Colloids and Surfaces B: Biointerfaces 85 (2011) 289–292

Contents lists available at ScienceDirect

Colloids and Surfaces B: Biointerfaces

journal homepage: www.elsevier.com/locate/colsurfb

Electrochemical behavior and voltammetric determination of paracetamol on

Nafion/TiO2 –graphene modified glassy carbon electrode
Yang Fan ∗ , Jin-Hang Liu, Hai-Ting Lu, Qin Zhang
College of Chemistry and Chemical Engineering, Xinyang Normal University, Xinyang 464000, PR China

a r t i c l e i n f o a b s t r a c t

Article history: The TiO2 –graphene (TiO2 –GR) nanocomposite for paracetamol electrochemical sensing is described. The
Received 14 January 2011 electrochemical behavior of paracetamol at the Nafion/TiO2 –GR composite film modified glassy carbon
Received in revised form 19 February 2011 electrode (GCE) was investigated by cyclic voltammetry. The results showed that the incorporation of
Accepted 25 February 2011
TiO2 nanoparticles with graphene significantly enhanced the electrochemical reactivity and voltammetric
Available online 8 March 2011
response of paracetamol. In addition, Nafion acts as an effective solubilizing agent and antifouling coating
in the fabrication of the modified electrode. This electrochemical sensor exhibits excellent analytical
Keywords:
performance for paracetamol detection at physiological pH with detection limit of 2.1 × 10−7 M, linear
Paracetamol
Graphene
range of 1–100 ␮M and reproducibility of 3.6% relative standard deviation.
TiO2 –graphene nanocomposite © 2011 Elsevier B.V. All rights reserved.
Electrochemical sensor

1. Introduction trode surface, paracetamol only exhibits sluggish voltammetric

Paracetamol (acetaminophen, N-acetyl-p-aminophenol) is
widely used as an antipyretic and analgesic drug. It is an effective
and safe analgesic agent used for the relief of mild to mod-
erate pain associated with headache, backache, arthritis and
postoperative pain [1]. It is also used for reduction of fevers of
viral and bacterial origin. Paracetamol relieves pain and fever
by inhibiting prostaglandin’s synthesis in the central nervous
system and sedating hypothalamic heat-regulating center [2]. As
a weak acid with pKa of 9.5, paracetamol rapidly gets absorbed
and distributed after oral administration and is easily excreted
in urine [3]. Generally, paracetamol does not exhibit any harmful
side effects. However, hypersensitivity or overdoses of parac-
etamol leads to the formation of some liver and nephrotoxic
metabolites. Moreover, the hydrolytic degradation product of
paracetamol is 4-aminophenol which can cause teratogenic effect
and nephrotoxicity. This species can be found in pharmaceutical
preparations as a degradation product of paracetamol or as a
synthetic intermediate [4]. Thus, the development of simple,
sensitive and accurate analytical methods for determination of
paracetamol in pharmaceutical preparations and human plasma
is of great importance. To date, electrochemical techniques have
been widely explored for paracetamol detection, which have
the advantages of high sensitivity, less time-consuming and low
costs over other analytical methods. However, at traditional elec-
∗ Corresponding author. Tel.: +86 376 6391825; fax: +86 376 6391825.
E-mail address: yfanchem@gmail.com (Y. Fan).
response. Thus, considerable efforts have been devoted to develop
chemically modified electrodes to enhance the voltammetric
response and analytical performance for paracetamol detection
[5–16].
Graphene-based electrochemical sensors have recently exhib-
ited excellent analytical performance for small biomolecules
detection [17–20]. Owing to its extraordinary electronic trans-
port properties and high electrocatalytic activities, graphene
greatly promotes the electrochemical reactivity of biomolecules
on the modified electrode surface. Furthermore, the unique two-
dimensional crystal structure of graphene makes it extremely
attractive as a support material for metal and metal-oxide
catalyst nanoparticles [21]. These graphene-based hybrid mate-
rials have shown greater versatility as enhanced materials for
electrochemical sensors application [22–28]. Most recently, we
developed an effective hydrothermal method for the preparation
of TiO2 –graphene (TiO2 –GR) nanocomposite [29]. Owing to its high
adsorptivity and good biocompatibility, the incorporation of TiO2
nanoparticles with graphene significantly promotes the electro-
chemical sensing performance for dopamine detection.
In this paper, we prepared the Nafion/TiO2 –GR composite film
modified glassy carbon electrode (GCE) for electrochemical sens-
ing of paracetamol. Nafion, the widely used perfluorosulfonated
polymer, acts as an effective solubilizing agent for the TiO2 –GR
nanocomposite, as well as an antifouling coating to reduce the
interference of the surface-active macromolecules. The electro-
chemical behavior of paracetamol on the Nafion/TiO2 –GR film was
investigated in detail. This electrochemical sensing interface exhib-
ited excellent performance towards paracetamol detection, which

