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Open Access
BMC Chemistry
Voltammetric approach forpharmaceutical
samples analysis; simultaneous quantitative
determination ofresorcinol andhydroquinone
Ebrahim Nabatian1,2, Mahdi Mousavi2, Mostafa Pournamdari3, Mehdi Yoosefian4* and
Saeid Ahmadzadeh5,6*
Abstract
A simple and precise analytical approach developed for single and simultaneous determination of resorcinol (RC) and
hydroquinone (HQ) in pharmaceutical samples using carbon paste electrode (CPE) modified with 1-Ethyl-3-meth-
ylimidazolium tetrafluoroborate as ionic liquid and ZnFe2O4 nanoparticle. A significant enhancement in the peak
current and sensitivity of the proposed sensor observed by using modifiers in the composition of working electrode
compared to bare CPE which is in accordance with the results obtained from electrochemical impedance spectros-
copy investigations. Electrochemical investigations revealed a well-defined irreversible oxidation peak for RC over a
wide concentration range from 3.0 µM to 500 µM in 0.1 M phosphate buffer solution (pH 6.0) with the linear regression
equations of Ip (µA) = 0.0276 CRC (µM) + 0.5508 (R2 = 0.997). The limit of detection and quantification for RC analysis
were found to be 1.46 µM and 4.88 µM, respectively. However, the obtained SW voltammograms for simultaneous
determination of RC and HQ exhibited a desirable peak separation of about 360 mV potential difference and a satis-
factory linear response over the range of 50–700 µM and 5-350 µM with the favorable correlation coefficient of 0.991
and 0.995, respectively. The diffusion coefficient (D) of RC and the electron transfer coefficient (α) at the surface of
ZnFe2O4/NPs/IL/CPE estimated to be 2.83 × 10− 4 cm s− 1 and 0.76. The proposed sensor as a promising and low-cost
method successfully applied for determination of RC in commercial pharmaceutical formulations such as the resor-
cinol cream of 2% O/W emulsion available on the market with the recovery of 98.47 ± 0.04.
Keywords: Resorcinol, Hydroquinone, Voltammetric analysis, Pharmaceutical samples, Modified carbon paste
electrode
Introduction
Dihydroxybenzenes as the important phenolic com-
pounds with high toxicity and low degradability sus-
pected of being carcinogens extremely released into the
environmental mediums since they used as the chemical
intermediate for the synthesis of the variety of pharma-
ceuticals and other organic compounds such as dyes,
photography chemicals, plastics, flavoring agents, anti-
oxidant, rubber, and pesticides. erefore, they listed as
priority pollutants by environmental organizations such
as US-EPA and EU [1, 2].
Resorcinol (RC, 1,3-dihydroxybenzene) and hydroqui-
none (HQ, 1,4-dihydroxybenzene) as two pharmaceutical
products extensively used for the treatment of skin dis-
eases. RC commonly applied for acne medication and the
treatment of chronic skin diseases such as psoriasis and
hidradenitis suppurativa [3, 4]. However, due to its toxic
*Correspondence: myoosefian7@gmail.com; saeid.ahmadzadeh@kmu.ac.ir;
chem_ahmadzadeh@yahoo.com
4 Department of Chemistry, Faculty of Chemistry and Chemical Engineering,
Graduate University of Advanced Technology, Kerman, Iran
6 Pharmaceutical Sciences and Cosmetic Products Research Center,
Kerman University of Medical Sciences, Kerman, Iran
Full list of author information is available at the end of the article
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Page 2 of 12
Nabatianetal. BMC Chemistry (2022) 16:115
effect at the higher doses, RC disrupts the function of the
nervous system which causes acute respiratory problems
as well as the endocrine system such as thyroid gland
function. On the other hand, HQ as a skin whitening
product inhibits the enzymatic pathway of tyrosinase for
producing pigment melanin from dopamine [5, 6]. Due
to the extraordinary toxicity of HQ at high concentration,
it causes nausea, edema of internal organs, headache,
dizziness, and even kidney damage in humans [3, 7].
In order to discriminate the two mentioned dihydroxy-
benzene isomers RC and HQ with similar properties and
structure, numerous analytical procedures employed
including chromatography [8], fluorescence [9], spectro-
photometry [10], fluorometry [3], chemiluminescence
[4], and electrochemical methods [3, 6, 7] .
Most of the mentioned instrumental methods are
time-consuming, costly; require complicated sample
preparation and expert operator which is not suitable for
routine analysis. In contrast, the electrochemical tech-
niques received extraordinary attention due to their low
cost, rapid response, easy operation, low detection limit,
and relatively short analysis time [11, 12]. Recently a
few modified electrochemical sensors developed for the
simultaneous determination of RC and HQ in biological
and pharmaceutical samples [3–7]. However, they suf-
fered from the narrow dynamic concentration range and
an undesirable lower detection limit.
Among the modified electrodes, carbon paste elec-
trodes (CPEs) received extraordinary attention due to the
advantages of easy preparation and renewability, gener-
ous surface chemistry, stable response, wide potential
window and low ohmic resistance. In addition to all the
benefits mentioned, the use of modifiers that effectively
accelerate and facilitates the electron transport between
the analyte and the electrode has made the modified
carbon paste electrodes a suitable candidate for simulta-
neous measurement of the analytes by reducing the over-
potential required for the electrode reactions [13, 14].
