC.

Recently, various techniques have been developed for bio-components determination such as

enzyme based biosensors [20]. According to the existence of some bio components and drug in

the human bodies, some methods have been reported for determination of EP, DA and AC based

on the chemical modification of traditional electrode materials [21-22].

Recently, carbon-based nanostructures such as carbon nanofibers, carbon nanotubes (CNTs),

and mesoporous carbons have been noticeably used in the construction of modified electrodes.

These modified electrodes can be applied in both analytical and industrial electrochemistry, due

to their low price, suitable electrocatalytic activity for different redox reactions, possessing a

broad potential window, and relatively inert electrochemistry [23-27].

As known, graphene nano sheets, has a single layer of carbon atoms in a honeycomb two-

dimensional lattice [28]. The structure of graphene can lead to specific properties such as

suitable mechanical strength, large surface area, high conductivity and electron mobility at room

temperature. The modified electrodes with graphene have paid more attention due to high

electron conductivity and good biocompatibility [29]. Graphene oxide (GO) holds favorable

features of electronics and ᴨ-ᴨ stacking interaction [30]. Other properties of GO are facile

3
synthesis, high water dispensability, tunable surface functionalization, and good biocompatibility

[31]. It has various applications such as transparent conductors [32], sensors [33], super

capacitors [34], batteries, hydrogen storage [35] and nanocomposite materials [36]. In addition,

the electrochemical sensors based on modified electrodes with nanomaterials are applied for the

detection and determination of bio components such as EP and DA [37]. So, in the preset

research GO nano sheets were used due to the mentioned benefits for electrode modification

together with 2-(5-Ethyl-2,4-dihydroxyphenyl)-5,7-dimethyl-4H-pyrido[2,3-d] [1,3] thiazine-4-

one (EDDPT).

As mentioned in the present study a novel electrode was fabricated using a modified carbon

paste electrode (CPE) with graphene oxide (GO) and EDDPT. The combination of graphene

oxide (GO) and EDDPT in the fabrication of EDDPT/GO/CPE for detection of EP was used.

Due to the unique properties of GO [38] and using EDDPT, an increase in the peak current and a

decrease in the overpotential of EP were observed at the designed electrode compared to the bare

CPE. Under optimum conditions, some parameters of epinephrine such as the electron transfer

coefficient (α), the electron transfer rate constant )ks), the diffusion coefficient of species in a 0.1

M alkaline solution (pH=7) were obtained. The obtained results revealed that the proposed

sensor offers several advantages such as high sensitivity, repeatability and good stability. The

applicability of the modified electrode was successfully tested by voltammetric determination of

EP individually and simultaneous determination of EP, AC and DA.

2. Experimental method and materials

2.1. Instruments and chemicals

The electrochemical experiments were carried out using a potentiostat/galvanostat Autolab

model PGSTAT 30 (Eco Chemic, Utrecht, Netherlands) and a NOVA 1.7 software at laboratory

4
temperature (25±1°C). The working, counter and reference electrodes were, an

EDDPT/GO/CPE, a platinum electrode and an Ag/AgCl (sat.), KCl (3M) electrode, respectively.

Graphite powder (particle diameter: 0.10 mm) from Merck was used as the working electrode

(WE) substrate. For pH measuring a Metrohm model 691 pH/mV meter was used. Epinephrine,

dopamine, acetaminophen and another applied reagents were used with analytical grade (Merck,

Darmstadt, Germany). Phosphate buffer solutions (0.1 M) were prepared from 0.1 M H 3PO4-

NaH2PO4, and for pH regulating 0.1 M H3PO4 or NaOH was used.

2.2. The synthesis procedure of 2-(5-Ethyl-2,4-dihydroxyphenyl)-5,7-dimethyl-4H-

pyrido[2,3-d] [1,3] thiazine-4-one (EDDPT) modifier

(2-(5-Ethyl-2,4-dihydroxyphenyl)-5,7-dimethyl-4H-pyrido[2,3-d] [1,3] thiazine-4-one

(EDDPT)) as a modifier was synthesized by authors using the reported procedure [39]. Briefly,

the synthesis of EDDPT is explained as follows: a mixture of 0.248 g 2-amino-4, 6-

dimethylnicotinamide (Sigma-Aldrich, 1.5 mmol) and 0.616 g sulfinylbis [(5-ethyl-2,4-

dihydroxyphenyl) methanethione] (1.5 mmol) in 10 cm3 MeOH was heated to reflux for 3 h. The

hot mixture was filtered. The filtrate was concentrated and the formed solid was crystallized

from 4 cm3 MeOH to give 0.34 g (68 %) orange crystals of product. The obtained results for

characterization of modifier by 1H NMR, 13C NMR and IR are listed as follow:

1
H NMR (500 MHz, DMSO-d6): δ = 14.27 (s, 1H), 10.29 (s, 1H), 8.06 (s, 1H), 7.89 (s, 1H), 6.45
13
(s, 1H), 2.53 (q, J = 7.48 Hz, 2H), 2.39 (s, 3H), 2.31 (s, 3H), 1.13 (t, J = 7.48 Hz, 3H) ppm; C

NMR (125 MHz, DMSO-d6): δ = 168.8, 153.3, 152.2, 147.8, 136.2, 136.0, 128.1, 128.7, 123.1,

123.2, 119.7, 111.2, 102.2, 22.0, 21.0, 19.0, 14.1 ppm; IR (ATR): 3299, 3131, 2967, 1650, 1600,

1556, 1491, 1430, 1390, 1349, 1278, 1249, 1217, 1140, 1032, 900, 874, 732, 680 cm-1.

5
 CH3 O

S CH3

H3 C N N

HO OH

Fig. 1. The structure of 2-(5-Ethyl-2, 4-dihydroxyphenyl)-5,7-dimethyl-4H-pyrido[2,3-d] [1,3]

thiazine-4-one (EDDPT) as a modifier

2.3. The synthesis process of graphene oxide

The graphene nano sheets were synthesized according to the procedure offered in the

literature [40]. Briefly, a mixture of graphite/KMnO4 (3:18 g) and a mixture of H2SO4/H3PO4

(360:40 mL) were prepared at 50 °C. These two mixtures were added by shaking and then

stirring for 12 h. Then, the reaction product cooled down to 25 °C and was transferred into ice

bath containing 6 mL 30% H2O2. The obtained solution was centrifuged and then filtered, and

the obtained precipitate was washed with water, 30% HCl, and finally washed twice with 200

mL of ethanol. After sonication for 3 h, a colloidal suspension of graphene oxide nano sheets

were obtained in purified water (150 mg/50 mL). Also, the prepared GO was characterized with

FT-IR and UV/Vis spectroscopy methods.

2.4. Preparation of EDDPT/GO/CPE sensor

To prepare this electrochemical sensor, at first the ratios of EDDPT, GO and CPE were

optimized. Carbon paste was prepared by hand mixing of graphite powder (0.48 g), EDDPT

(0.005 g), GO (0.015 g) and Paraffin (Dc 350, Merck) using a mortar and pestle, and then was

inserted in the bottom of a glass tube (internal radius: 2 mm and 10 cm long). Electrical contact

was performed by pushing a piece of copper wire down the glass tube. When necessary, a fresh

6
surface of electrode was obtained by pushing an excess of the paste out of the tube and polishing

with a weighing paper. The designed sensor was used for determination of EP individually and

determination of EP, AC and DA simultaneously in the real samples. Scheme 1 indicates the

fabrication processes of EDDPT/GO/CPE sensor and its using for simultaneous determination of

EP, AC and DA.

Scheme. 1 Schematic representation of the EDDPT/GO/CPE for simultaneous

determination of EP, AC and DA.

2.5. Preparation of real sample for analytical performance

The epinephrine solution was prepared by dissolving an ampule vial (100.0 mg) in 50 mL

phosphate buffer solution (pH 7.0) using an ultra-sonication. After adjusting the pH, further

dilution was also done to reach the calibration range of EP. The serum sample was centrifuged

for 10 min and then diluted with phosphate buffer solution (pH=7.0). Ten mL of solution was

transferred into the voltammetric cell to be analyzed without any further pretreatment.

7
3. Results and Discussion

3.1 The characterization of synthesized graphene oxide and surface studies

The synthesized graphene oxide (GO) was characterized with FT-IR and UV/Vis

spectroscopy methods. As shown in Fig. 2A, the FT-IR spectrum of GO reveals a C-O stretch at

1222 cm-1, a O-H stretch at 3500–3300 cm-1, and a C =O stretch at 1720–1690 cm-1 [41] . The

UV/vis absorption spectrum of GO indicates strong absorption band attributed to π-π* transitions

of aromatic C=C bonds. According to Fig. 2B, the prepared GO contains two characteristics

bands: a strong absorption band with a maximum at 228 nm and a shoulder at around 300 nm

[42].

Fig. 2 A) FT-IR spectrum of GO, B) UV/vis absorption spectrum of GO.