0927-7765/$ – see front matter © 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.colsurfb.2011.02.041
290 Y. Fan et al. / Colloids and Surfaces B: Biointerfaces 85 (2011) 289–292
established an effective sensing and screening platform for certain
pharmaceutical preparations.
2. Experimental
2.1. Apparatus and reagents
Paracetamol, ascorbic acid (AA) and dopamine (DA) and N,N-
dimethylformamide (DMF) were obtained from Aladdin Chemistry
Co., Ltd. Nafion (5 wt.% in lower aliphatic alcohols and water) was
purchased from Sigma–Aldrich. All other chemicals were of analyt-
ical reagent grade and used as received. Water used throughout all
experiments was purified with the Millipore system.
All electrochemical experiments were performed with a CHI
850 C electrochemical workstation (CH Instruments, Shanghai,
China). A conventional three-electrode system was used for all
electrochemical experiments, which consisted of a platinum wire
as counter electrode, an Ag/AgCl/3 M KCl as reference electrode,
and a bare or modified glassy carbon electrode (3 mm diameter) as
working electrode.
2.2. Preparation of modified electrode
The as-prepared TiO2 –GR nanocomposite [29] was dispersed in
DMF containing 2.5% (V/V) Nafion with ultrasonication for 1 h to get
a homogenous suspension (1 mg mL−1 ). Then, 5 ␮L of the suspen-
sion was dropped onto the surface of freshly polished glassy carbon
electrode (GCE) and dried at room temperature, resulting in the
Nafion/TiO2 –GR modified GCE (Nafion/TiO2 –GR/GCE). For compar-
ison, 5 ␮L of the homogenous suspension (1 mg mL−1 ) of graphene
in DMF containing 2.5% (V/V) Nafion was coated on bare GCE to
obtain the Nafion/GR modified GCE (Nafion/GR/GCE).
3. Results and discussion
3.1. Electrochemical behavior of paracetamol on
Nafion/TiO2 –GR/GCE
Fig. 1 depicts the cyclic voltammograms (CVs) of paraceta-
mol on the bare GCE, Nafion/GR/GCE and Nafion/TiO2 –GR/GCE
in 0.1 M PBS (pH 7.0), respectively. On the bare GCE (Fig. 1a),
paracetamol shows an irreversible redox behavior with small and
undefined redox peaks. In contrast, on the Nafion/GR/GCE (Fig. 1b),
the anodic and cathodic peak currents are significantly increased
-60
-40
c
b -100
-20
Current / A
a
0 0
20
40
0.0 0.2 0.4 0.6 0.8 1.0
Potential / V vs. Ag/AgCl
Fig. 1. CVs of 1.0 mM paracetamol on the (a) bare GCE, (b) Nafion/GR/GCE and (c)
Nafion/TiO2 –GR/GCE in 0.1 M PBS (pH 7.0), at scan rate of 50 mV s−1 .
with peak potentials located at 0.575 and 0.510 V, respectively. The
remarkably enhanced voltammetric response of paracetamol on
the Nafion/GR/GCE can be reasonably ascribed to the large spe-
cific surface area and electrocatalytic activity of graphene, which
improves the absorption efficiency and electrochemical reactiv-
ity of paracetamol [5]. In the case of Nafion/TiO2 –GR/GCE, a pair
of well-defined and quasi-reversible redox peaks corresponding
to the electrochemical reaction of paracetamol was obtained,
with Epa = 0.510 V and Epc = 0.465 V. It can be seen that the oxi-
dation overpotential of paracetamol becomes lower than that
on Nafion/GR/GCE with a negative shifting of 65 mV. Moreover,
oxidation peak current significantly increases to 44.8 ␮A, which
is 1.9 times higher than that on Nafion/GR/GCE. These results
demonstrated that the electrochemical reactivity of paracetamol is
remarkably improved on the Nafion/TiO2 –GR composite film. It is
suggested that, owing to its high adsorptivity and good biocompat-
ibility [6,30–33], TiO2 nanoparticles effectively modify the surface
chemistry of graphene sheets, which provides an efficient interface
and microenvironment for the electrochemical reaction of parac-
etamol. In addition, it was observed that Nafion can be used as an
effective solubilizing agent for the TiO2 –GR nanocomposite to form
a well-dispersed suspension, as well as an antifouling coating to
reduce the interference of the surface-active macromolecules [34].
3.2. The redox mechanism of paracetamol on
Nafion/TiO2 –GR/GCE
The effect of scan rate on the anodic and cathodic peak
current of paracetamol on the Nafion/TiO2 –GR/GCE was inves-
tigated. As shown in Fig. 2, the anodic and cathodic peak
currents increase linearly as the scan rate grows from 50 to
300 mV s−1 . The linear relationship between the peak current
and the scan rate was obtained with the linear regression
equation as: Ipa /␮A = −40.79–0.5785 v/mV s−1 (R = 0.9933) and
Ipa /␮A = 32.04 + 0.3529 v/mV s−1 (R = 0.9948), respectively. This
result indicates that the electrochemical reaction of paraceta-
mol on the Nafion/TiO2 –GR film is a surface-controlled process.
At high scan rates ranging from 100 to 300 mV s−1 , plotting
the Epa and Epc vs. logv produces a straight line with the lin-
ear regression equations as: Epa = 0.6134 + 0.0853logv (R = 0.9913)
and Epc = 0.3647–0.05011logv (R = 0.9980), respectively. According
to Laviron’s equation [35], the slops of the lines are equal to
2.3RT/(1 − ˛)nF and −2.3RT/˛nF, respectively. Therefore, the elec-
-300
100 300 mV s -1
Peak current / µA
0
-200
50 mV s -1
-100
Current / µA
-200
50 100 150 200 250 300
Potential / V vs. Ag/AgCl
100
0.0 0.2 0.4 0.6 0.8
Potential / V vs. Ag/AgCl
Fig. 2. CVs of 1.0 mM paracetamol on Nafion/TiO2 –GR/GCE at different scan rates
(50, 100, 150, 200, 250 and 300 mV s−1 ) in 0.1 M PBS (pH 7.0). Insert, the plot of the
peak current vs. scan rate.
 Y. Fan et al. / Colloids and Surfaces B: Biointerfaces 85 (2011) 289–292 291

