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

Contents lists available at ScienceDirect

Colloids and Surfaces B: Biointerfaces

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lectrochemical behavior and voltammetric determination of paracetamol onafion/TiO2–graphene modified glassy carbon electrode

ang Fan ∗, Jin-Hang Liu, Hai-Ting Lu, Qin Zhangollege of Chemistry and Chemical Engineering, Xinyang Normal University, Xinyang 464000, PR China

r t i c l e i n f o

rticle history:eceived 14 January 2011eceived in revised form 19 February 2011

a b s t r a c t

The TiO2–graphene (TiO2–GR) nanocomposite for paracetamol electrochemical sensing is described. Theelectrochemical behavior of paracetamol at the Nafion/TiO2–GR composite film modified glassy carbonelectrode (GCE) was investigated by cyclic voltammetry. The results showed that the incorporation of

ccepted 25 February 2011vailable online 8 March 2011

eywords:aracetamolraphene

TiO2 nanoparticles with graphene significantly enhanced the electrochemical reactivity and voltammetricresponse of paracetamol. In addition, Nafion acts as an effective solubilizing agent and antifouling coatingin the fabrication of the modified electrode. This electrochemical sensor exhibits excellent analyticalperformance for paracetamol detection at physiological pH with detection limit of 2.1 × 10−7 M, linearrange of 1–100 �M and reproducibility of 3.6% relative standard deviation.

iO2–graphene nanocompositelectrochemical sensor

. Introduction

Paracetamol (acetaminophen, N-acetyl-p-aminophenol) isidely used as an antipyretic and analgesic drug. It is an effective

nd safe analgesic agent used for the relief of mild to mod-rate pain associated with headache, backache, arthritis andostoperative pain [1]. It is also used for reduction of fevers ofiral and bacterial origin. Paracetamol relieves pain and fevery inhibiting prostaglandin’s synthesis in the central nervousystem and sedating hypothalamic heat-regulating center [2]. Asweak acid with pKa of 9.5, paracetamol rapidly gets absorbed

nd distributed after oral administration and is easily excretedn urine [3]. Generally, paracetamol does not exhibit any harmfulide effects. However, hypersensitivity or overdoses of parac-tamol leads to the formation of some liver and nephrotoxicetabolites. Moreover, the hydrolytic degradation product of

aracetamol is 4-aminophenol which can cause teratogenic effectnd nephrotoxicity. This species can be found in pharmaceuticalreparations as a degradation product of paracetamol or as aynthetic intermediate [4]. Thus, the development of simple,ensitive and accurate analytical methods for determination ofaracetamol in pharmaceutical preparations and human plasma

s of great importance. To date, electrochemical techniques haveeen widely explored for paracetamol detection, which havehe advantages of high sensitivity, less time-consuming and lowosts 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).

927-7765/$ – see front matter © 2011 Elsevier B.V. All rights reserved.oi:10.1016/j.colsurfb.2011.02.041

© 2011 Elsevier B.V. All rights reserved.

trode surface, paracetamol only exhibits sluggish voltammetricresponse. Thus, considerable efforts have been devoted to developchemically modified electrodes to enhance the voltammetricresponse and analytical performance for paracetamol detection[5–16].

Graphene-based electrochemical sensors have recently exhib-ited excellent analytical performance for small biomoleculesdetection [17–20]. Owing to its extraordinary electronic trans-port properties and high electrocatalytic activities, graphenegreatly promotes the electrochemical reactivity of biomoleculeson the modified electrode surface. Furthermore, the unique two-dimensional crystal structure of graphene makes it extremelyattractive as a support material for metal and metal-oxidecatalyst nanoparticles [21]. These graphene-based hybrid mate-rials have shown greater versatility as enhanced materials forelectrochemical sensors application [22–28]. Most recently, wedeveloped an effective hydrothermal method for the preparationof TiO2–graphene (TiO2–GR) nanocomposite [29]. Owing to its highadsorptivity and good biocompatibility, the incorporation of TiO2nanoparticles with graphene significantly promotes the electro-chemical sensing performance for dopamine detection.

In this paper, we prepared the Nafion/TiO2–GR composite filmmodified glassy carbon electrode (GCE) for electrochemical sens-ing of paracetamol. Nafion, the widely used perfluorosulfonatedpolymer, acts as an effective solubilizing agent for the TiO2–GR

nanocomposite, as well as an antifouling coating to reduce theinterference of the surface-active macromolecules. The electro-chemical behavior of paracetamol on the Nafion/TiO2–GR film wasinvestigated in detail. This electrochemical sensing interface exhib-ited excellent performance towards paracetamol detection, which

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stablished an effective sensing and screening platform for certainharmaceutical preparations.

. Experimental

.1. Apparatus and reagents

Paracetamol, ascorbic acid (AA) and dopamine (DA) and N,N-imethylformamide (DMF) were obtained from Aladdin Chemistryo., Ltd. Nafion (5 wt.% in lower aliphatic alcohols and water) wasurchased from Sigma–Aldrich. All other chemicals were of analyt-

cal reagent grade and used as received. Water used throughout allxperiments was purified with the Millipore system.