The morphology of bare CPE and GO/CPE was investigated by scanning electron

microscopy (SEM). As shown in Fig. 3A, the SEM image of CPE shows that carbon paste

8
electrode has a surface which formed by irregularly shaped flakes of graphite. There are some

petal-like graphene nano sheets with sharp edges and random directions with a large surface area

in the SEM image of GO/CPE (see Fig. 3B). The obtained SEM images of GO indicate that the

modification of CPE with GO is performed well which can lead to an increase in the surface area

and consequently enhancing the sensitivity in determination of analyte.

Fig. 3 The SEM images of A) CPE and B) GO/CPE

3.2. The electrocatalytic oxidation of EP at EDDPT/GO/CPE sensor

To investigate electrocatalytic oxidation of EP at EDDPT/GO/CPE electrode, CV responses of

50.0 µM EP at the bare CPE (curve a), GO/CPE (curve b), EDDPT/CPE (curve c),

EDDPT/GO/CPE (curve d) were obtained while the curves e and f are related to CPE and

EDDPT/CPE in the buffer solution in the absence of EP, respectively. As it is seen in Fig. 4, the

comparison of curves a and b shows an increase in the anodic peak current of GO/CPE (curve b)

compared with the bare CPE, which is due to the presence of GO in CPE with excellent

9
characteristics of graphene oxide sheets. Also, the anodic peak potential for EP at the bare

carbon paste electrode is 0.437 V (curve a), while the obtained potential at EDDPT/GO/CPE is

about 158 mV (Fig. 4 curve d). So, the comparison of these curves reveals that the peak potential

of EP oxidation at EDDPT/GO/CPE shifts about 279 mV towards a negative value as compared

with the bare CPE. Also, in the presence of EP, the anodic peak current of the modifier (EDDPT)

is increased and the cathodic peak of the mentioned modifier is removed. Through these results,

an EC' catalytic mechanism is offered for EP oxidation at the surface of EDDPT/GO/CPE

sensor. As an effective parameter, the pH parameter, was investigated on the electrocatalytic

oxidation of EP, too. The inset of Fig. 4 reveals a maximum current for pH between =7.0 to 8.0

for the electro catalysis of EP. The electrochemical oxidation of EP in pHs more than 8.0 makes

a decrease in the oxidation peak current, which is probably due to protonation of OH groups onto

the modifier (EDDPT) or the amine group of EP. Thus, pH=7.0 was selected as an optimum pH

due to being as a biologic pH in human.

Fig. 4 Cyclic voltammograms of a 0.1 M phosphate buffer solution (pH 7.0) containing 50.0 µM

EP at (a) unmodified CPE, (b) GO/CPE, (c) EDDPT/CPE, (d) EDDPT/GO/CPE, (e) cyclic

10
voltammograms of unmodified CPE and (f) EDDPT/GO/CPE in a 0.1 M phosphate buffer

solution without EP. In all the cases, the scan rate is 30 mV s -1. Inset: Variation of anodic peak

current of EDDPT vs. pH in the presence of EP in a phosphate buffer solution and scan rate of 30

mVs-1

3.3. Chronoamperometric studies

Chronoamperometric measurements of EP were performed at the EDDPT/GO/CPE

sensor by setting the potential of mentioned electrode at 0.280 V for different concentrations of

EP (Fig. 5). The diffusion coefficient of EP at EDDPT/GO/CPE was calculated by

chronoamperometric studies. The obtained slope of the linear region of the Cottrell’s plot current

can lead to determination of the diffusion coefficient (D) of EP (Fig. 5, inset A). In this study, the

mean value of diffusion coefficient was calculated to be 7.70 × 10-6 cm2 s-1. Also, the catalytic

rate constant, k, from the reduced form of Galus was investigated by following equation [43].

ICat/IL = π1/2γ1/2 = π1/2(KCbt)1/2

where the components of equation are described as: IC is the catalytic current of fabricated

electrode in the presence of EP, I L is the limited current in the absence of EP, and Cb is the bulk

concentration of EP. By plotting IC/IL versus t1/2 and the obtained slope of this plot, the value of k

(796.0 M-1 s-1) was calculated for a specific concentration of EP at the surface of

EDDPT/GO/CPE sensor. The calculated value of k explains the sharp feature of the catalytic

peak observed for the catalytic oxidation of EP at the surface of EDDPT/GO/CPE.

11
Fig. 5 Chronoamperograms obtained at EDDPT/GO/CPE in a 0.1 M PBS (pH 7.0) for various

concentrations of EP (0.25 to 0.85 mM). Insets: (A) plots of I vs. t -1/2 obtained from the

chronoamperogram data and (B) plot of the slope of the straight lines against the EP

concentrations.

