ORIGINAL PAPER

Electrooxidative behavior and determinationof trifluoperazine at multiwalled carbon nanotube-modifiedglassy carbon electrode

Burcu Dogan-Topal

Received: 18 September 2012 /Revised: 19 November 2012 /Accepted: 2 December 2012 /Published online: 15 December 2012# Springer-Verlag Berlin Heidelberg 2012

Abstract The mechanism of electrochemical oxidation oftrifluoperazine has been proposed on the basis of cyclic anddifferential pulse voltammetry at a multiwalled carbonnanotube-modified glassy carbon electrode. The modifiedelectrode exhibits catalytic activity, high sensitivity, andstability. The oxidation process exhibited an adsorption-controlled behavior. Also, depending on this adsorptioncontrol, a sensitive electroanalytical method for the deter-mination of trifluoperazine has been investigated by adsorp-tive stripping differential pulse voltammetry. Under theoptional conditions, the anodic peak current was linear tothe trifluoperazine concentration over the range of 2.08 10−8

M to 1.67 10−6M, and the limit of detection was 7.49 10−10

M. The modified electrode had good stability and repeat-ability, and it was successfully applied to the determinationof trifluoperazine in pharmaceuticals.

Keywords Trifluoperazine . Carbon nanotubes .

Voltammetry . Modified glassy carbon electrode .

Pharmaceuticals

Introduction

The interest in developing electrochemical sensing devicesfor use in clinical assay, process control, and environmen-tal monitoring is growing rapidly. The use of nanotech-nology in the field of health is possible in many areassuch as drug carrier imaging, nucleic acid analysis,nano-surgery, and drug analysis. Electrochemical sensors

based on nanostructured materials can cope for real sam-ples which did not have a complex composition andtime-consuming preparation steps.

Carbon nanotubes (CNTs) are one of the most importantnano-materials due to their high chemical stability, highsurface area, high mechanical properties, and unique elec-trical conductivity. Carbon-based electrodes are currently inwidespread use in electroanalytical chemistry, because oftheir rich surface chemistry, low cost, chemical inertness,low detection limit, and resistance to surface fouling [1–7].The electronic properties suggest that CNTs have the capa-bility to promote electron transfer reactions and improvesensitivity in electrochemistry, and thus, they are widelyused as electrode materials for drug analysis. Also, themodification of the electrode substrates with multiwalledcarbon nanotubes (MWCNTs) for use in analytical sensinghas been documented to result in low detection limits andhigh sensitivities. Multiwalled carbon nanotubes functional-ized with carboxylic acid group (MWCNTs–COOH) havehigh dispersion quality, binding activity for molecular rec-ognition, and redox activity of carboxylic acid groups on thesurface of MWCNTs. These functional groups attached onthe surfaces of the carbon nanotubes (CNTs) improve theiradsorption capability of trifluoperazine (TFPZ) in solution.Recently, the adsorptive stripping voltammetry (AdSV)technique has been reemergent amongst electroanalyticaltechniques through the use of CNT-modified electrodeswhere a thin porous layer of nanotubes is deposited whichis in electrical contact with a suitable electrode.

TFPZ belongs to phenothiazine derivatives, which is thelargest group of the main five classes of the antipsychotic,sedative, and antiemetic drugs. TFPZ is chemically named as10-[3-(4-methylpiperazin-1-yl) propyl]-2-(trifluoro-methyl)-10H-phenothiazine hydrochloride (Scheme 1). It is widelyused to control some psychotic disturbances such as depres-sion, agitation, anxiety, psychosis, and acute confusional state.

B. Dogan-Topal (*)Faculty of Pharmacy, Department of Analytical Chemistry,Ankara University, Tandogan,06100 Ankara, Turkeye-mail: doganb@ankara.edu.tr

J Solid State Electrochem (2013) 17:1059–1066DOI 10.1007/s10008-012-1967-1

It is a potent drug, approximately 20 times more potent thanchlorpromazine [8, 9].