To improve the electrochemical conductivities of bare
CPE, room temperature ionic liquid and synthesized
nanoparticles namely 1-ethyl-3-methylimidazolium
tetrafluoroborate and ZnFe2O4 used as the modifiers
to form a stable carbon paste composite in the current
work, respectively. e unique physicochemical char-
acteristics of the mention materials resulted in a better
electrochemical response of the modified CPE particu-
larly for the quantitative determination of trace analytes
[15, 16]. Ionic liquids (ILs) with remarkable chemical and
thermal stability, acceptable electrochemical windows
and desirable ionic conductivity properties received con-
siderable attention in modifying the CPEs. ILs provide
benefits such as improving the electron transfer rate,
sensitivity, and conductivity of the modified CPEs com-
pared to bare CPEs [17]. On the other hand, to provide
a larger active surface area with desired catalytic activ-
ity for facilitating the electron transport between the
analyte and modified CPEs surface, metal nanoparticles
extensively applied in the fabrication of electrochemical
sensors [18, 19]. Moreover, metal nanoparticles as an effi-
cient catalyst enhanced the electrochemical reactions of
electrochemical sensors and biosensors [8, 20–22].
erefore, herein great attempts have been done to
develop a highly selective and sensitive sensor for quan-
titative determination of trace amount of RC in commer-
cial pharmaceutical formulations available on the market
using the proposed modified CPE. To the best of our
knowledge, for the first time a square wave voltammetric
method developed for simultaneous determination of RC
and HQ in the current work. e proposed sensor as a
promising and low-cost method successfully applied for
determination of RC in commercial pharmaceutical for-
mulations such as the resorcinol cream of 2% O/W emul-
sion available on the market.
Experimental
Chemicals andreagent
Analytical grade resorcinol (RC), iron (III) chloride hexa-
hydrate (FeCl3·6H2O), zinc (II) chloride (ZnCl2), sodium
hydroxide (NaOH), sodium bicarbonate (NaHCO3),
calcium sulfate (CaSO4), magnesium nitrate hexahy-
drate (Mg(NO3)2·6H2O), potassium carbonate (K2CO3),
1-ethyl-3-methylimidazolium tetrafluoroborate (IL),
graphite fine powder extra pure, and extra pure paraffin
obtained from Sigma-Aldrich. Glucose, ascorbic acid,
phenylalanine, methionine, alanine, valine, isoleucine,
urea, and thiourea obtained from Merck. Phosphate
buffer solutions (PBS) with the desired pH values pre-
pared using 0.1 M H3PO4 and 0.1 M NaOH solutions.
Instruments
e applied electrochemical compartment consisted of a
conventional three-electrode system including ZnFe2O4/
NPs/IL/CPE, platinum wire, and Ag/AgCl (3 M KCl) as
working, counter, and the reference electrode, respec-
tively. Electrochemical investigations carried out by
Autolab PGSTAT204-Metrohm potentiostat/galvanostat
programmed and controlled by NOVA 1.11 software and
equipped with FRA module for electrochemical imped-
ance spectroscopy studies.
All experiments carried out at room temperature.
e pH adjustment performed by a Metrohm pH meter
model 827 pH lab (Metrohm AG, Switzerland). To
evaluate the morphological aspects of the synthesized
ZnFe2O4 nanoparticle, field emission scanning electron
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Page 3 of 12
Nabatianetal. BMC Chemistry (2022) 16:115
microscopy (FE-SEM) X-Ray Diffraction (XRD), and
UV-Vis spectroscopy analysis carried out using TES-
CAN MIRA3 XMU FE-SEM and Panalytical X’Pert Pro
MPD X-Ray Diffraction System, and Optizen 3220 UV
spectrophotometer, respectively,
Nanoparticle synthesis procedure
e aqueous solutions of 0.4 M iron chloride
FeCl3·6H2O, 0.2 M zinc chloride ZnCl2 prepared in
distilled water. e volume of 25 mL of each solution
mixed to each other in Erlenmeyer flask under stirrer
300 rpm condition. Afterward, 25 mL of 3.0 M NaOH
solution as the precipitating agent added dropwise to
the above solution using burette under same stirrer
condition where the gradual formation of precipitate
observed. e obtained colloidal solution which syn-
thesized by chemical coprecipitation method, filtered
and the pH of the precipitate adjusted at 7.0 by washing
with distilled water. Moreover, to improve the nuclea-
tion and growth of nanoparticles in the proposed solu-
tion, microwave heating and reflux process applied
in the current work as follow. 25 mL of aqueous solu-
tion containing the collected precipitate placed in the
microwave for 30 min at 600 watts. e pH of the solu-
tion adjusted at 7.0 by adding required amount of 0.5 M
NaOH solution. e obtained precipitate dried at room
temperature overnight. Subsequently, the reflux process
carried out for the obtained precipitate in the presence
of H2O:EtOH (1:2) binary solvent for 45 min. finally, the
achieved precipitate filtered and its pH adjusted at 7.0
using distilled water and dried at room temperature for
24 h.
Electrode modication procedure
To prepare the ZnFe2O4/NPs/IL/CPE, an optimized
proportion of 0.1 g synthesized ZnFe2O4 nanoparti-
cles and 0.9 g graphite powder mixed with abrasion
in a mortar. To ensure the uniformity of the resulting
mixture, ethyl ether as a highly volatile and ineffective
solvent added to the mixture. e mixing process con-
tinued until the solvent evaporated completely. en,
an optimized proportion of 0.2 g 1-Ethyl-3-methylim-
idazolium tetrafluoroborate as ionic liquid and 0.8 g
paraffin was added to the mixture dropwise, and after
each drop, the mixture mixed with mortar to obtain
a uniform paste. An appropriate portion of the pre-
pared paste injected into a glass tube and connected to
the electrochemical workstation by a copper wire. To
achieve a perfectly flat and uniform surface of the work-
ing electrode, the paste pushed by wire and the end of
the glass tube polished on a glossy sheet of paper.