3.4. Optimization of the experimental parameters

To increase the sensitivity and selectivity of the EDDPT/GO/CPE sensor, the

experimental conditions including the percentages of EDDPT as a modifier, the value of GO in

12
CPE and the pH of solution were optimized. The influence of EDDPT present in CPE structure

on the oxidation peak current of EP was studied in the range of 0.25 to 3 % w/w at the scan rate

of 30 mVs-1 (six percent of DHPMP (0.25, 0.5, 1, 2, and 3% w/w) was examined). Due to the

obtained results 1.0 % w/w of EDDPT was selected as an optimum value.

The second parameter (the percentages of nano-material of GO in the structure of CPE) was

optimized and according to the obtained results, the optimum percentage of GO nanoparticles

was chosen to be 3%. It must be mentioned that by increasing percentages of GO, the value of

the peak current is increased and after 3%, it will be constant.

The last parameter optimized in this study, was the optimization of pH for further investigations.

According to inset of Fig. 4, the oxidation peak current of EP is increased from pH 2.0 to 7.0 and

then decreased at higher pH 8.0, therefore pH 7.0 was selected as an optimum pH for other

experiments.

3. 5. The sensitivity investigation of epinephrine by DPV technique

In this paper, the differential pulse voltammetry method DPV technique was applied for

determination of EP due to the better resolution of this technique than other electrochemical

techniques. The responses of peak current towards EP concentrations were linear in two linear

range by a calibration equation of ∆I (μA) = 0.22 CEP (μM) + 2.38 and regression coefficient of

r2= 0.9969 in the first segment and a calibration equation of ∆I (μA) = 0.0758 CEP (μM) + 6.284

and regression coefficient of r2= 0.9942 in the second segment. The detection limit for EP based

on 3sb/m (where sb is the standard deviation of a blank solution and m is the slope of the

calibration curve) was estimated to be 0.65 µM. The characteristics of the proposed electrode

was compared with those from other previously reported studies for determination of EP in Table

1 [44-47].The obtained results indicate that the linear range (1.5–600.0 μM) and detection limit

13
(0.65 µM) obtained in this work are suitable for determination of EP (Table 1). The obtained

wide linear range and low detection limit for determination of EP can be related to using GO

nano sheets with unique mentioned properties in the structure of EDDPT/GO/CPE senor.

3.6. Investigation of chemical interferences

The tolerance limit was taken as the maximum concentration of the foreign substances,

which caused an approximately ±5% relative error in the determination. The influence of various

species was examined to investigate the selectivity of the designed sensor towards EP (50.0 µM).

Some cations and anions such as Na+, Cl-, Mg2+, K+, Mg+2 up to molar ratio of 1000 had no

interference effect on oxidation peak current of EP. Also, some compounds such as glucose,

fructose and folic acid up to molar ratio of 50 had no interference effect on the EP peak current.

3.7. Simultaneous determination of EP, AC and DA

As known, it has not been reported any papers for the simultaneous determination of EP, AC

and DA using EDDPT/GO/CPE. So, the simultaneous determination of EP, AC and DA was

performed at EDDPT/GO/CPE sensor. Differential pulse voltammetry technique and the various

concentrations of EP, AC and DA were used. According to Fig. 6, a three well-distinguished

anodic peaks at potentials of 148, 340 and 631 mV corresponding to the oxidation of EP, AC and

DA, respectively is revealed. As shown in this figure, using EDDPT/GO/CPE sensor can cause

the separation of the anodic oxidation peaks of three mentioned compounds and consequently

determination of EP, AC and DA simultaneously. Also the insets of A, B and C of Fig. 6 indicate

the calibration curves related to EP, AC and DA, respectively. It is noticeable that the

14
sensitivities of the modified electrode to EP in the absence (∆I (μA) = 0.0762 CEP (μM) + 6.284)

and presence of AC and DA (∆I (μA) = 0.0754 CEP (μM) + 6.573) are virtually close which

indicates that the oxidation processes of EP, AC and DA at EDDPT/GO/CPE are independent.

Therefore, simultaneous or independent measurements of three analytes are possible without any

interference.

15
Fig. 6 DPVs of EDDPT/GO/CPE in a 0.1 M PBS (pH 7.0) containing different concentrations of

EP (50-400 µM), AC and DA with concentrations of (100 to 600 µM) and the repetitive number

of experiments is five (n=5). Insets: A) plot of the peak current as a function of EP concentration,

B) Plot of the peak current as a function of AC concentration and C) Plot of the peak current as a

function of DA concentration.