Generally, the detection of TFPZ is performed withspectrophotometry [10, 11], HPLC [12], LC-MS [13],GC-MS [14], and voltammetry [15–19]. Electroanalyti-cal methods are widely used for the determination of awide range of drug compounds due to their low cost,less buffer consumption, sensitivity, selectivity, and rel-atively short analysis time interval; they also do notrequire extraction, evaporation, or complicated prepara-tion procedure when compared to other techniques. Theleast level of detection limit is almost 2.0 10−9M inother techniques [10–14]. Furthermore, the knowledgeof the electrochemical properties of a drug is an impor-tant pharmaceutical tool mostly because it can show the wayfor a better understanding of the drug's metabolic fate or invivo redox processes and pharmacological activity. The elec-trochemistry of TFPZ was studied with a potentiometric sen-sor [15], modified gold electrodes [16], carbon pasteelectrodes [17], wax-impregnated graphite electrode [18],and poly-ABSA/SWNT film-modified glassy carbon elec-trode [19]. With the potentiometric sensor, the linear concen-tration range between 1.00 10−5 and 1.00 10−2M with limit ofdetection (LOD) is 7.60 10−6M [15], and with the modifiedgold electrode, a linear concentration range between 5.00 10−7

and 3.00 10−5M with LOD is 3.00 10−8M [16]. With poly-ABSA/SWNT film-modified glassy carbon electrode, a linearrelation in the concentration range between 1.00 10−7 and 1.0010−5 with LOD is 1.00 10−9M. The published study comprisesthe electropolymerization step that is time consuming [19]. Inthese studies [15–19], the calibration range and detectionlimits are not sensitive as much as the proposed method withMWCNT-modified glassy carbon electrode (GCE) for TFPZdetermination.

This work aimed to study the detailed voltammetric be-havior and sensitive assay of TFPZ at a MWCNT-modifiedGCE using cyclic voltammetry (CV) and adsorptive strip-ping differential pulse voltammetry (AdSDPV). Also, elec-trocatalytic activity of MWCNTs for the oxidation of TFPZhas been explored by comparing its voltammetric responsesat MWCNT/GCE with that of GCE. For electrochemicalmechanism study, promethazine and cetirizine (Scheme 1)were used as model compounds with modified electrode.

This modified electrode was used for the analysis of TFPZin pharmaceutical dosage forms.

Experimental

Reagents and chemicals

TFPZ was purchased from Dr. F. Frik Co. Ltd. (Turkey).Model compounds, promethazine and cetirizine, were sup-ported from Günsa Güney Co. Ltd. (Turkey) and Deva Co.Ltd. (Turkey), respectively. Stock solutions (2.08 10−3M)were prepared in distilled water. Multiwalled nanotubeswere produced through chemical vapor deposition. Theyare purified to remove free amorphous carbon deposits andcatalyst metallic particles. They are purified to more than95 % C. They have an average diameter of 10 nm and anaverage length of 1.5 μm. COOH functionalized multi-walled carbon nanotubes (MWCNT–COOH)—COOHfunctionalization is approx 5 %, measured by X-ray photo-electron spectroscopy. MWCNT–COOH were obtainedfrom Dropsens. The different supporting electrolytes, phos-phate buffer (0.2 M H3PO4; 0.2 M NaH2PO4·2H2O; 0.2 MNa2HPO4; pH2.0–8.0), Britton–Robinson (BR) buffer(0.04 M H3BO3; 0.04 M H3PO4, and 0.04 M CH3COOH;pH2.0–10.0), and acetate buffer (0.2 M CH3COOH; pH3.5–5.5), were used for electrochemical measurements. Otherreagents used were of analytical grade, and their solutionswere prepared with bidistilled water.

Apparatus

Electrochemical measurements were carried out on theAUTOLAB-PGSTAT 30 electrochemical analytical in-strument that was monitored with a personal computerusing General Purpose Electrochemical Software (GPES)4.9 software (Eco Chemie, Utrecht, the Netherlands). Athree-electrode system was used, including a bare glassycarbon electrode (Φ03.0 mm) or MWNT-modified glassycarbon as a working electrode, an Ag/AgCl (BAS; 3 MKCl) electrode as a reference electrode, and a platinum wireas a counter electrode. pH was measured using a pH meter,model 538 (WTW, Austria), using a combined electrode

Scheme 1 The structure ofTFPZ (a), promethazine (b),and cetirizine (c)

1060 J Solid State Electrochem (2013) 17:1059–1066

(glass electrode–reference electrode) with an accuracy ofpH±0.05.