-80
0.7 -40

E0' / V vs. Ag/AgCl

30

pH

Peak current / A
0.6
-60 4
8 20

-30
10
-40 0.5

Current / µA
Current / µA

4 5 6 7 8 0 20 40 60 80 100
-20 pH -20 Concentration / µA

-10
20

40 0.3 0.4 0.5 0.6

-0.2 0.0 0.2 0.4 0.6 0.8 1.0
Potential / V vs. Ag/AgCl
Potential / V vs. Ag/AgCl
Fig. 4. DPVs of 1.0, 2.0, 4.0, 6.0, 8.0, 10, 20, 40, 60, 80 and 100 ␮M paracetamol
Fig. 3. CVs of 1.0 mM paracetamol on Nafion/TiO2 –GR/GCE in 0.1 M PBS with pH on Nafion/TiO2 –GR/GCE in 0.1 M PBS (pH 7.0). Insert, the plot of peak current vs.
values of 4.0, 5.0, 6.0, 7.0 and 8.0. Insert, the plot of formal potential vs. pH value. paracetamol concentration.
Scan rate: 50 mV s−1 .

tron transfer coefficient (˛) and the electron transfer number (n) are
calculated to be 0.63 and 1.9, respectively. The adsorbed amount
of paracetamol on the surface of Nafion/TiO2 –GR/GCE was fur-
ther calculated by the following equation: ip = n2 F2 A v/4RT [35].
Based on the relationship of ip with v, the value of the sur-
face concentration of the paracetamol ( ) was obtained with
the results as 3.24 × 10−9 mol cm−2 , which is higher than that
(3.7 × 10−10 mol cm−2 ) at the PAY/nano-TiO2 /GCE [6], indicating
increased adsorptivity of the Nafion/TiO2 –GR composite film.
The effect of pH on the redox reaction of paracetamol at
the Nafion/TiO2 –GR/GCE was investigated in the range of pH
4.0–8.0. As shown in Fig. 3, the redox peak shifted negatively with
increasing solution pH, indicating that proton is involved in the
redox reaction of paracetamol. A good linear relationship can be