All electrochemical experiments were performed with a CHI50 C electrochemical workstation (CH Instruments, Shanghai,hina). A conventional three-electrode system was used for alllectrochemical experiments, which consisted of a platinum wires counter electrode, an Ag/AgCl/3 M KCl as reference electrode,nd a bare or modified glassy carbon electrode (3 mm diameter) asorking electrode.

.2. Preparation of modified electrode

The as-prepared TiO2–GR nanocomposite [29] was dispersed inMF containing 2.5% (V/V) Nafion with ultrasonication for 1 h to gethomogenous suspension (1 mg mL−1). Then, 5 �L of the suspen-

ion was dropped onto the surface of freshly polished glassy carbonlectrode (GCE) and dried at room temperature, resulting in theafion/TiO2–GR modified GCE (Nafion/TiO2–GR/GCE). For compar-

son, 5 �L of the homogenous suspension (1 mg mL−1) of graphenen DMF containing 2.5% (V/V) Nafion was coated on bare GCE tobtain the Nafion/GR modified GCE (Nafion/GR/GCE).

. Results and discussion

.1. Electrochemical behavior of paracetamol onafion/TiO2–GR/GCE

Fig. 1 depicts the cyclic voltammograms (CVs) of paraceta-

ol on the bare GCE, Nafion/GR/GCE and Nafion/TiO2–GR/GCE

n 0.1 M PBS (pH 7.0), respectively. On the bare GCE (Fig. 1a),aracetamol shows an irreversible redox behavior with small andndefined redox peaks. In contrast, on the Nafion/GR/GCE (Fig. 1b),he anodic and cathodic peak currents are significantly increased

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ig. 1. CVs of 1.0 mM paracetamol on the (a) bare GCE, (b) Nafion/GR/GCE and (c)afion/TiO2–GR/GCE in 0.1 M PBS (pH 7.0), at scan rate of 50 mV s−1.

iointerfaces 85 (2011) 289–292

with peak potentials located at 0.575 and 0.510 V, respectively. Theremarkably enhanced voltammetric response of paracetamol onthe Nafion/GR/GCE can be reasonably ascribed to the large spe-cific surface area and electrocatalytic activity of graphene, whichimproves the absorption efficiency and electrochemical reactiv-ity of paracetamol [5]. In the case of Nafion/TiO2–GR/GCE, a pairof well-defined and quasi-reversible redox peaks correspondingto 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 thaton Nafion/GR/GCE with a negative shifting of 65 mV. Moreover,oxidation peak current significantly increases to 44.8 �A, whichis 1.9 times higher than that on Nafion/GR/GCE. These resultsdemonstrated that the electrochemical reactivity of paracetamol isremarkably improved on the Nafion/TiO2–GR composite film. It issuggested that, owing to its high adsorptivity and good biocompat-ibility [6,30–33], TiO2 nanoparticles effectively modify the surfacechemistry of graphene sheets, which provides an efficient interfaceand microenvironment for the electrochemical reaction of parac-etamol. In addition, it was observed that Nafion can be used as aneffective solubilizing agent for the TiO2–GR nanocomposite to forma well-dispersed suspension, as well as an antifouling coating toreduce the interference of the surface-active macromolecules [34].

3.2. The redox mechanism of paracetamol onNafion/TiO2–GR/GCE

The effect of scan rate on the anodic and cathodic peakcurrent of paracetamol on the Nafion/TiO2–GR/GCE was inves-tigated. As shown in Fig. 2, the anodic and cathodic peakcurrents increase linearly as the scan rate grows from 50 to300 mV s−1. The linear relationship between the peak currentand the scan rate was obtained with the linear regressionequation as: Ipa/�A = −40.79–0.5785 v/mV s−1 (R = 0.9933) andIpa/�A = 32.04 + 0.3529 v/mV s−1 (R = 0.9948), respectively. Thisresult 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, plottingthe 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. Accordingto Laviron’s equation [35], the slops of the lines are equal to2.3RT/(1 − ˛)nF and −2.3RT/˛nF, respectively. Therefore, the elec-

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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 thepeak current vs. scan rate.

Y. Fan et al. / Colloids and Surfaces B: Biointerfaces 85 (2011) 289–292 291

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ig. 3. CVs of 1.0 mM paracetamol on Nafion/TiO2–GR/GCE in 0.1 M PBS with pHalues of 4.0, 5.0, 6.0, 7.0 and 8.0. Insert, the plot of formal potential vs. pH value.can rate: 50 mV s−1.

ron transfer coefficient (˛) and the electron transfer number (n) arealculated to be 0.63 and 1.9, respectively. The adsorbed amountf paracetamol on the surface of Nafion/TiO2–GR/GCE was fur-her calculated by the following equation: ip = n2F2A� v/4RT [35].ased on the relationship of ip with v, the value of the sur-

ace concentration of the paracetamol (� ) was obtained withhe results as 3.24 × 10−9 mol cm−2, which is higher than that3.7 × 10−10 mol cm−2) at the PAY/nano-TiO2/GCE [6], indicatingncreased adsorptivity of the Nafion/TiO2–GR composite film.

