Research Article Square Wave Voltammetric...
9
Hindawi Publishing Corporation International Journal of Electrochemistry Volume 2013, Article ID 627854, 8 pages http://dx.doi.org/10.1155/2013/627854 Research Article Square Wave Voltammetric Determination of 2-Thiouracil in Pharmaceuticals and Real Samples Using Glassy Carbon Electrode Naveen M. Gokavi, Vijay P. Pattar, Atmanand M. Bagoji, and Sharanappa T. Nandibewoor P. G. Department of Studies in Chemistry, Karnatak University, Dharwad 580003, India Correspondence should be addressed to Sharanappa T. Nandibewoor; [email protected] Received 19 September 2013; Revised 19 November 2013; Accepted 3 December 2013 Academic Editor: Mar´ ıa Isabel Pividori Copyright © 2013 Naveen M. Gokavi et al. is is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. A simple and rapid method was developed using cyclic and square wave voltammetric techniques for the determination of trace- level sulfur containing compound, 2-thiouracil, at a glassy carbon electrode. 2-thiouracil produced two anodic peaks at 0.334V and 1.421 V and a cathodic peak at −0.534 V. e square wave voltammetry of 2-thiouracil gave a good linear response in the range of 1–20 M with a detection limit of 0.16 M and quantification limit of 0.53 M (0.0679 g/g), which is in good agreement as per IUPAC definition of trace component analysis (100 g/g). e obtained recoveries range from 98.10% to 102.1%. e proposed method was used successfully for its quantitative determination in pharmaceutical formulations and urine as real samples. 1. Introduction In order to meet the growing demands for the new drugs (less costly, quite effective, and with minimum side effects) to fight against diseases, newer drugs are being pushed into the market at a greater extent that it has become difficult to keep abreast of their merits and demerits; so, a strict control on the quality of the drugs and their therapeutic actions become important. Hence, the pharmaceutical analysis plays a pivotal role in quality assurance. iouracil refers both to a specific molecule consisting of a sulfated uracil and a family of molecules based upon the structure. e substance is historically relevant in the preparation of antithyroid drug. Sulydryl compounds are known to undergo electrochem- ical oxidation at solid electrodes, but their oxidation occurs at relatively high potentials [1, 2]. It was characterized for the electrocatalytic oxidation of sulydryl compounds. 2- thiouracil (Scheme 1) and its derivatives also act as selective inhibitors of nitric oxide synthase (NOS) [3]. e adminis- tration of 2-thiouracil in chicken has been found to cause increase in total protein content and decrease in DNA content [4]. Results of some derivatives of 2-thiouracil, such as propy- lthiouracil, which was used as antithyroid drug, produced thyroid cancers in human and in some animals such as mice, rats, and hamsters [5]. Several methods have been reported for the determination of 2-thiouracil in complex physiological samples such as liquid chromatography coupled with electrochemical detection [6] and spectral studies [7]. However, these methods suffer from some disadvantages such as high cost, long analysis time, sample pretreatment, low sensitivity and selectivity, which make them unsuitable for routine analysis. In most of the chemical oxidations of 2-thiouracil, S–S linked dimer is obtained as the major product [8–10]. However electrochemical oxidation studies of 2-thiouracil has not attracted much attention. Hence it was considered interesting to study electrochemical oxidation of 2-thiouracil at glassy carbon electrode using square wave voltammetry. e advance in experimental technique in the field of analysis of drugs is due to their simplicity, low cost, and relatively short analysis time when compared with the other techniques. Electrochemical methods have proved to be very sensitive for the determination of organic molecules, including drugs and related molecules in pharmaceutical dosage forms and biological fluids [11–15]. Carbon electrodes, especially glassy carbon electrodes (GCE), are widely used
Transcript of Research Article Square Wave Voltammetric...