established between the formal potential (E0 ) and solution pH
with the linear regression equation as: Ep /V = 0.8592–0.04860pH
(R = 0.9940). Based on the equation dEp /dpH = 0.059/˛n, the
proton number () was estimated to be 1. Thus, the electro-
chemical reaction of paracetamol on the Nafion/TiO2 –GR film is a
one-proton and two-electron process, which is in agreement with
the literature reports [5,8].
3.3. Voltammetric determination of paracetamol
The voltammetric determination of paracetamol was carried
out in 0.1 M PBS (pH 7.0) using differential pulse voltammetry
at the Nafion/TiO2 –GR/GCE. Fig. 4 depicts the differential pulse
voltammograms (DPVs) of various concentrations of paraceta-
mol. The peak current increases linearly against the concentration
of paracetamol within the range of 1–100 ␮M. The calibration
curve for paracetamol shows two linear segments: the first lin-
ear segment increases from 1 to 20 ␮M with the linear regression
equation of Ipa /␮A = −0.02412–0.1649cparacetamol /␮M (R = 0.9962),
and the second linear segment increases up to 100 ␮M with the
linear regression equation of Ipa /␮A = 4.049–0.3472cparacetamol /␮M
(R = 0.9968). The first linear region in the calibration curve can be
ascribed to an absorption process of paracetamol to form a sub-
monolayer, and the second linear region was a process for the
formation of a monolayer-covered surface [7]. The detection limit
(S/N = 3) was estimated to be 2.1 × 10−7 M. The detection limit, lin-
ear range and solution pH used for detection of paracetamol were
compared with the earlier reports in Table 1. It can be seen that this
new method could be applied for paracetamol detection in neutral
buffer solution (pH 7.0) with low detection limit and wide linear
range.
The long-term stability of the Nafion/TiO2 –GR/GCE electro-
chemical sensor was investigated by examining its current
response during storage in a refrigerator at 4 ◦ C. The electrochem-
ical sensor exhibited no obvious decrease in current response
in the first week and maintained about 93% of its initial value
after two weeks. The relative standard deviation (RSD) of the
Nafion/TiO2 –GR/GCE in response to 50 ␮M paracetamol for ten
measurements was 3.6%, indicating the good reproducibility.
In biological samples, paracetamol generally suffers from the
interferences of ascorbic acid (AA) and dopamine (DA). Thus, exper-
iment with interferences including AA and DA was performed to
test the selectivity of the Nafion/TiO2 –GR sensing platform. As
shown in Fig. 5, paracetamol exhibits well-defined DPV wave with
good separations from AA and DA. Therefore, it could be possible
for selective detection of paracetamol in the presence of AA and DA.
The developed method was applied to the analysis of a kind of
paracetamol (500 mg/tablet) commercial tablet. The tablets were
ground to powder and dissolved in 0.1 M PBS (pH 7.0). Using
this method, the concentration of paracetamol was detected to be
493 mg/tablet, which is in good agreement with content of parac-
etamol provided by the manufacture.

Table 1
Comparison of the performances of some paracetamol electrochemical sensors.

Modified electrodes pH used Detection limit (M) Linear range (␮M) References

Graphene/GCE 9.3 3.2 × 10−8 0.1–20 [5]

PAY/nano-TiO2 /GCE 7.0 2.0 × 10−6 12–120 [6]
MWCNT-BPPGE 7.5 1.0 × 10−8 0.01–20 [7]
C60 /GCE 7.2 0.5 × 10−4 50–1500 [8]
PANI-MWCNTs/GCE 5.5 2.5 × 10−7 1–100 [9]
C–Ni/GCE 3.0 6.0 × 10−7 2–230 [10]
Nafion/TiO2 –graphene/GCE 7.0 2.1 × 10−7 1–100 This work
292 Y. Fan et al. / Colloids and Surfaces B: Biointerfaces 85 (2011) 289–292

-30 References

paracetamol [1] R.M.D. Carvalho, R.S. Freire, S. Rath, L.T. Kubota, J. Pharm. Biomed. Anal. 34
(2004) 871.
[2] Martindale, The Extra Pharmacopoeia, 29th ed., The Pharmaceutical Press, Lon-
don, 1989, p. 32.
[3] J. Parojčić, K. Karljiković-Rajić, Z. Ðurić, M. Jovanović, S. Ibrić, Biopharm. Drug
Current /µA

-20 Dispos. 24 (2003) 309.