Results anddiscussion
Characterization ofthesynthesized ZnFe2O4 nanoparticle
To evaluate the successful synthesis of ZnFe2O4 nanopar-
ticle, FE-SEM, XRD and UV-Vis techniques employed.
Field emission scanning electron microscopy (FE-SEM)
with high-resolution operating at 15 KeV accelerat-
ing voltage applied to investigate the surface details and
morphology of the synthesized ZnFe2O4 nanoparticle. As
demonstrated in Fig.1A, a three-dimensional nanostruc-
ture with a high surface area obtained. According to the
obtained micrograph, the ZnFe2O4 nanoparticles exhibit
a typical homogeneous morphology with a spherical
structure which aggregate to some extent. It concluded
that the enhancement in peak current of modified carbon
paste electrode attributed to the increase in the active
surface area of the working electrode due to the usage of
the ZnFe2O4 nanoparticle.
e XRD analysis performed from 2.0° (2θ) to 80.0°
(2θ) and the diffraction data analyzed using PDF2 data-
base. As seen from the XRD patterns of ZnFe2O4 nano-
particle presented in Fig.1C, the diffraction peaks at 2θ
of 30.06°, 35.45°, 43.03°, 53.54°,57.16°,62.72°,and 73.99°
with the calculated d-spacings of 0.297 nm, 0.253 nm,
0.210 nm, 0.171 nm, 0.161 nm, 0.148 nm, and 0.128 nm
can be assigned to (220), (311), (400), (422), (511), (440),
and (533) reflection planes of the regular spinel cubic
structure of ZnFe2O4 with the space group of Fd3m
(JCPDS No. 77–0011), respectively. To calculate the
size of the synthesized nanoparticle, the Scherrer equa-
tion employed. e average size of 15 nm obtained for
ZnFe2O4 nanoparticle using the peak corresponding to
(311) reflection plane.
On the other hand, UV-Vis spectroscopy applied to
evaluate the particle size of the synthesized nanoparticle.
e absorbance recorded at the wavelength from 250 to
600 nm with 5 nm step size. As seen from the obtained
absorption spectra in Fig.1B, the maximum absorption
Table 1 The effect of some coexisting substances on the
determination of 50 µM resorcinol (n = 3)
Species Tolerance limits (W/W: n-fold excess
weight of interference vs. resorcinol)
HCO3−, Ca2+, Mg2+, Na+, K+,
SO42−, CO32−, NO3−
500
Glucose 500
Ascorbic acid 200
Phenylalanine, methionine,
alanine, valine, isoleucine 700
Urea, thiourea 400
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Page 4 of 12
Nabatianetal. BMC Chemistry (2022) 16:115
peak achieved at 350 nm. e average particle size of the
synthesized ZnFe2O4 nanoparticle calculated using the
equation expressed as follow [23]:
e calculated particle size was found to be 13.5 nm
which is in excellent accordance with the obtained size
from FE-SEM and XRD analysis.
Electrochemical behavior ofRC indierent pH
According to the Nernst equation, the pH of the electro-
lyte solution and the existence of proton play an impor-
tant role in the intensity of the oxidation process of
electro-active species. erefore, the effect of solution pH
on the electrochemical oxidation of RC investigated. e
pH of the electrolyte solution was changed from 4 to 9
using 0.1 M PBS and the oxidation peaks of RC (500 µM)
recorded applying ZnFe2O4/NPs/IL/CPE. e obtained
results revealed that the potential of the oxidation peak
(1)
Particle size
(nm)=−0.2963 +(−40.1970 +13,620
p
−7.34 +2418.6
p
2
shifted to less positive values by increasing the solution
pH which indicated that the proton involved in the elec-
trocatalytic oxidation of RC (see Fig.2A). As it is obvious,
the value of anodic peak current enhanced by increasing
the solution pH from 4 to 6, however, for further increase
in solution pH from 6 to 9, a decrease in the value of
anodic peak current observed [24]. Accordingly, the opti-
mum solution pH of 6 with the maximum amount of the
oxidation current was selected as the ideal buffer solution
and applied throughout the current work.
By plotting the peak potential (Ep.a. in V) versus the
solution pH a straight line with the linear regression
equation of Ep (V) = − 0.0585 pH + 1.1213 (R2 = 0.9863)
obtained (see Fig.2B). By comparing the obtained slope
of 0.0585 with the Nernstian slope of 0.0591m/n, where
m and n denote the number of protons participated and
electron transferred through the electrochemical reac-
tion, it can be concluded that the number of protons and
electrons that involved in the oxidation process of RC are
equal. In accordance with the evidence presented above,
the Scheme1 could be suggested as the oxidation mecha-
nism of RC (Scheme1).
Improvement ofmodied CPE electrochemical
performance
To investigate the electrocatalytic effect of modifica-
tions process on the characteristics performance of the
applied carbon paste electrode in the current work, the
proposed bare electrode modified over several steps [25].
