Electrochemistry Communications 7 (2005) 803–807

www.elsevier.com/locate/elecom

Differential pulse voltammetric determination of paracetamol

at nanogold modified indium tin oxide electrode
a,*
Rajendra N. Goyal , Vinod K. Gupta a, Munetaka Oyama b, Neeta Bachheti a

a
Department of Chemistry, Indian Institute of Technology Roorkee, Roorkee-247 667, India
b
Division of Research Initiatives, International Innovation Center, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan

Received 20 April 2005; received in revised form 11 May 2005; accepted 11 May 2005
Available online 13 June 2005

Abstract

A nanogold modified indium tin oxide (ITO) electrode was used for the determination of paracetamol at pH 7.2. The electrode
exhibited an effective catalytic response to the oxidation of paracetamol with good reproducibility and stability. Under conditions
of differential pulse voltammetry, the oxidation potential of paracetamol is lowered by approximately 110 mV and current response
is enhanced significantly relative to the situation prevailing when a bare ITO electrode is used. Linear calibration curve is obtained over
the range 2.0 · 10
7–1.5 · 10
3 M with a correlation coefficient of 0.997. The detection limit (3r) was estimated to be 1.8 · 10
7 M. The
physiologically common interferents viz., ascorbic acid, glucose and urea negligibly affected the current response of paracetamol. The
practical analytical utility of the method is illustrated by determination of paracetamol in pharmaceutical preparations.

2005 Elsevier B.V. All rights reserved.

Keywords: Nanogold modified indium tin oxide electrode; Paracetamol; Differential pulse voltammetry; Pharmaceutical preparations

1. Introduction ache, joint pain, general pain and toothache [2–4]. It is

Paracetamol (I, N-acetyl-p-aminophenol, acetamino-
phen) is a long-established and one of the most extensively
employed ‘‘over the counter’’ drugs in the world. It was
first used in medicine by Von Mering in 1893. However,
it was first discovered to have both analgesic and antipy-
retic properties in the late 19th century. It is noncarcino-
genic and an effective substitute to aspirin for patients
with sensitivity to aspirin [1]. Unlike aspirin, however, par-
acetamolÕs anti-inflammatory activity is considered weak
and is, thus, not routinely used in inflammatory conditions
such as rheumatoid arthritis. Nevertheless, it is used to re-
duce fever cough and cold, and reduce mild to moderate
pain, including instances of tension headache, migraine
headache, muscular aches, chronic pain, neuralgia, back-
*
Corresponding author. Tel.: +91 1332 285794; fax: +91 1332
273560.
E-mail address: rngcyfcy@iitr.ernet.in (R.N. Goyal).
also useful in osteoarthritis therapy [5] and it is sometimes
used for management of cancer pain. Recent research sug-
gests that paracetamol may help to protect from changes
leading to hardening of arteries that cause cardiovascular
disease [6]. It also remains the analgesic of choice for peo-
ple with asthma [7]. There is also some evidence to suggest
that paracetamol may offer some protection against ovar-
ian cancer [8]. Paracetamol shows no propensity to be
addictive, even in people who use it frequently. When used
in proper therapeutic dose, paracetamol is readily metab-
olized. Overdoses of paracetamol produce toxic metabo-
lite accumulation that causes acute hepatic necrosis,
inducing morbidity and mortality in humans [9]. Thus, it
is very important to have an analytical technique for the
determination of paracetamol in pharmaceutical
preparations.
Several analytical techniques such as titrimetry
[10], spectrophotometry [11], spectrofluorometry [12],
voltammetry [13], HPLC [14], TLC [15], colorimetry