DPV conditions were given as follows: step potential,0.00795 V; modulation amplitude, 0.0505 V; modulationtime,0.05 s; interval time, 0.5 s. Average baseline correctionwas defined using a “peak width” of 0.01 V. Cyclic voltam-metric measurements were also realized by usingAUTOLAB-PGSTAT 30 system.

Preparation of MWCNT-modified electrode

The MWCNT suspension was prepared by dispersing0.5 mg of MWCNTs in 1 mL N, N-dimethlyformamideusing ultrasonic agitation during 2 h. The GCE was careful-ly polished with alumina slurry on a polishing cloth. Thecleaned GCE was coated by casting 2 μl of the blacksuspension of MWCNTs and dried in air (approximately12 h).

Analytical procedure

The prepared MWCNT-modified GC electrode was firstactivated in phosphate buffer (pH3.0) by cyclic voltammet-ric sweeps between 0.0 and 1.5 V potential range until stablecyclic voltammograms were obtained. After an accumula-tion of 180 s at 0.8 V with stirring, the differential pulsevoltammograms were recorded between 0.20 and 1.50 V.After all measurements, the MWCNT-modified GC electrodewas regenerated by successive potential scans (number ofscans03) in phosphate buffer solution (pH3.0) by cyclicvoltammetry. All electrochemical experiments were per-formed at room temperature.

Sample preparation

Ten pieces of StilizanR-coated tablets were weighed andpowdered in a mortar. A portion equivalent to a stocksolution of a concentration of about 1.0 10−3M wasaccurately weighed and transferred into a 10.0-mL cal-ibrated flask and completed to the volume with distilledwater. The contents of the flask were sonicated for30 min, and appropriate amounts of working solutionswere prepared by taking suitable aliquots of the clearsupernatant liquid and diluting them with the pH3.0phosphate buffer solutions.

To study the accuracy of the proposed method and tocheck the interferences from excipients used in thedosage form, recovery experiments were carried out.The concentration of TFPZ was calculated using thestandard addition method. For these experiments, knownamounts of pure drug were added to the earlier analyzedcoated tablet formulation of TFPZ. The nominal contentand recovery of the drug was calculated using the

corresponding regression equations of previously plottedcalibration plots.

Results and discussion

The detailed electrochemical data were investigated forTFPZ in this work. TFPZ is manifested on current–voltage curves recorded by CV and DPV on a bare andCNT-modified glassy carbon electrode by three anodicpeaks.

Influence of amount of MWCNTs

A different volume of 0.5 mg/mL MWCNTs (2–5–10–15 μl) was dropped to the electrode surface. Twomicroliters was chosen as the optimum amount for thepeak current response. After this amount, peak currentwas decreased. This is related to the thickness of thefilm. When it was too thick, the film conductivityreduced, and the film became not as stable as MWCNTscould leave off the electrode surface. Thus, it blocks theelectrode surface, and hence, the peak current decreases.Therefore, 2 μl MWCNT suspension solution was usedin the remaining studies.

Electrochemical behavior of TFPZ

Before starting the pH studies on MWCNT-modified GCEelectrode, the circumstances of the stripping parameterswere optimized at pH3.0 phosphate buffer. Accumulationtime and accumulation potential were individually opti-mized and chosen as 0.2 V and 60 s, respectively, by DPV.Next, these parameters are used for the pH experiments.

Figure 1 shows the differential pulse voltammograms ofTFPZ could be seen at bare (2) and modified (3) GCE in pH

2 22

1 1

3

3

3

1

0.383 0.633 0.883 1.133 1.383-0.10u

0.40u

0.90u

1.40u

1.90u

2.40u

Potential, V

Cur

rent

, A

Fig. 1 Differential pulse voltammograms of bare buffer (1); 8.32 10−6

M TFPZ on bare GCE (2), and MWCNT-modified GCE (3)

J Solid State Electrochem (2013) 17:1059–1066 1061

3.0 phosphate buffer. As is seen, the peak currents of TFPZgreatly enhanced, and also, the third peak potential consid-erably shifted from 1.34 to 1.28 V with MWCNT-modifiedGCE. These results clearly show the electrocatalytic effectof MWCNTs. Also, the repetitive cyclic voltammograms ofTFPZ and model compounds (promethazine and cetirizine)were studied in pH3.0 phosphate buffer (Fig. 2). As seen inFig. 2a, TFPZ exhibited three anodic peaks, the first peak at0.85 V, the second peak at 1.15 V, and the third peak at1.36 V by CV. Also, the peaks were seen on the anodicbranch at 0.280 V and on the cathodic branch at 0.230 Vmay be relating to COOH functionalized MWCNTs. At thesame time, these waves could be seen on supporting elec-trolyte voltammograms in Fig. 2a (1).