All investigations conducted with the optimum value of
pH solution 6 in 0.1 M PBS at the scan rate of 100 mV s− 1
Table 2 Determination of RC in resorcinol cream of 2% O/W
emulsion available on the market by the proposed sensor
Resorcinol
cream of
2% O/W
emulsion
Obtained
oxidation
peak
current*(µA)
Measured
concentration
(mg)
Recovery % W/W
Resorcinol
1 g 1.81 19.12 98.47 ± 0.04 % 1.9
Table 3 Comparison of the analytical performance of the proposed sensor for the simultaneous determination of RC and HQ with
other electrochemical sensors found in the literature
a Gold nanoparticle–graphene nanohybrid bridged 3-amino-5-mercapto-1,2,4-triazole-functionalized multiwall carbon nanotubes
b Porous reduced graphene oxide
c Naon/multi-walled carbon nanotubes/carbon dots/multi-walled carbon nanotubes
d multielectrode array modied with multiwall carbon nanotubes
e Polyaniline (PANI) nanobers / MnO2 modied electrode
f Graphene Doped Carbon Ionic Liquid Electrode
Electrode (specicity) Technique
(specicity) pH Linearity and Range (µM) LOD (µM) Refs.
HQ RC HQ RC
MWCNT–SH@Au–GR/GCE aDPV 7 54.5–1250.5 43.5–778.5 4.17 7.80 [3]
P-rGO bDPV 7 5–90 5–90 0.08 2.62 [30]
Nafion/MWCNTs/CDs/MWCNTs cDPV 7 1–200 1–400 0.07 0.15 [7]
MEA-MWCNTs dAmperometry 5.40 1–100 6–100 0.3 0.6 [3]
PANI/MnO2 ME eDPV 7 0.2–100 0.2–100 0.13 0.09 [5]
Graphene doped CILE fDPV 5 10–400 1–170 1.8 0.4 [6]
ZnFe2O4/NPs/IL/CPE SWV 6 50–700 3.0-500 23.5 1.46 Current work
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Page 5 of 12
Nabatianetal. BMC Chemistry (2022) 16:115
in the presence of 500 µM RC using cyclic voltammetry
technique. e RC oxidation peak potential was found to
be around 780 mV with the peak current of 22.3 µA by
applying the bare CPE. However, optimizing the cata-
lytic ability of CPE ingredients by adding a fraction of
nanoparticles and ionic liquid instead of graphite powder
and paraffin, respectively, revealed a substantial increase
on the surface conductivity of the applied CPE which
resulted in enhancement of oxidation current along
with shifting the oxidation potential to a more negative
value. As seen from Fig.3A, the overvoltage of RC oxi-
dation process decreased on the surface of CPE, IL/CPE,
ZnFe2O4/NPs/CPE, and ZnFe2O4/NPs/IL/CPE (curves
a–d, respectively). As a result, the recorded RC oxidation
peak on the surface of ZnFe2O4/NPs/CPE exhibited sig-
nificant oxidation current of 35.5 µA around 765 mV.
Furthermore, the surface current density of the men-
tioned electrodes calculated from the obtained related
oxidation peak current and demonstrated in Fig. 3B.
e obtained results revealed that the applied modi-
fiers resulted in enhancement of active surface area of
proposed electrodes which is in accordance with the
conducted electrochemical impedance spectroscopy
investigations [26].
(A
)(
B)
0
0.1
0.2
0.3
0.4
0.5
0.6
250350 450550 650
Absorbance
Wave length(nm)
(C)
Fig. 1 A FE-SEM image of ZnFe2O4 nanoparticles. B UV-Vis absorption spectra of ZnFe2O4 nanoparticles. C Representative XRD pattern of ZnFe2O4
nanoparticles
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Nabatianetal. BMC Chemistry (2022) 16:115
Electrochemical impedance characterization
Electrochemical impedance spectroscopy (EIS) as a
dominant diagnostic tool applied for characterization
of the interface structure of electrolyte solution/elec-
trode and the electrode surface nature. Herein, EIS as an
experimental technique used for describing the observed
changes in characteristic performance of carbon paste
electrode throughout its modification process using
ZnFe2O4/NPs and 1-Ethyl-3-methylimidazolium tetra-
fluoroborate as the binder.
e EIS investigations conducted over the frequency
range of 10− 2 to 105 Hz. As seen from Fig. 4A, the
obtained Nyquist plots for CPE, ZnFe2O4/NPs/CPE, IL/
CPE and ZnFe2O4/NPs/IL/CPE revealed that by modi-
fying the CPE, the diameter of the semicircle portion at
higher frequency which corresponds to the charge trans-
fer limited process decreased and indicated that the elec-
tron transfer resistance on the surface of the proposed
electrodes gradually diminished and accordingly, the
highest charge transfer rate observed at the surface of
ZnFe2O4/NPs/CPE.
e linear part of the Nyquist plot at lower frequency
represent the limited diffusion process. e values of the
charge transfer resistance for CPE, ZnFe2O4/NPs/CPE,
IL/CPE and ZnFe2O4/NPs/IL/CPE found to be 16.30 kΩ,
11.30 kΩ, 9.06 kΩ, and 5.25 kΩ, respectively.
e equivalent circuit of Fig.4B obtained by modeling
the impedance data of Nyquist plots in the term of an
electrical circuit. e proposed equivalent circuit con-
stituted of Rs denotes the electrolyte solution resistance
in series with the parallel circuit of Zf and Cdl denote the
Faradaic impedance and the double layer capacitance,
respectively. Zf composed of two parameters including
Rct and Zw denote the charge transfer resistance and the
Warburg impedance, respectively.
Characterization ofscan rate eect
To investigate the nature of the RC oxidation and its
kinetic parameters at ZnFe2O4/NPs/IL/CPE, the rela-
tionship between the potential scan rate and peak
current over the range of 5-900 mV/s studied in the
presence of 500 µM of RC, using cyclic voltammetry.