Hindawi Publishing CorporationInternational Journal of ElectrochemistryVolume 2013 Article ID 627854 8 pageshttpdxdoiorg1011552013627854
Research ArticleSquare Wave Voltammetric Determination of2-Thiouracil in Pharmaceuticals and Real Samples UsingGlassy Carbon Electrode
Naveen M Gokavi Vijay P Pattar Atmanand M Bagoji and Sharanappa T Nandibewoor
P G Department of Studies in Chemistry Karnatak University Dharwad 580003 India
Correspondence should be addressed to Sharanappa T Nandibewoor stnandibewooryahoocom
Received 19 September 2013 Revised 19 November 2013 Accepted 3 December 2013
Academic Editor Marıa Isabel Pividori
Copyright copy 2013 Naveen M Gokavi et al This is an open access article distributed under the Creative Commons AttributionLicense which permits unrestricted use distribution and reproduction in any medium provided the original work is properlycited
A simple and rapid method was developed using cyclic and square wave voltammetric techniques for the determination of trace-level sulfur containing compound 2-thiouracil at a glassy carbon electrode 2-thiouracil produced two anodic peaks at 0334Vand 1421 V and a cathodic peak at minus0534VThe square wave voltammetry of 2-thiouracil gave a good linear response in the rangeof 1ndash20 120583M with a detection limit of 016120583M and quantification limit of 053 120583M (00679120583gg) which is in good agreement asper IUPAC definition of trace component analysis (100 120583gg) The obtained recoveries range from 9810 to 1021 The proposedmethod was used successfully for its quantitative determination in pharmaceutical formulations and urine as real samples
1 Introduction
In order to meet the growing demands for the new drugs(less costly quite effective and with minimum side effects)to fight against diseases newer drugs are being pushed intothe market at a greater extent that it has become difficult tokeep abreast of their merits and demerits so a strict controlon the quality of the drugs and their therapeutic actionsbecome important Hence the pharmaceutical analysis playsa pivotal role in quality assurance Thiouracil refers bothto a specific molecule consisting of a sulfated uracil and afamily of molecules based upon the structure The substanceis historically relevant in the preparation of antithyroid drugSulfhydryl compounds are known to undergo electrochem-ical oxidation at solid electrodes but their oxidation occursat relatively high potentials [1 2] It was characterized forthe electrocatalytic oxidation of sulfhydryl compounds 2-thiouracil (Scheme 1) and its derivatives also act as selectiveinhibitors of nitric oxide synthase (NOS) [3] The adminis-tration of 2-thiouracil in chicken has been found to causeincrease in total protein content and decrease inDNAcontent[4] Results of some derivatives of 2-thiouracil such as propy-lthiouracil which was used as antithyroid drug produced
thyroid cancers in human and in some animals such asmice rats and hamsters [5] Several methods have beenreported for the determination of 2-thiouracil in complexphysiological samples such as liquid chromatography coupledwith electrochemical detection [6] and spectral studies [7]However these methods suffer from some disadvantagessuch as high cost long analysis time sample pretreatmentlow sensitivity and selectivity which make them unsuitablefor routine analysis In most of the chemical oxidationsof 2-thiouracil SndashS linked dimer is obtained as the majorproduct [8ndash10] However electrochemical oxidation studiesof 2-thiouracil has not attracted much attention Hence itwas considered interesting to study electrochemical oxidationof 2-thiouracil at glassy carbon electrode using square wavevoltammetry
The advance in experimental technique in the field ofanalysis of drugs is due to their simplicity low cost andrelatively short analysis time when compared with the othertechniques Electrochemical methods have proved to bevery sensitive for the determination of organic moleculesincluding drugs and related molecules in pharmaceuticaldosage forms and biological fluids [11ndash15] Carbon electrodesespecially glassy carbon electrodes (GCE) are widely used
2 International Journal of Electrochemistry
O
NH
SNH
OH
N
N SH
Scheme 1 Chemical structure of 2-thiouracil