1388-2481/$ - see front matter
2005 Elsevier B.V. All rights reserved.
doi:10.1016/j.elecom.2005.05.005
804 R.N. Goyal et al. / Electrochemistry Communications 7 (2005) 803–807
[16], Fourier transform infra red spectrometry [17], and
many other methods are proposed for the determination
of paracetamol. Since voltammetric techniques are more
selective, less costly and less time-consuming, they are
widely used for the determination of paracetamol in phar-
maceutical preparations. Shuyan et al. described a rela-
tively simple and rapid electrochemical method by cyclic
voltammetry using glassy carbon electrode for the detec-
tion of paracetamol in 1.0 M HCl solution [18]. Voltam-
metric determination of paracetamol at chemically
modified electrodes [19,20], boron doped diamond film
electrode [21] and at other electrodes [22–25] have also at-
tracted attention, however, the lowest detection limit of
1.2 lM is reported at nafion/ruthenium oxide pyrochlore
chemically modified electrode.
Owing to their novel optical, electronic, magnetic and
catalytic properties gold nanoparticles are one of the
most intensively studied and one of the most popular
materials to be assembled on electrodes [26]. It has been
reported that the small size of gold nanoparticles allow
the conductive materials to come into the vicinity of
the active process providing bioelectrocatalytic activity
that can be utilized in the construction of biosensors
[27]. It also provides some important functions for elec-
troanalysis [28]. Gold nanoparticles-modified electrodes
are used increasingly in many electrochemical applica-
tions since they have the ability to enhance the electrode
conductivity and facilitate the electron transfer, thus,
improving the analytical selectivity and sensitivity. Nor-
mally peculiar binding molecules are used to assemble
gold nanoparticles on the electrode surfaces [29,30] but
this may alter the conducting properties of the modified
electrode [31]. Recently, Oyama et al. [32] have pre-
sented a new method to fabricate a gold nanoparticles-
attached indium tin oxide (Au/ITO) electrode without
using peculiar binding molecules. The present work re-
ports the differential pulse voltammetric determination
of paracetamol at a physiological pH of 7.2 using gold
nanoparticles-modified indium tin oxide (Au/ITO) elec-
trode. The modified electrode shows a strong catalytic
function towards the oxidation of paracetamol. A detec-
tion limit of 0.18 lM is attained which is lower than that
of other electrochemical methods reported.
2. Experimental
2.1. Reagents
Paracetamol was received as a gift from Sri Krishna
Pharmaceuticals Ltd. (India) and was used as received.
Ascorbic acid, glucose and urea were obtained from
Merck. All other reagents used were of analytical grade.
All solutions were prepared in double distilled water.
Phosphate buffer solutions (l = 1 M) at various pH val-
ues, prepared according to the method of Christian and
Purdy [33], were used as supporting electrolyte for the
determination of paracetamol.
2.2. Apparatus and procedure
Differential pulse voltammetric experiments were per-
formed on BAS (Bioanalytical Systems, West Lafayette,
IN, USA) CV-50W Voltammetric analyzer. The electro-
chemical measurements were carried out in a single-
compartment three-electrode glass cell with a gold
nanoparticles modified ITO electrode (geometric area
ca. 0.0314 cm2) as the working electrode, a platinum wire
as counter electrode and Ag/AgCl electrode as reference
electrode (Model MF-2052 RB-5B). Gold nanoparticles
modified ITO electrodes were prepared by the method re-
ported in the literature [32]. JEOL JSM-7400F field emis-
sion scanning electron microscopy (FE-SEM) instrument
was used to characterize the growth of the gold nanopar-
ticles on the ITO surface. All experiments were carried
out at an ambient temperature of 25 ± 2 C. Stock solu-
tion of paracetamol (2 mM) was prepared by dissolving
the required amount of the compound in double distilled
water. The solution was wrapped with black paper and
kept in the dark. Freshly prepared solutions of paraceta-
mol were prepared each day owing to its low stability. To
record differential pulse voltammograms (DPVs), the
following instrumental parameters were used: pulse
amplitude, 5 mV; sample width, 2 ms; pulse width, 5 ms;
pulse period, 200 ms; scan rate, 20 mV/s; sensitivity,
100 nA/V.
3. Results and discussion
3.1. Electrochemical behavior of paracetamol
The typical surface image of gold nanoparticles mod-
ified ITO electrode, observed using a field-emission type
scanning electron microscopy (FE-SEM), is shown in
Fig. 1. On the surface of the ITO crystals, it is recognized
that gold nanospheres and nanorods were attached and
 R.N. Goyal et al. / Electrochemistry Communications 7 (2005) 803–807 805

Fig. 3. A calibration plot observed for paracetamol at nanogold

modified ITO electrode at pH 7.2.