As seen from the voltammograms in Fig.5A increasing
-5
4
13
22
31
40
49
00.2 0.40.6 0.811.2
Current (µA)
Potential (V) vs. Ag/AgCl
d
e
f
a
b
c
y = -0.0585x + 1.1213
R² = 0.9863
0.5
0.6
0.7
0.8
0.9
1
345678
91
0
Potential (V) vs. Ag/AgCl
pH
B
A
Fig. 2 A Cyclic voltammetric curves of 500 µM RC on the surface
of ZnFe2O4/NPs/IL/CPE at different pH values of phosphate buffer
solution (PBS): 4(a), 5(b), 6(c), 7(d), 8(e), and 9(f). B Peak potential
dependence on solution pH for RC oxidation on the surface of
ZnFe2O4/NPs/IL/CPE
-5
7
19
31
43
55
0.20.4 0.60.8
11
.2
Current (µA)
Potential (V) vs. Ag/AgCl
a
b
c
d
A
0
100
200
300
400
500
600
Current density (µ
µ
A cm
-2
)
Kind of electrode
abcd
B
Fig. 3 A Cyclic voltammetric curves of 500 µM RC in PBS (0.1 M) pH 6
on the surface of (a) ZnFe2O4/NPs/IL/CPE, (b) IL/CPE, (c) ZnFe2O4 /NPs
/CPE and (d) CPE at scan rate of 100 mV. s− 1. B The current densities
derived from cyclic voltammetric curves at the same electrodes
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Page 7 of 12
Nabatianetal. BMC Chemistry (2022) 16:115
the potential scan rate resulted in a gradual increase in
the oxidation peak current. However, the potential of
the oxidation peak shift towards more positive values
which indicated that the electro-oxidation of the RC
was irreversible.
As seen from Fig.5B, by investigating the relationship
between the anodic peak current intensity (Ip) vs. poten-
tial scan rate (ν) and the square root of potential scan
rate (ν1/2), it was found that a satisfactory linear relation-
ship between Ip and ν1/2 with a correlation coefficient of
0.993 observed which confirmed that the electrode pro-
cess of RC oxidation controlled by diffusion mechanism
at ZnFe2O4/NPs/IL/CPE [27]. e obtained correlation
equation expressed as below:
Alternatively, by plotting the Log Ip versus Log ν, the
electrode process regarding mass transport mechanism
can be specified. It is known that the slope values around
(2)
I
p(µ
A
)
=4.5689n1/2
(
mV1/2s−1/2
)
−
8.4357
R2
=
0.9928
0.5 denote the redox process controlled under the dif-
fusion step. However, the slope values around 1.0 indi-
cated that the redox processes ruled by adsorption. e
obtained result from Fig.5C was in accordance with the
recommended mechanism in the previous section.
0
5000
10000
15000
20000
25000
0800016000 2400032000 40000
Z
imaginary
(Ω)
Z
real
(Ω)
a
b
cd
A
Fig. 4 A Nyquist diagrams of (a) ZnFe2O4/NPs/IL/CPE, (b) IL/CPE, (c)
ZnFe2O4 /NPs /CPE and (d) CPE. Conditions: 500 µM RC in PBS (0.1 M)
pH 6, over the frequency range of 0.1 to 100,000 Hz. B Corresponding
equivalent circuits
-30
7
44
81
118
155
192
0.20.4 0.60.8 11.2 1.4
Current (µA)
Potential (V) vs. Ag/AgCl
5
900
A
y = 4.5689x -8.4357
R² = 0.9928
-5
25
55
85
115
145
0714 21 28 35
Current (µA)
(Scan rate)
1/2
(mV s
-1
)
1/2
B
y = 0.5792x + 0.3978
R² = 0.998
0.5
1
1.5
2
2.5
00.7 1.42.1 2.
83
.5
Log current(µA)
Log scan rate (mV s
-1
)
C
Fig. 5 A Cyclic voltammetric curves of the ZnFe2O4/NPs/IL/CPE at
different potential scan rates of 5, 15, 25, 50, 80, 100, 150, 250, 300,
400, 600, 800 and 900 mV s− 1 in PBS (0.1 M) pH 6 containing 500 µM
RC. B Peak current dependence on the square root of scan rate for
RC oxidation on the surface of ZnFe2O4/NPs/IL/CPE. C Relationship
between the logarithm of peak potential and logarithm of the
potential scan rate
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Nabatianetal. BMC Chemistry (2022) 16:115
To determine the electron transfer coefficient (α) of
the irreversible oxidation process of RC, the relation-
ship between the oxidation peak potential (E, V) and the
Naperian logarithm of the potential scan rate (Ln ν, V
s− 1) investigated. e obtained plot in Fig.6A, revealed
an adequate linear relationship with the regression equa-
tion expressed as follow:
According to the equation proposed by Nicholson
and Shain correspond to the graph of E (V) vs. Ln ν
(V.s− 1) expressed as follow, the value of electron trans-
fer coefficient (α) of 0.766 calculated from the slope of
the obtained plot which is m/2, where m is equal to RT/
[(1–α)nαF] .
(3)
E
p(V)=0.0275 Lnn
Vs−1
+0.8518
R2=0.9902
(4)
E
pa
=
E
0+
m
[
0.78
+
ln
D
1
2ks−
1−
0.5lnm
]+m
2
ln(ν
)
where Ep.a., E0, ν, and ks denote the oxidation peak poten-
tial, formal potential, potential scan rate, and the electron
transfer rate constant, respectively. Assuming the num-
ber of electrons involved through the electro-oxidation
process (n) is equal to 2. Furthermore, R, T, and F are
equal to 8.314 J mol− 1 K− 1, 298 K, and 96,485 C mol− 1,
respectively.