After first cycle, the new peak occurred at 0.63 V on theanodic branch by CV (Fig. 2a). On further successive cyclicvoltammograms, while the three anodic peak currents weredecreased, the new peak was increased. This new peak mayhave occurred based on the phenothiazine ring (Fig. 2b). Toexplain the TFPZ structure, promethazine and cetirizinewere studied by repetitive cyclic voltammograms. Prome-thazine exhibited two anodic peaks, the first peak at 0.73 Vand the second peak at 1.13 V by CV (Fig. 2b). After firstcycle, the new peak occurred at 0.60 V by CV as TFPZ.Cetirizine exhibited one anodic peak at 1.12 V by CV(Fig. 2c).

Influence of pH

It is well known that the pH of the supporting elec-trolyte has a major impact on the response in mostanalytical determinations of organic and inorganiccompounds. This parameter was examined for its in-volvement in the oxidation process on MWCNT/GCEelectrode. The pH-dependent oxidation of TFPZ wasstudied systematically using various buffers (Britton–Robinson, phosphate, acetate) in a pH range between2.0 and 10.0 by adsorptive stripping differential pulsevoltammetry. Within the range of pH2.0–10.0, the po-tential of three peaks shifted to less positive values(Fig. 3 and 4).

For pH<8, the first peak, at 0.74 V, was pH independent,with only the transfer of an electron. After pH8.00, the firstpeak became pH dependent, and the oxidation potential wasshifted to less positive values. The plot of the peak potential(Ep) vs. pH showed a straight line, which can be expressedby the following equation with standard error: Ep01,106.3(±9.91 101)−51.00 (±1.1 101) pH; r00.978. The slope of theequation is 51∼60 mV per pH unit, showing the samenumber of electrons and protons. As seen in Fig. 4, the

2

5

1

0.0280.2780.5280.7781.0281.2781.528-4-0.13x10

-4-0.03x10

-40.07x10

-40.17x10

-40.27x10

-40.37x10

0.2600.5100.7601.0101.2601.510

-4-0.137x10

-4-0.087x10

-4-0.037x10

-40.013x10

-40.063x10

-40.113x10

-40.163x10

-40.213x10

0.2360.4860.7360.9861.2361.486-4-0.120x10

-4-0.095x10

-4-0.070x10

-4-0.045x10

-4-0.020x10

-40.005x10

-40.030x10

-40.055x10

-40.080x10

-40.105x10

-40.130x10

Potential, V

Cur

rent

, A

a

b

c

Fig. 2 1 Bare pH3.00 phosphate buffer and successive cycle of therepetitive voltammograms (5; first cycle) for 6.24 10−5M TFPZ (a),promethazine (b), cetirizine (c) on MWCNT/GCE by cyclic voltam-metry. Scan rate is 100 mV/s

2 2

2

1

1

3

3

3

1

0.425 0.675 0.925 1.175 1.425-0.14u

0.36u

0.86u

1.36u

1.86u

2.36u

2.86u

Potential, V

Cu

rren

t,A

Fig. 3 DPAdS voltammograms of 8.32 10−6M TFPZ on MWCNT/GCE electrode. 1 pH3.00 phosphate; 2 pH4.70 acetate buffer; 3 pH7.00 BR buffer. Accumulation time, 60 s; accumulation potential,0.2 V for pH study

1062 J Solid State Electrochem (2013) 17:1059–1066

second peak (selected one for analytical determination) po-tential, at 1.10 V, is shifted to less positive values up to pH6.0. After pH6.0, the second peak disappeared. The plot ofthe peak potential (Ep) vs. pH showed one straight line(Fig. 4), which can be expressed by the following equation:Ep01,221 (±1.13 10

1)−59.37 (±2.65) pH; r00.999. The slopeof the equation is 59∼60 mV per pH unit, showing the samenumber of electrons and protons. The width at half height ofthe second TFPZ oxidation peak isW1/2 ∼95 mV, close to thetheoretical value of 90 mV for an electrochemical reactioninvolving the transfer of one electron [20]. It can be concludedthat the second oxidation peak of TFPZ occurs with thetransfer of one electron and one proton. The third peak poten-tial is pH independent in all pH levels. The width at half heightof the third TFPZ oxidation peak isW1/2 ∼79 mV, close to thetheoretical value of 90 mV for an electrochemical reactioninvolving the transfer of one electron and no proton, becauseof pH independence.