Fig. 1. A typical FESEM image of nanogold modified ITO electrode.

The calibration curve for the DPV peak current for
paracetamol oxidation vs. paracetamol concentration
(Fig. 3) shows excellent linearity over a wide concentra-
tion range of 0.2 lM to 1.5 mM at pH 7.2 with a corre-
lation coefficient of 0.997 and can be expressed by the
equation:
ip ðnAÞ ¼ 0.0107C; where C is in lM=L.
The detection limit (3r) of paracetamol is
1.8 · 10
7 M. The linear behavior of the calibration
curve further indicates that the process is basically diffu-
sion controlled within the studied concentration range.
The percentage error in the calculated detection limit
was estimated to be 1.0%.
Modification of indium tin oxide surface by gold
nanoparticles remarkably improves the reactivity of
ITO electrode towards the oxidation of paracetamol,
thus, making it possible to detect paracetamol in a solu-
tion upto as low as 0.2 lM.

Fig. 2. A typical differential pulse voltammogram for 1.0 mM para- 3.2. Effect of pH
cetamol at pH 7.2 at bare (- - -) and gold nanoparticles modified (—)
ITO electrode.
The pH of the solution has a significant influence on
the peak potential of the catalytic oxidation of paracet-
effectively modified. The catalytic function of the gold amol. Fig. 4 illustrates the dependence of the DPV peak
nanoparticles modified ITO electrode is demonstrated
in Fig. 2 for 1.0 mM paracetamol at pH 7.2 recorded at
a bare ITO electrode and the nanogold particles modified
electrode by DPV. Paracetamol gives a peak response at
about 940 mV vs. Ag/AgCl at the bare ITO electrode,
while the use of gold nanoparticles modified ITO elec-
trode leads to an anodic peak at about 830 mV vs. Ag/
AgCl and the peak current increased greatly. The en-
hanced peak current response is a clear evidence of the
catalytic effect of the gold nanoparticles modified ITO
electrode towards oxidation of paracetamol. Also, a shift
in the oxidation potential of paracetamol by about
110 mV in the cathodic direction was observed at the
modified electrode. The lowering of peak potential is,
again, a good indication of the catalytic effect. Fig. 4. Observed dependence of Ep on pH for 0.1 mM paracetamol.
806 R.N. Goyal et al. / Electrochemistry Communications 7 (2005) 803–807