Additionally, via the data derived from the raising part
of the RC oxidation curve (current vs. potential), the
Tafel plot was developed [28]. As seen from Fig.6B, a
linear relationship between peak potential (Ep.a.) and the
logarithm of the peak current (Log I) with the satisfactory
correlation coefficient of 0.999 observed. e respective
equation expressed as below:
Herein, alternatively, the value of electron transfer coef-
ficient (α) can be calculated from the slope of the Tafel
plot which is equal to 2.303RT/[(1–α)nαF]. e electron
transfer coefficient value was found to be 0.783 which is
(5)
E
p(V)=0.136Log I(µA)+0.5051
R2=0.9998
y = 0.0275x + 0.8518
R² = 0.9902
0.65
0.7
0.75
0.8
0.85
0.9
-6 -5 -4 -3 -2 -1
01
Potential (V) vs. Ag/AgCl
Ln scan rate (V s
-1
)
A
y = 0.1368x + 0.5051
R² = 0.9998
0.57
0.58
0.59
0.6
0.61
0.62
0.63
0.64
0.50.6 0.70.8 0.
91
Potential (V) vs. Ag/AgCl
Log current (µA)
B
Fig. 6 A Nicholson and Shain’s plot of oxidation peak potential vs.
the Naperian logarithm of different potential scan rates of 5, 15, 25,
50, 80, 100, 150, 250, 300, 400, 600, 800 and 900 mV s− 1 in PBS (0.1 M)
pH 6 containing 500 µM RC. B Tafel’s plot of oxidation peak potential
vs. the logarithm of the peak current for the electro-oxidation of
500 µM RC on the surface of ZnFe2O4/NPs/IL/CPE at the scan rate of
25 mV s− 1 in PBS (0.1 M) pH 6 containing 500 µM RC.
0
70
140
210
280
350
420
0246810 12 14
Current (µA)
Time (s)
A
a
c
y = 40.92x -4.8734
R² = 0.9989
y = 64.004x -10.908
R² = 0.9989
y = 84.528x -12.977
R² = 0.9991
20
31
42
53
64
75
0.75 0.80.850.9 0.95 11.051.1
Current (µA)
(Time)
-1/2
(s
-1/2
)
a
b
c
B
Fig. 7 A Exponential single potential-step chronoamperometic
curves of 300 (a), 500 (b) and 700 (c) µM RC in PBS (0.1 M) pH 6. B
Cottrell’s plot of oxidation peak current vs. the minus square roots of
time for 300 (a), 500 (b) and 700 (c) µM RC in PBS (0.1 M) pH 6
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
Page 9 of 12
Nabatianetal. BMC Chemistry (2022) 16:115
in accordance with the obtained value for (α) from to the
graph of E (V) vs. Ln ν (V s− 1).
Chronoamperometric investigation
Chronoamperometry technique employed to assess the
diffusion coefficient (D) of RC at the surface of ZnFe2O4/
NPs/IL/CPE. e working electrode potential set at
1000 mV vs. the reference electrode. As seen in Fig.7A,
chronoamperograms recorded for three concentrations
of 300, 500, and 700 µM resorcinol in 0.1 M phosphate
buffer solution (pH 6.0).
rough the data derived from the mass transport lim-
ited part of the chronoamperogram curves, by plotting
the peak current (Ip) versus the minus square roots of
time (t− 1/2) the Cottrell plots obtained. As demonstrated
in Fig.7B, oxidation currents has a linear relation with
t− 1/2 at all three mention concentrations which con-
firmed that the mass transport mechanism at the surface
of working electrode controlled under the diffusion step
from the bulk solution toward the ZnFe2O4/NPs/IL/CPE
surface [29]. e average value of the diffusion coefficient
-1
1
3
5
7
9
11
13
15
0.40.5 0.60.7 0. 80.9
11
.1
Current (µA)
Potential (V) vs. Ag/AgCl
3
500
A
y = 0.0276x + 0.5508
R² = 0.9973
0
3
6
9
12
15
0100 200300 400500 600
Current (µA)
RC concentration (µM)
B
Fig. 8 A Square wave voltammetric curves for successive additions
of RC into PBS (0.1 M) pH 6 including RC concentrations of 3, 5, 10, 20,
30, 50, 100, 150, 200, 250, 300, 350, 400, and 500 µM on the surface of
ZnFe2O4/NPs/IL/CPE. B Typical calibration curve corresponding to RC
additions up to 500 µM
-0.5
0.5
1.5
2.5
3.5
4.5
00.2 0.40.6 0.81
Current (µA)
Potential (V) vs. Ag/AgCl
50.0 µ
µ
M (HQ) + 5.0 µ
µ
M(RC)
700.0 µ
µ
M(HQ) + 300.0 µ
µ
M(RC)
RC
HQ
A
y = 0.0021x -0.0869
R² =0.9919
-0.1
0.3
0.7
1.1
1.5
0150 300450 60
07
50
Current (µA)
HQ concentration (µM)
B
y = 0.0127x + 0.261
R² =0.9956
0
0.9
1.8
2.7
3.6
4.5
070140210 280350
Current (µA)
RC concentration (µM)
C
Fig. 9 A Square wave voltammetric curves for simultaneous
additions of HQ and RC into PBS (0.1 M) pH 6; from inner to outer
including HQ and RC concentrations of 50.0 + 5.0, 100.0 + 50.0,
200.0 + 100.0, 300.0 + 150.0, 400.0 + 200.0, 500.0 + 250.0, and
700.0 + 300.0 µM, respectively. B and C Typical calibration curves
corresponding to HQ and RC additions up to 700 and 300 µM,
respectively
Scheme1 Mechanism of RC electro-oxidation on the surface of
ZnFe2O4/NPs/IL/CPE
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
Page 10 of 12
Nabatianetal. BMC Chemistry (2022) 16:115
was found to be 2.83 × 10− 4 cm2s− 1 by substituting the
slopes of Cottrell plots and other parameters in the Cot-
trell equation.