The effect of pH on the redox reaction of paracetamol athe Nafion/TiO2–GR/GCE was investigated in the range of pH.0–8.0. As shown in Fig. 3, the redox peak shifted negatively with

ncreasing solution pH, indicating that proton is involved in theedox reaction of paracetamol. A good linear relationship can bestablished between the formal potential (E0′

) and solution pHith the linear regression equation as: Ep/V = 0.8592–0.04860pH

R = 0.9940). Based on the equation dEp/dpH = 0.059�/˛n, theroton number (�) was estimated to be 1. Thus, the electro-hemical reaction of paracetamol on the Nafion/TiO2–GR film is ane-proton and two-electron process, which is in agreement withhe literature reports [5,8].

.3. Voltammetric determination of paracetamol

The voltammetric determination of paracetamol was carriedut in 0.1 M PBS (pH 7.0) using differential pulse voltammetryt the Nafion/TiO2–GR/GCE. Fig. 4 depicts the differential pulseoltammograms (DPVs) of various concentrations of paraceta-

ol. The peak current increases linearly against the concentration

f paracetamol within the range of 1–100 �M. The calibrationurve for paracetamol shows two linear segments: the first lin-ar segment increases from 1 to 20 �M with the linear regressionquation of Ipa/�A = −0.02412–0.1649cparacetamol/�M (R = 0.9962),

able 1omparison of the performances of some paracetamol electrochemical sensors.

Modified electrodes pH used Detection

Graphene/GCE 9.3 3.2 × 10−8

PAY/nano-TiO2/GCE 7.0 2.0 × 10−6

MWCNT-BPPGE 7.5 1.0 × 10−8

C60/GCE 7.2 0.5 × 10−4

PANI-MWCNTs/GCE 5.5 2.5 × 10−7

C–Ni/GCE 3.0 6.0 × 10−7

Nafion/TiO2–graphene/GCE 7.0 2.1 × 10−7

Fig. 4. DPVs of 1.0, 2.0, 4.0, 6.0, 8.0, 10, 20, 40, 60, 80 and 100 �M paracetamolon Nafion/TiO2–GR/GCE in 0.1 M PBS (pH 7.0). Insert, the plot of peak current vs.paracetamol concentration.

and the second linear segment increases up to 100 �M with thelinear regression equation of Ipa/�A = 4.049–0.3472cparacetamol/�M(R = 0.9968). The first linear region in the calibration curve can beascribed to an absorption process of paracetamol to form a sub-monolayer, and the second linear region was a process for theformation 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 werecompared with the earlier reports in Table 1. It can be seen that thisnew method could be applied for paracetamol detection in neutralbuffer solution (pH 7.0) with low detection limit and wide linearrange.

The long-term stability of the Nafion/TiO2–GR/GCE electro-chemical sensor was investigated by examining its currentresponse during storage in a refrigerator at 4 ◦C. The electrochem-ical sensor exhibited no obvious decrease in current responsein the first week and maintained about 93% of its initial valueafter two weeks. The relative standard deviation (RSD) of theNafion/TiO2–GR/GCE in response to 50 �M paracetamol for tenmeasurements was 3.6%, indicating the good reproducibility.

In biological samples, paracetamol generally suffers from theinterferences of ascorbic acid (AA) and dopamine (DA). Thus, exper-iment with interferences including AA and DA was performed totest the selectivity of the Nafion/TiO2–GR sensing platform. Asshown in Fig. 5, paracetamol exhibits well-defined DPV wave withgood separations from AA and DA. Therefore, it could be possiblefor 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 wereground to powder and dissolved in 0.1 M PBS (pH 7.0). Usingthis method, the concentration of paracetamol was detected to be493 mg/tablet, which is in good agreement with content of parac-etamol provided by the manufacture.

limit (M) Linear range (�M) References

0.1–20 [5]12–120 [6]

0.01–20 [7]50–1500 [8]

1–100 [9]2–230 [10]1–100 This work

292 Y. Fan et al. / Colloids and Surfaces B: B

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ig. 5. DPVs recorded on Nafion/TiO2–GR/GCE with AA (0.2 mM), DA (0.2 mM) andaracetamol (0.4 mM) in 0.1 M PBS (pH 7.0).

. Conclusions

In summary, we have studied the electrochemical behavior ofaracetamol on the Nafion/TiO2–GR composite film modified elec-rode. The results indicate that the Nafion/TiO2–GR nanocompositean provide a favorable interface and microenvironment for thelectrochemical reaction of paracetamol. The composite film mod-fied electrode was successfully employed for the voltammetricetermination of paracetamol with low detection limit, wide linearange and good selectivity. We also demonstrated the applicationf Nafion/TiO2–GR/GCE for paracetamol detection in commercialablets with satisfactory results.

cknowledgements

This work was financially supported by the National Natural Sci-nce Foundation of China (No. 21002082) and the Key Project ofhinese Ministry of Education (No. 210129).

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iointerfaces 85 (2011) 289–292

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