The intersection of the Ep–pH curves is located aroundpKa values of drugs. pH3.9 and pH8.1 may correspond tothe pKa values of TFPZ according to the literature (http://www.drugfuture.com/chemdata/trifluoperazine.html]. Asseen in the above equations, intersection points of the firstpeak are close to the pKa2 value of TFPZ. This can also beexplained by changes in protonation of the acid–base func-tions in the molecule.

The maximum peak current value was obtained at acidicpH value. The current of the peak was increased to pH3.0, andthen, the peak current decreases continuously. >The pH3.0phosphate buffer at which the peak current reached a maxi-mum was chosen as the supporting electrolyte for the quanti-tative determination part of the study. The second peak waschosen with respect to sharp response and better peak shapefor the calibration equation of pharmaceutical dosage forms.

Effect of scan rate

Useful information involving electrochemical mechanismusually can be acquired from the relationship between peakcurrent and scan rate. Scan rate studies, between 5 and100 mVs−1, were carried out to assess whether the processeson the MWCNT-modified GCE were under diffusion or ad-sorption controlled in 2.08 10−5M TFPZ solutions. The linearincrease in the oxidation of peak current with the scan rateshowed that the adsorption control process is more dominant.

The equations are given below for phosphate buffer atpH3.0: Ip1 (μA)016.92 (±1.19) v (Vs−1)+0.035 (±6.1110−2); r00.992 for the first peak; Ip2 (μA)040.04 (±2.35)v (Vs−1)+0.13 (±1.21 10−1); r00.995 for the second peak;Ip3 (μA)022.25 (±2.15) v (Vs−1)−0.14 (±1.11 10−1); r00.986 for the third peak. A plot of logarithm of peak currentsvs. the logarithm of scan rate gave a straight line with slopesof 0.79, 0.76, and 1.10. The obtained slopes are close to thetheoretical value of 1.0, which is expressed for an idealreaction of surface species and confirming adsorption-controlled electrode process [21]. The obtained equationsare: log Ip1 (μA)00.79 (±6.7 10−2) log v (Vs−1)+0.96(±1.14 10−1); r00.989 for the first peak; log Ip2 (μA)00.76 (±6.28 10−2) log v (Vs−1)+1.32 (±1.07 10−1); r00.990 for the second peak; log Ip3 (μA)01.10 (±7.5710−2) log v (Vs−1)+1.36 (±1.29 10−1); r00.992 for the thirdpeak. According to the obtained results from all the oxida-tion peaks, the electrochemical reaction was found as anadsorption-controlled process.

All peak potentials shifted to more positive values withincrease in the scan rates. The linear relation between peakpotential and logarithm of scan rate can be expressed as: Epa1(V)00.898 (±1.32 10−3)+0.051 (±7.75 10−4) log v (Vs−1); r00.999 for the first peak; Epa2 (V)01.20 (±4.31 10−3)+0.064(±2.53 10−3) log v (Vs−1); r00.998 for the second peak; Epa3(V)01.39 (±3.12 10−3)+0.045 (±1.83 10−3) log v (Vs−1); r00.998 for the third peak. These behaviors were consistent withthe electrochemical nature of the reaction in which the elec-trode reaction is coupled with an irreversible follow-up chem-ical step for each peak [22].