Analytical performance characterization
e characteristics performance of the fabricated
ZnFe2O4/NPs/IL/CPE investigated with regard to several
operating parameters including linearity of the proposed
sensor response over the wide concentration range of
RC, limit of detection (LOD) and quantification (LOQ),
repeatability and reproducibility, lifetime and the effect
of interferences presence.
e square wave voltammetry (SWV) with lower back-
ground current compare to cyclic voltammetry adopted
for the determination of RC over a wide concentration
range in 0.1 M phosphate buffer solution (pH 6.0). As
seen from Fig.8, a linear relationship between oxidation
peaks current (Ip) and the concentration of RC over the
range from 3.0 µM to 500 µM with the satisfactory cor-
relation coefficient of 0.997 observed.
e observed deviation from the linear response at
higher concentration probably attributed to the dif-
fusion of RC or accumulation of the undesired oxida-
tion products on the surface of the proposed electrode.
e respective linear regression equations expressed as
below:
Ip (µA) = 0.0276 CRC (µM) + 0.5508 (R2 = 0.9973) (6).
e value of the limit of detection (LOD) for the pro-
posed electrode calculated according to the definition of
3Sb/m, where Sb as the standard deviation of peak cur-
rent derived from 10 measurements of the blank solu-
tion (Sb=1.348 × 10− 8) and m is the slope of the linear
calibration plot (m = 0.0276). e lower detection limit of
the proposed sensor was found to be 1.46 µM RC. Fur-
thermore, the value of the limit of quantification (LOQ)
according to the definition of 10Sb/m was found to be
4.88 µM RC by SWV employing ZnFe2O4/NPs/IL/CPE.
To evaluate the accuracy and precision of the fabricated
ZnFe2O4/NPs/IL/CPE, the repeatability and reproduc-
ibility of the proposed electrode assessed. e repeat-
ability investigated with five successive scans in one day
and five scans during five days using the same electrode.
e examined solutions contain 5.0 µM RC. e obtained
results revealed satisfactory repeatability with the relative
standard deviation of ± 1.33 and ± 2.70, respectively. On
the other hand, for reproducibility studies, five different
electrodes were used only once each and the obtained
results indicated good reproducibility of the proposed
sensor with the relative standard deviation of ± 3.41.
Moreover, to evaluate the stability of the response,
ZnFe2O4/NPs/IL/CPE immersed in an aqueous solution
and applied for the quantitative determination of RC
known concentrations in various samples. Assessment of
the obtained results indicated that the electrode revealed
stable response within 180 min and afterward the back-
ground current increased. e observed behavior is
possibly related to the leakage of 1-butyl-3-methylimida-
zolium tetrafluoroborate from the modified carbon paste
which increased the roughness of the fabricated elec-
trode. e obtained results showed that ZnFe2O4/NPs/
IL/CPE has acceptable repeatability and reproducibility
with a satisfactory stability.
Resorcinol andhydroquinone simultaneous
electrochemical determination
In order to provide a voltammetric approach for simul-
taneous determination of RC and HQ in pharmaceutical
products, SWV technique with high sensitivity and capa-
bility of oxidation peaks separation employed in the cur-
rent work. e SWVs plot recorded by the simultaneous
change of RC and HQ concentrations over a wide range
in 0.1 M phosphate buffer solution (pH 6.0). As seen in
Fig.9, two separate and highly intense oxidation peaks
at 290 mV and 650 mV related to HQ and RC achieved.
A satisfactory linear relationship between oxidation peak
current (Ip) and the concentration of HQ and RC over
the range of 50–700 µM and 5-350 µM with the favorable
correlation coefficient of 0.991 and 0.995, respectively,
observed.
It is apparent that at the surface of ZnFe2O4/NPs/IL/
CPE a desirable peak separation with the potential differ-
ence of about 360 mV (vs. Ag/AgCl reference electrode)
for HQ and RC obtained. e obtained results revealed
that the proposed electrode could be applied for the con-
current determination of RC and HQ in the presence of
each other without significant deviation in the electro-
chemical response.
Determination ofRC inthepresence ofcoexisting
interfering species
Further studies carried out to evaluate the ability of the
proposed sensor for discriminating between the desired
target of RC and the potential interfering species which
present in real samples such as pharmaceutical formula-
tions and biological fluids. Herein, the effect of interfer-
ing species including various kind of electrolytes, amino
acids, and sugar on the characteristic performance of
ZnFe2O4/NPs/IL/CPE investigated in the presence of
50 µM RC under the optimized experimental condition
(see Table1). It is noteworthy to mention that the toler-
ance limit of the proposed electrode defined as the maxi-
mum amount of interfering compounds which resulted
in a peak current deviation more than 5.0% for determi-
nation of RC compared to square wave voltammograms
of RC solution alone.