potential of paracetamol on the pH. As can be seen, the Table 2

peak potential for paracetamol oxidation varies linearly Influence of potential interferents on the voltammetric response of
0.10 mM paracetamol at the gold nanoparticles modified ITO
with pH and is shifted to more negative potentials with electrode
increase in pH. The dependence of Ep on pH at gold
Interferent Concentration of Change in current
nanoparticles modified ITO electrode can be expressed interferents (mM) responsea for 0.10 mM
by the relation paracetamol (nA)
Ep ðpH 3.0–11.04Þ ¼ ½1109.7–36.33 pH Ascorbic acid 0.05 0.060
0.50 0.204
in mV vs. Ag/AgCl having correlation coefficient of 1.00 0.201
approximately 0.983.
Glucose 0.05
0.091
As paracetamol oxidation is known to involve two 0.50 0.181
protons and two electrons, the slope would be expected 1.00 0.152
to be 59 mV pH
1. The 36 mV pH
1 slope obtained in Urea 0.05
0.012
the present studies indicates that the electrode process 0.50 0.152
is more complex. 1.00 0.204
a
The current in absence of any interferent was 1.17 nA.
3.3. Recovery test of paracetamol
3.5. Reproducibility of the modified electrode
The recovery tests of paracetamol ranging from
2.0 · 10
7 to 5.0 · 10
5 M were performed using DPV.
The reproducibility of the gold nanoparticles modi-
The results are listed in Table 1. The recoveries lie in
fied ITO electrode was investigated. The peak current
the range from 96.5% to 102.0%. The relative standard
response of 0.10 mM paracetamol was determined
deviation was 2.25%.
repeatedly with the same electrode for six times. It
showed a relative standard deviation of 2.4% confirming
3.4. Effect of interferents
that the results are reproducible.
The specificity of gold nanoparticles modified ITO
electrode to paracetamol in the presence of some pos- 3.6. Analysis of commercial samples
sible interfering substances like ascorbic acid, glucose
and urea was examined for their influence on the vol- The developed method was applied to the analysis of
tammetric response of paracetamol. DPV experiments four different commercial tablets viz. Calpol (Burroughs
were carried out for 0.10 mM paracetamol in the pres- Wellcome [India] Ltd., Batch No. W4025), Crocin
ence of 0.05–1.00 mM of each of the interferents. The (Glaxo Smithkline Asia Pvt. Ltd., Batch No. Y4045),
results are compiled in Table 2. In all cases, there was Paracetamol (Vapi Care Pharma P. Ltd., Batch No.
no substantial change in current response for 0.10 mM VCP402) and Paracip (Cadila Ltd., Batch No.
paracetamol in the presence of less than five fold ex- DA4122) each containing 500 mg of paracetamol and
cess of interferents. At higher concentrations of these of 125 mg 5 ml
1 pyrigesic syrup (East India Pharmaceu-
interferents the variation was within ±0.204 nA relative tical Works limited, Batch No. ES4006). The tablets were
to that in their absence. Thus, the response of paracet- grounded to powder and then dissolved in water. All the
amol at the gold nanoparticles modified ITO electrode samples were further diluted with water in order that the
is not affected by the interferents examined here below concentration of paracetamol was in the working range.
five fold concentrations. Following the proposed method, the concentration of
paracetamol in the five kinds of pharmaceutical prepara-
tions was determined. The results are in good agreement
with the manufacturersÕ stated contents of paracetamol
(as shown in Table 3).
Table 1
Recovery test of paracetamol Table 3
Determination of paracetamol in pharmaceutical preparations using
Added (in M) Found (in M) Recovery (%)
gold nanoparticles modified ITO electrode
2.00 · 10
7 1.93 · 10
7 96.5
5.00 · 10
7 4.86 · 10
7 97.2 Sample Stated Detected R.S.D. (%)
content content (n = 3)
1.00 · 10
6 0.97 · 10
6 97.0
2.50 · 10
6 2.51 · 10
6 100.4 Calpol 0.500 g/tablet 0.495 g/tablet 1.82
5.00 · 10
6 5.05 · 10
6 101.0 Crocin 0.500 g/tablet 0.495 g/tablet 0.79
1.00 · 10
5 1.01 · 10
5 101.0 Paracetamol 0.500 g/tablet 0.498 g/tablet 1.15
2.50 · 10
5 2.55 · 10
5 102.0 Paracip 0.500 g/tablet 0.495 g/tablet 1.81