3.8. Reproducibility and stability of EDDPT/GO/CPE

To investigate the reproducibility, five independent EDDPT/GO/CPE sensors were

prepared on the same day and under optimum conditions. Then, prepared modified electrodes

were used for determination of 100.0 µM EP solution by DPV method. A relative standard

deviation (RSD) of 3.1% for oxidation peak current of EP solution was obtained that

demonstrates a high reproducibility of EDDPT/GO/CPE sensor. Also, the stability of the

modified electrode was examined for 7 days, after storing the modified electrode at room

temperature, the obtained DPVs showed that the peak potential for EP oxidation retained about

92% of its initial response after 7 days which indicates suitable stability of the designs sensor.

3.9. Analytical performance

In order to assess the analytical application of this method, the catalytic oxidation of EP

in the real samples was tested. In this paper, we examined the oxidation of EP in a drug sample

(epinephrine ampule) with the voltammetric determination of EP. The examination was

performed with the multi-point standard addition to remove matrix effect. From the extrapolation

of the plot, the average amount of EP in the ampule was obtained 96 mg with a recovery of 96%,

which has a good agreement with the nominal value of the ampule label (100.0 mg). Also, for

16
investigation of the applicability of EDDPT/GO/CPE sensor for simultaneous determination of

EP, AC and DA in real samples, EDDPT/GO/CPE sensor was applied in the serum solutions.

The serum sample was prepared as explained in experimental section. The results are listed in

Table 2 and these results indicate good recovery percentages of EP, AC and DA in the diluted

serum solutions using EDDPT/GO/CPE sensor which have good agreement for spiked EP, AC

and DA values. So, these results indicate that EDDPT/GO/CPE sensor is applicable for

simultaneous determination of EP, AC and DA in biologic samples as well as determination of

EP individually.

4. Conclusions

This work reports the fabrication of an epinephrine sensor based on a carbon paste

electrode with graphene oxide nano sheets and a hydroquinone derivative (EDDPT) as modifier

(EDDPT/GO/CPE). The CV and DPV results revealed that the oxidation of EP is catalyzed by

the mediator (EDDPT) at pH 7.0, and the peak potential of EP is shifted by 279 mV to a less

positive potential at the surface of EDDPT/GO/CPE sensor. Some advantages of the designed

sensor are possessing low detection limit (0.65 µM) and wide linear range (1.5–600.0 μM) due to

using nanosheets of graphene oxide in the structure of the designed sensor which can lead to an

increase in the effective surface area and consequently obtaining a low detection limit. Also, the

sensitive and selective sensor with high reproducibility and stability was applied successfully for

simultaneous determination of EP, AC and DA. We hope that our present work leads to

improving the fabrication of some new electrochemical sensors for determination of different

species.

Acknowledgement

17
 We gratefully acknowledge the support of this work by the Yazd University research council

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24
Table 1 Comparison of the proposed method with some previously reported electrochemical

methods for determination of EP

Linear range Detection

Electrode Modifier pH Ref
(µM) limit (µM)
2,20-[1,2-
CNTs/ CPE ethanediylbis(nitrilomethylidyne)]- 7.0 5.0-600.0 1.0 [44]
bishydroquinone
Gold
l-cysteine self-assembled - 1.0 - 18.0 0.01 [45]
electrode
3,4-dihydroxybenzaldehyde-2,4-
CPE Dinitrophenylhydrazone, carbon 7.0 0.10-750.0 2.80 [46]
nanotubes
CPE MWCNTs 7.0 0.05-100.0 0.029 [47]
This
CPE EDDPT/GO 7.0 1.5-600.0 0.65
work

25
Table 2. Simultaneous determination of EP, AC and DA in the diluted serum solution using

EDDPT/GO/CPE

Number

Sample spiked (µM) Found (µM) Recovery (%) RSD (%)

EP AC DA EP AC DA EP DA AC EP AC DA

1 100 50 50 98 48 48 98 96 96 1.21 1.1 1.5

2 200 100 100 202 95 105 101 95 105 2.19 1.9 2.2

3 300 200 200 285 208 194 95 104 97 3.4 2.5 1.1

26
Graphical Abstract

In this work, the fabrication of EDDPT/GO/CPE sensor for EP determination was reported. Some
advantages of the proposed electrode are possessing easy preparation, low detection limit (0.65 µM),
wide linear range (1.5–600.0 μM) and application of the mentioned electrode for simultaneous
determination of EP, AC and DA species.

27
Highlights:

1- Fabrication of an epinephrine sensor using CPE modified with GO and a modifier

2- Simultaneous determination of epinephrine, acetaminophen and dopamine by

EDDPT/GO/CPE

3- The proposed sensor showed high sensitivity, repeatability and high stability

4- The applicability of the proposed sensor in tablet and serum solutions samples

28