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
Page 11 of 12
Nabatianetal. BMC Chemistry (2022) 16:115
e obtained results revealed that the oxidation peak
current of RC deviated from the tolerance limit in the
presence of more than 500-fold excess of common elec-
trolytes including Ca2+, Mg2+, Na+, K+, SO42−, CO32−,
NO3−, and HCO3−. However, the presence of glucose
and ascorbic acid in the 500-fold and 200-fold excess
concentration had no interference with RC detection,
respectively. On the other hand, the oxidation peak cur-
rent of RC evaluated in the presence of 700-fold excess of
common amino-acids including phenylalanine, methio-
nine, alanine, valine, and isoleucine which used in the
biosynthesis of proteins. It found that the mention con-
centration did not show interference in the quantitative
determination of RC.
Lastly, the presence of some substances which need to
excrete from the body such as urea evaluated on the char-
acteristic performance of the proposed electrode. e
results showed that the ZnFe2O4/NPs/IL/CPE response
deviated from the tolerance limit in the presence of more
than 400-fold excess of urea and thiourea.
Analysis ofthepharmaceutical sample
In order to evaluate the performance of the fabricated
ZnFe2O4/NPs/IL/CPE for precise determination of RC in
the real samples, the resorcinol cream of 2% O/W emul-
sion available on the market studied. To prepare the real
sample of resorcinol cream for analysis, firstly, RC which
is a weakly acidic compound must be extracted from the
cream by the following method.
1 g of the cream carefully weighed and completely dis-
solved in 9 mL of distilled water. To extract the RC from
the obtained milky color diluted base, 2 g of NaCl salt
added for salting out process. Subsequently, the pH of
the obtained emulsion adjusted around 12.5 by adding
NaOH 0.1 M, which is 3 units higher than the pKa for
RC. Accordingly, the RC compound converted into the
ionized and hydrophilic form which could easily extract
from the lipophilic components of the obtained emulsion
and transferred into the aqueous phase. e obtained
mixture centrifuged for 20 min at 4000 rpm. 100 µL of the
supernatant phase transferred into the electrochemical
cell and diluted up to 10 mL by the phosphate buffer solu-
tion (0.1 M, pH 6.0). As seen from Table2, the commer-
cial resorcinol cream contains % 1.9 (w/w) resorcinol in
the O/W emulsion.
Analytical performance comparison oftheproposed
sensor withprevious works
e analytical performance of ZnFe2O4/NPs/IL/CPE for
simultaneous determination of RC and HQ compared
to the other reported sensors. As seen from Table 3,
the lower detection limit of the proposed electrode
was better than some reported graphene-based cases
[3, 4]. However, the carbon paste electrode in the cur-
rent work is much cheaper than the mention electrodes.
On the other hand, the present sensor revealed a wider
dynamic linear range compared to most of the summa-
rized reported sensors [3, 5, 6]. It can be concluded that
the present electrode is either comparable or superior
compared to the other reported sensors for simultaneous
determination RC and HQ.
Conclusion
e excellent electro-catalytic performance of RC and
HQ at the surface of ZnFe2O4/NPs/IL/CPE which was
not susceptible to common interferences provided a
new promising approach for simultaneous determina-
tion of trace amount of RC and HQ in pharmaceutical
samples using square wave voltammetry technique. e
SW voltammograms revealed two well-defined sepa-
rated oxidation peaks with a desirable peak separation
and a satisfactory linear response over a wide concen-
tration range of RC and HQ. e developed modified
carbon paste electrode showed a considerable improve-
ment in the kinetics of the electron transfer with an
excellent reproducible analytical performance which
indicated that the proposed sensor could be applied
successfully for routine analysis.
Acknowledgements
The authors express their appreciation to Kerman University of Medical Sci-
ences for supporting the current work (Grant No. 99001163).
Author contributions
SA conceived the original idea, supervised the project, and prepared the
manuscript. EN carried out the experiments. MP, MY and MM contributed
to the interpretation of the results and writing the manuscript. All authors
discussed the results and contributed to the final manuscript. All authors read
and approved the final manuscript.
Funding
Kerman University of Medical Sciences (Kerman, Iran) has provided financial
support for the project (Grant No. 99001163).
Availability of data and materials
Adequate and clear descriptions of the applied materials and tools are
provided in the materials and method section of manuscript. In addition, the
obtained data is clearly justified by mentioning the figures and tables in the
manuscript.
Declarations
Ethics approval and consent to participate
The current work was conducted in the autumn of 2021, after receiving
approval from the ethics committee of Kerman University of Medical Sciences
[IR.KMU.REC.1399.673].
Consent for publication
Not applicable.
Competing interests
The authors have declared no competing interest.
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
Page 12 of 12
Nabatianetal. BMC Chemistry (2022) 16:115
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Author details
1 Student Research Committee, Kerman University of Medical Sciences, Ker-
man, Iran. 2 Department of Chemistr y, Faculty of Sciences, Shahid Bahonar
University of Kerman, Kerman, Iran. 3 Department of Medicinal Chemistry,
Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran.
4 Department of Chemistry, Faculty of Chemistry and Chemical Engineering,
Graduate University of Advanced Technology, Kerman, Iran. 5 Pharmaceutics
Research Center, Institute of Neuropharmacology, Kerman University of Medi-
cal Sciences, Kerman, Iran. 6 Pharmaceutical Sciences and Cosmetic Products
Research Center, Kerman University of Medical Sciences, Kerman, Iran.
Received: 6 August 2022 Accepted: 24 November 2022
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