Possible mechanism of TFPZ

The anodic behavior of TFPZ is investigated as details usingCV techniques in different buffer solutions and pH values.CV is the most suitable method for the investigation of theredox behavior of drug active compounds which can giveinsights into their metabolic fates [23, 24]. To identify theresponsible group of the oxidation steps, the oxidation ofTFPZ was compared with some model compounds andalready published studies related with the phenothiazineand piperazine rings. Therefore, several measurements indifferent supporting electrolytes using the CV method were

pH

1 2 3 4 5 6 7

Po

ten

tia

l, V

0.80

0.85

0.90

0.95

1.00

1.05

1.10

1.15

Fig. 4 Effect of pH on TFPZ anodic peak potential of first peak (a)and second peak (b); TFPZ concentration 8.32 10−6M. Circles acetatebuffer, squares phosphate buffer, diamonds BR buffer

J Solid State Electrochem (2013) 17:1059–1066 1063

performed in order to obtain such information. Although theexact oxidation pathways were not determined, some con-clusions about the possible electroactive centers underworking conditions could be reached. Both phenothiazineand piperazine rings may be shown an electrooxidationresponse on CV. Both redox responses were compared withthe selected model compounds (promethazine, cetirizine)and the similar compounds in the literature (trazodone,flunarazine, nefazodone, quetiapine, chlorpromazine)[25–29]. Our results showed that the phenothiazine andpiperazine oxidations may have occurred in TFPZ com-pound. Phenothiazine oxidation occurs in two- and one-electron processes [30]. Also, the repetitive cyclic voltam-mograms of promethazine (phenothiazine ring) can be seen inFig. 2b. It was assumed that the first oxidation step occursbecause of the thiol atom, while the second reversible oxida-tion step occurs at the nitrogen atom on the phenothiazine ring[29]. The pKa values of the phenothiazines are 9.1 for prom-ethazine, 9.4 for promazine [31], and 9.3 for chlorpromazine(http:/ /chrom.tutms.tut .ac.jp/JINNO/DRUGDATA/62chlorpromazine.html), ‘considering the above comparisonand the break points of Ep vs. pH plots for TFPZ which wereobtained at about pH 8.0.

Also, taking into account that the obtained results andliterature knowledge closely matched, it may be assumedthat the seconds response of TFPZ may be located on thepiperazine moiety, which represented a typical redox systemwith two electrons in acidic and basic media [25–28]. Thus,I might postulate when the aliphatic nitrogen on the piper-azine ring, the piperazine moiety was protonated, oxidationoccurred on the nitrogen with the removal of a proton.[25–28]. For all model substances, the intersection at aboutpH7.5 was supposed to correspond to the second pKa valueof piperazine moiety. Also, pKa values of some piperazineswere studied by Khalili [32]. The pKa values of piperazinewere compared with published data to validate the procedureused. The piperazine ring has two pKa values: pKa1 is ∼3.81and pKa2 is ∼8.38 [32], considering the above comparison andthe break point of Ep vs. pH plots for TFPZ which wereobtained at about pH8.0. Hence, the anodic oxidation mech-anism of TFPZ may be related with the phenotiazine andpiperazine ring.

Influence of accumulation potential and time

The influences of accumulation potential and accumula-tion time have been studied by differential pulse vol-tammetric method as these could affect the amount ofadsorption of TFPZ at the electrode. Figure 5a displaysthe resulting peak current vs. accumulation potential for8.32 10−6M TFPZ in pH3.0 phosphate buffers. An adsorp-tion potential of 0.80 V was found for analytical determina-tion. The peak current increases greatly as the accumulation

time is increased from 30 to 240 s. For accumulation timegreater than 180 s, the peak current was almost con-stant; (Fig. 5b), so 180 s was chosen as accumulationtime. Hence, an accumulation time and potential wasapplied as 180 s at 0.8 V, respectively, with stirring, andthe differential pulse voltammograms were recorded between0.20 and 1.50 V.

Analytical parameters and validation of the method

Adsorptive stripping differential pulse voltammetrictechniques are effective and rapid electroanalytical tech-niques with well-established advantages, including gooddiscrimination against background currents and low de-tection limits. AdSDPV for the MWCNT-modified GCelectrode was developed for the quantitative determina-tion of TFPZ in pH3.0 phosphate buffer solution which

a

Potential, V

0.0 0.2 0.4 0.6 0.8 1.0 1.2 1.4

Cu

rren

t,A

0.0

0.2

0.4

0.6

0.8

1.0

b

Time, s

0 50 100 150 200 250 300

Cu

rren

t,

A

0.2

0.4

0.6

0.8

1.0

1.2

1.4

1.6

1.8

Fig. 5 a Effect of accumulation potential on the peak current with 60 sof accumulation time. b Effect of accumulation time on the peakcurrent, with an accumulation potential at 0.8 V for 1.67 10−6M TFPZin pH3.00 phosphate buffer using DPAdS method on MWCNT/GCEelectrode