AA
DA
-10
0.2 0.4 0.6
Potential / V vs. Ag/AgCl
Fig. 5. DPVs recorded on Nafion/TiO2 –GR/GCE with AA (0.2 mM), DA (0.2 mM) and
paracetamol (0.4 mM) in 0.1 M PBS (pH 7.0).
4. Conclusions
In summary, we have studied the electrochemical behavior of
paracetamol on the Nafion/TiO2 –GR composite film modified elec-
trode. The results indicate that the Nafion/TiO2 –GR nanocomposite
can provide a favorable interface and microenvironment for the
electrochemical reaction of paracetamol. The composite film mod-
ified electrode was successfully employed for the voltammetric
determination of paracetamol with low detection limit, wide linear
range and good selectivity. We also demonstrated the application
of Nafion/TiO2 –GR/GCE for paracetamol detection in commercial
tablets with satisfactory results.
Acknowledgements
This work was financially supported by the National Natural Sci-
ence Foundation of China (No. 21002082) and the Key Project of
Chinese Ministry of Education (No. 210129).
[4] A. Yesilada, H. Erdogan, M. Ertan, Anal. Lett. 24 (1991) 129.
[5] X. Kang, J. Wang, H. Wu, J. Liu, I.A. Aksay, Y. Lin, Talanta 81 (2010) 754.
[6] S.A. Kumar, C.F. Tang, S.M. Chen, Talanta 76 (2008) 997.
[7] R.T. Kachoosangi, G.G. Wildgoose, R.G. Compton, Anal. Chim. Acta 618 (2008)
54.
[8] R.N. Goyal, S.P. Singh, Electrochim. Acta 51 (2006) 3008.
[9] M. Li, L. Jing, Electrochim. Acta 52 (2007) 3250.
[10] S.F. Wang, F. Xie, R.F. Hu, Sens. Actuators B 123 (2007) 495.
[11] M. Boopathi, M.S. Won, Y.B. Shim, Anal. Chim. Acta 512 (2004) 191.
[12] B.C. Lourencão, R.A. Medeiros, R.C. Rocha-Filho, L.H. Mazoa, O. Fatibello-Filho,
Talanta 78 (2009) 748.
[13] N.F. Atta, M.F. El-Kady, A. Galal, Sens. Actuators B 141 (2009) 566.
0.8 [14] D. Nematollahia, H. Shayani-Jama, M. Alimoradib, S. Niroomandb, Electrochim.
Acta 54 (2009) 7407.
[15] P. Fanjul-Bolado, P.J. Lamas-Ardisana, D. Hernández-Santos, A. Costa-García,
Anal. Chim. Acta 638 (2009) 133.
[16] A. Özcan, Y. Sahin, Anal. Chim. Acta 685 (2011) 9.
[17] Y. Shao, J. Wang, H. Wu, J. Liu, I.A. Aksay, Y. Lin, Electroanalysis 22 (2010) 1027.
[18] M. Pumera, A. Ambrosi, A. Bonanni, E.L.K. Chng, H.L. Poh, Trends Anal. Chem.
29 (2010) 954.
[19] D. Chen, L. Tang, J. Li, Chem. Soc. Rev. 39 (2010) 3157.
[20] M. Zhou, Y. Zhai, S. Dong, Anal. Chem. 81 (2009) 5063.
[21] P.V. Kamat, J. Phys. Chem. Lett. 1 (2010) 520.
[22] S. Guo, D. Wen, Y. Zhai, S. Dong, E. Wang, ACS Nano 4 (2010) 3959.
[23] C. Shan, H. Yang, D. Hana, Q. Zhang, A. Ivaska, L. Niu, Biosens. Bioelectron. 25
(2010) 1070.
[24] E. Jin, X. Lu, L. Cui, D. Chao, C. Wang, Electrochim. Acta 55 (2010) 7230.
[25] W. Hong, H. Bai, Y. Xu, Z. Yao, Z. Gu, G. Shi, J. Phys. Chem. C 114 (2010) 1822.
[26] L. Li, Z. Du, S. Liu, Q. Hao, Y. Wang, Q. Li, T. Wang, Talanta 82 (2010) 1637.
[27] H. Wu, J. Wang, X. Kang, C. Wang, D. Wang, J. Liu, I.A. Aksay, Y. Lin, Talanta 80
(2009) 403.
[28] H. Yin, Y. Zhou, Q. Ma, S. Ai, Q. Chen, L. Zhu, Talanta 82 (2010) 1193.
[29] Y. Fan, H.T. Lu, J.H. Liu, C.P. Yang, Q.S. Jing, Y.X. Zhang, X.K. Yang, K.J. Huang,
Colloids Surf. B 83 (2011) 78.
[30] H. Lin, X. Ji, Q. Chen, Y. Zhou, C.E. Banks, K. Wu, Electrochem. Commun. 11
(2009) 1990.
[31] Y. Luo, H. Liu, Q. Rui, Y. Tian, Anal. Chem. 81 (2009) 3035.
[32] X. Xie, K. Yang, D. Sun, Colloids Surf. B 67 (2008) 261.
[33] S.J. Bao, C.M. Li, J.F. Zang, X.Q. Cui, Y. Qiao, J. Guo, Adv. Funct. Mater. 18 (2008)
591.
[34] J. Wang, M. Musameh, Y. Lin, J. Am. Chem. Soc. 125 (2003) 2408.
[35] E. Laviron, J. Electroanal. Chem. 101 (1979) 19.