5.00 · 10
5 5.09 · 10
5 101.8 Pyrigesic syrup 125 mg/5 ml 124 mg/5 ml 0.76
 R.N. Goyal et al. / Electrochemistry Communications 7 (2005) 803–807
4. Conclusions
The present work revealed the fact that gold nano-
particles modified ITO electrodes show a high electro-
catalytic activity towards the oxidation of paracetamol
exhibiting a 110 mV shift of the oxidation potential of
paracetamol in the cathodic direction and a marked
enhancement of the current response. A good linear
relationship between paracetamol concentration and
current response was obtained in the concentration
range of 2.0 · 10
7–1.5 · 10
3 M with a low detection
limit of 1.8 · 10
7 M. The gold nanoparticles modified
ITO electrode exhibited a stable and reproducible re-
sponse for paracetamol without any influence of physio-
logically common interferents (i.e., ascorbic acid,
glucose and urea) in 10-fold excess. The method has
been satisfactorily applied to the determination of para-
cetamol in pharmaceutical formulations.
Acknowledgements
One of the authors (N.B.) is thankful to the Council
of Scientific and Industrial Research, New Delhi for
awarding Junior Research Fellowship. The authors
(R.N.G. and M.O.) like to thank the bilateral program
between the Indian National Science Academy (INSA)
and the Japan Society for the Promotion of Science
(JSPS) joint program for the support of the cooperative
research.
References
[1] A. Wade (Ed.), Martindale the Extra Pharmacopoeia, 27th ed.,
The Pharmaceutical Press, London, 1979.
[2] J. Koch-Weser, New Engl. J. Med. 295 (1976) 1297–1300.
[3] S.P. Clissold, Drugs 32 (1986) 46–59.
[4] C.J. Nikles, M. Yelland, C.D. Marc, D. Wilkinson, Am. J.
Therap. 12 (2005) 80–91.
[5] K. Brandt, Drugs 63 (2003) 23–41.
807
[6] A.A.Taylor, et al., Baylor College of Medicine-Abstract from
Munich Meeting (Thirteenth IUPHAR Congress of Pharmacol-
ogy), 1998.
[7] National Asthma Campaign; Fact sheet 09.
[8] D.W. Cramer, B.L. Harlow, L.T. Ernstoff, K. Bohlke, W.R.
Welch, E.R. Greenberg, Lancet 351 (1998) 104–107.
[9] A.C. Moffat (Ed.), Clarks Isolation and Identification of Drugs,
second ed., The Pharmaceutical Press, London, 1986.
[10] M.K. Srivastava, S. Ahmed, D. Singh, I.C. Shukla, Analyst 110
(1985) 735.
[11] M.J. Ayaora Canada, M.I. Pascual Reguera, A. Ruiz Medina,
M.L. Fernandez de Cordova, A. Molina Diaz, J. Pharm. Biomed.
Anal. 22 (2000) 59.
[12] J.L. Vilchez, R. Blanc, R. Avidad, A. Navalon, J. Pharm. Biomed.
Anal. 13 (1995) 1119.
[13] O.W. Lau, S.F. Luk, Y.M. Cheung, Analyst 114 (1989) 1047–1051.
[14] S. Ravisankar, M. Vasudevan, M. Gandhimathi, B. Suresh,
Talanta 46 (1998) 1577–1581.
[15] J. Roy, P. Saha, S. Sultana, A.S. Kenyon, Bull. World Health
Org. 75 (1997) 19–22.
[16] M. Knochen, J. Giglio, B.F. Reis, J. Pharm. Biomed. Anal. 33
(2003) 191.
[17] M.L. Ramos, J.F. Tyson, D.J. Curran, Anal. Chim. Acta 364
(1998) 107.
[18] S. Bi, G. Wang, Y. Piao, D. Wang, X. Yin, Yanbian Daxue
Xuebao, Ziran Kexueban 26 (2000) 110–112.
[19] J.M. Zen, Y.S. Ting, Anal. Chim. Acta. 342 (1997) 175.
[20] F.Y. He, A.L. Liu, X.H. Xia, Anal. Bioanal. Chem. 379 (2004)
1062.
[21] N. Wangfuengkanagul, O. Chailapakui, Anal. Sci. 17 (2001) 349.
[22] I. Christie, S. Leeds, M. Baker, F. Keedy, P. Vadgama, Anal.
Chim. Acta 272 (1993) 145.
[23] I.C. Vieira, K.O. Lupetti, O.F. Filho, Quim. Nova 26 (2003) 39.
[24] R. Sandulescu, S. Mirel, R. Oprean, J. Pharmaceut. Biomed.
Anal. 23 (2000) 77.
[25] M.A.T. Gilmartin, J.P. Hart, Analyst 119 (1994) 2431.
[26] M. Lahav, A.N. Shipway, I. Willner, J. Chem. Soc. Perkin Trans.
2 (1999) 1925.
[27] A.N. Shipway, E. Katz, I. Willner, Phys. Chem. Phys. 1 (2000) 18.
[28] E. Katz, I. Willner, Wang, Electroanalysis 16 (2004) 19.
[29] J.A. Harnisch, A.D. Pris, M.D. Porter, J. Am. Chem. Soc. 123
(2001) 5829.
[30] S. Hrapovic, Y. Liu, G. Enright, F. Bensebaa, J.H.T. Luong,
Langmuir 19 (2003) 3958.
[31] A. Yu, Z. Liang, J. Cho, F. Caruso, Nano Lett. 3 (2003) 1203.
[32] J. Zhang, M. Kambayashi, M. Oyama, Electrochem. Commun. 6
(2004) 683.
[33] G.D. Christian, W.C. Purdy, J. Electroanal. Chem. 3 (1962) 363.