1064 J Solid State Electrochem (2013) 17:1059–1066

was proved to be the best medium for the analyticalapplications. Accumulation potential and accumulationtime of 0.8 V and 180 s, respectively, were selectedand applied for further studies. The plot of the calibra-tion curve was linear between 2.08 10−8 and 1.67 10−6Mfor the AdSDPV method (Fig. 6). Characteristics ofthese graphs are reported in Table 1. The precision ofthe method was investigated by repeatedly (n05) measur-ing the peak current of TFPZ within a day (repeatability),over three consecutive days (reproducibility of the samemodified electrode), and over three consecutive drop-pings (reproducibility of renewed modified electrode).Also, in Table 1, other necessary validation parameterssuch as LOD, limit of quantitation (LOQ), precision,

and accuracy were listed according to the literature[33–35].

Freshly prepared and aged (+4 °C, in the dark) TFPZsolutions were compared for confirming the stability ofthe solutions. The results demonstrated that the workingreference solutions were stable for a period of up to aweek.

Tablet analysis

In electrochemical studies, the pretreatment was notrequired for the sample preparation such as time-consuming extraction, evaporation, or filtration stepsprior to the analysis. On the basis of the above results,the proposed method for the assay of TFPZ was appliedto direct determination in coated tablet dosage formsusing the related calibration straight line (Table 2).The accuracy of the proposed method was determinedby its recovery during spiked experiments. In order todetect interactions of excipients, the standard additiontechnique was applied to the same pharmaceutical prep-arations, which were analyzed by the calibration curve.The results indicated the validity of the proposed tech-niques for the determination of TFPZ in coated tabletdosage form (Table 2). The accuracy of the analysis ofall methods was determined by calculating the relativeerror (bias in percent) between the measured mean con-centrations and actual concentration [33–35] (Table 2).

Conclusion

A MWCNT/GCE has been successfully utilized for theadsorptive stripping voltammetric determination ofTFPZ in standard laboratory and real pharmaceuticalsamples. The detection limit of 7.49 10−10M was obtained.

0.414 0.664 0.914 1.164 1.414-0.06u

0.19u

0.44u

0.69u

0.94u

1.19u

1.44u

Potential, V

Cur

rent

, A

11

5

4

32

Fig. 6 DPAdS voltammograms on MWCNT/GCE electrode in pH3.00 phosphate buffer for the determination of TFPZ; 1 blank, 2containing 4.17 10−8M, 3 1.67 10−7M, 4 4.17 10−7M, 5 1.67 10−6M

Table 1 Regression data of the calibration lines for determination ofTFPZ by AdSDPV

MWCNT/GCE

Measured potential (V) 1.03

Linearity range (M) 2.08 10−8–1.67 10−6

Number of point 7

Slope (μAM–1) 1.20 106

Intercept (μA) −0.054

Correlation coefficient 0.995

SE of slope 5.55 104

SE of intercept 4.03 10−2

LOD 7.49 10−10

LOQ 2.50 10−9

Within day reproducibility of peak current(RSD %)

1.08

Between day reproducibility of peak current(RSD %)

1.98

Between modified electrode reproducibilityof peak current (RSD %)

2.87

Table 2 Results obtained for TFPZ determination in pharmaceuticaldosage form using MWCNT/GCE

MWCNT/GCE

Labeled claim (mg) 5.00

Amount founda (mg) 5.09

RSD% 0.67

Bias% −1.8

Added TFPZ (mg) 1.00

Found TFPZ (mg) 0.98

Average recovery% 98.05

RSD% of recovery 1.05

Bias% 1.95

a Each value is the mean of five experiments

J Solid State Electrochem (2013) 17:1059–1066 1065

To the best of our knowledge, this limit of detection is thelowest detection limit which has been reported in this litera-ture for TFPZ detection using electrochemical techniques.

The proposed method using a MWCNT/GCE benefitsfrom advantages such as high sensitivity, very low detectionlimit with reasonable reproducibility, easy handling, resis-tance against surface fouling, and low cost. In the previouslyreported method, poly-ABSA/SWNT film-modified GCE[19] is time-consuming, because of the polymerization step,and the other electrochemical methods [15–18] are not assensitive as the newly developed method. Hence, newlydeveloped methods are inexpensive, rapid, and simple meth-ods for determining accurate TFPZ concentrations withapplications in the pharmaceutical quality control laboratoryas well as possible medicinal and toxicological applications.

References

1. Balasubramanian K, Burghard M (2006) Anal Bioanal Chem385:452–468

2. Gooding JJ (2005) Electrochim Acta 50:3049–30603. Baughman RH, Zakhidov AA, de Heer WA (2002) Science

297:787–7924. Katz E, Willner I (2004) Chem Phys Chem 5:1085–11045. Yin T, Wei W, Zeng J (2006) Anal Bioanal Chem 386:2087–20946. Angeles GA, Loĭpez BP, Pardave MP, Silva MTR, Alegret S

(2008) Carbon 46:898–9067. Li Y, Wang P, Wang L, Lin X (2007) Biosens Bioelectron

22:3120–31258. Bruera E, Nemann CM (1998) Psychology 7:346–3589. Holroyd S, Seward RL (1999) Clin Pharmacol Ther 66:323–325

10. Basavaiah K, Krishnamurthy G (1998) Talanta 46:665–67011. Basavaiah K, Krishnamurthy G (1998) Talanta 47:59–6612. Abdel-Moety EM, Al-Rashood KA, Rauf A, Khattab NA (1996) J

Pharm Biomed Anal 14:1639–1644

13. Kumazawa T, Seno H, Watanabe-Suzuki K, Hattori H, Ishii A,Sato K (2000) J Mass Spectr 35:1091–1099

14. Maurer H, Pfleger K (1984) J Chromatogr 306:125–14515. Hassan AK, Ameen ST, Saad B, Al-Aragi SM (2009) Anal Sci

25:1295–129916. Huang F, Yan QP, Zheng BZ (2005) Wuhan Univ J Nat Sci 10:43517. Peng TZ, Yang ZP, Lu RS (1990) Acta Pharmaceutica Sinica

25:277–28318. Jarbawi TB, Heineman WR (1986) Anal Chim Acta 186:11–1919. Jin G, Huang F, Li W, Yu S, Zhang S, Kong J (2008) Talanta

74:815–82020. Brett CMA, Oliveira-Brett AM (1993) Cyclic voltammetry and

linear sweep techniques. In: Electrochemistry: principles, methodsand applications. Oxford University Press, UK, pp 174–198

21. Laviron E, Roullier L, Degrand C (1980) J Electroanal Chem112:11–23

22. Brown ER, Large RF (1964) In: Weissberger A, Rossiter BW (eds)Physical methods of chemistry. Wiley Interscience, Rochester,p 423

23. Wang J (ed) (1988) Electroanalytical techniques in clinicalchemistry and laboratory medicine. VCH, New York

24. Kissinger PT, Heineman WR (eds) (1996) Laboratory techniquesin electroanalytical chemistry, 2nd edn. Marcel Dekker, New York

25. Kauffmann JM, Vire JC, Patriarche GJ, Nunez-Vergara LJ, SquellaJA (1987) Electrochim Acta 32:1159

26. Uslu B, Yilmaz N, Erk N, Ozkan SA, Senturk Z, Biryol I (1999) JPharm Biomed Anal 21:215–220

27. Uslu B, Özkan SA (2002) Anal Chim Acta 462:49–5728. Ozkan SA, Dogan B, Uslu B (2006) Microchim Acta 153:27–3529. Parvin MH (2011) Electrochem Commun 13:366–36930. Grimshaw J (2000) Electrochemical reactions and mechanism in

organic chemistry, 1st edn. Elsevier, Amsterdam31. Lin C, Liao W, Chen K, Lin W (2003) Electrophoresis 24:3154–

315932. Khalili F, Henni A, East ALL (2009) J Chem Eng Data 54:2914–

291733. Riley CM, Rosanske TW (eds) (1996) Development and validation

of analytical methods. Elsevier Science Ltd, New York34. Ermer J, Miller JHMB (eds) (2005) Method validation in pharma-

ceutical analysis. Weinheim, Wiley-VCH Pub35. Swartz ME, Krull IS (1997) Analytical method development and

validation. Marcel Dekker, New York

1066 J Solid State Electrochem (2013) 17:1059–1066