in the electrochemical investigations because of their lowbackground current wide potential windows chemical inert-ness low cost and suitability for detection of various organicand biological compounds To our knowledge voltammet-ric determination of 2-thiouracil using GCE has not beenreported so farThe objective of the present work is to developa convenient and sensitive method for the determination of2-thiouracil Hence we report the electrochemical behaviourof 2-thiouracil and its determination at GCE using squarewave and cyclic voltammetry techniques It was furthersuccessfully applied for the sensitive and selective determina-tion of 2-thiouracil in pharmaceutical formulations and realsamples
2 Experimental
21 Materials and Reagents The powdered form of 2-thiouracil was obtained fromSigmaAldrich andusedwithoutfurther purification A stock solution (1 times 10minus3M) of 2-thiouracil was prepared in millipore water The phosphatebuffers from pH 3ndash104 were prepared in millipore water asdescribed by Christian and Purdy [16] All other reagentsused were of analytical or reagent grade and their solutionswere prepared with millipore water
22 Instrumentation Electrochemical measurements werecarried out on a CHI 630D electrochemical analyzer (CHInstruments Inc USA) The voltammetric measurementswere carried out in a 10mL single compartment three-electrode glass cell with AgAgCl as a reference electrodea platinum wire as counter electrode and a 3mm diameterglassy carbon electrode (GCE) as the working electrode Allthe potentials are given against the AgAgCl (3MKCl) Allexperiments were carried out at an ambient temperature of25∘C plusmn 01∘C The pH measurements were performed withElico LI120 pH meter (Elico Ltd India)
At different scan rates the area of the electrode was cal-culated using 10mM K
3
Fe(CN)6
as a probe For a reversibleprocess the Randles-Sevcik formula has been used [17]
119894pa = (269 times 105
) 119899
32
119860119863
12
0
119862
0
120592
12
(1)
where 119894pa refers to the anodic peak current 119899 is the numberof electrons transferred119860 is the surface area of the electrode119863
0
is diffusion coefficient 120592 is the scan rate and 1198620
is theconcentration of K
3
Fe(CN)6
For 10mMK3
Fe(CN)6
in 01MKCl electrolyte 119899 = 1 and 119863
0
= 76 times 10
minus6 cm2sminus1 [17] then
from the slope of the plot of 119894pa versus 12059212 relation the surface
area of electrode was calculated In our experiment the slopeobtained was 259times10minus6 and the surface area of glassy carbonelectrode was calculated to be 0035 cm2
23 Analytical Procedure The GCE was carefully polishedusing 03120583m Al
2
O3
slurry on a polishing cloth before eachexperiment After polishing the electrode was rinsed thor-oughly with water After this mechanical treatment the GCEwas placed in buffer solution and various voltammogrammswere recorded until a steady state baseline voltammogramwas obtained
The GCE was first activated in phosphate buffer (pH 30)by cyclic voltammetric sweeps between minus12 and 20V untilstable cyclic voltammograms were obtained Then electrodeswere transferred into another 10mL of phosphate buffer(pH 30) containing proper amount of 2-thiouracil Afteraccumulating for 10 s at open circuit under stirring andfollowing quiet for 10 s potential scan was initiated and cyclicvoltammograms were recorded between minus12 and 20V witha scan rate of 50mVsminus1 All measurements were carried outat room temperature of 25 plusmn 01∘C
3 Results and Discussion
31 Cyclic Voltammetric Behavior of 2-Thiouracil In orderto understand the electrochemical behaviour at the glassycarbon electrode cyclic voltammetry was carried out with2-thiouracil between pH 30 and 104 of phosphate bufferwhich produced two well-defined oxidation peaks and onereduction peak The cyclic voltammograms of 2-thiouracil atpH 42 in phosphate buffer were as shown in Figure 1 Theblank solution without 2-thiouracil was shown by curve (b)and anodic peaks corresponding to 2-thiouracil oxidationappeared at 0334V (peak A) and 1421 V (peak B) and acathodic peak at minus0534V (peak C) as shown in curve (a)
It is shown that the reduction peak was observed in thereverse scan suggesting that the electrochemical reactionwasa quasireversible process [19] Nevertheless it was found thatthe oxidation peak current of 2-thiouracil showed a remark-able decrease during the successive cyclic voltammetricsweeps After every sweep the peak current decreased greatlyand finally remained unchanged This phenomenon may beattributed to the consumption of adsorbed 2-thiouracil onthe electrode surface or due to the fact that the adsorption ofoxidative product occurs at the electrode surface Thereforethe voltammograms corresponding to the first cycle and peakB were generally recorded since peak B was more intensethan A
32 Influence of pH The electrochemical oxidation of 2-thiouracil was studied with different supporting electro-lytes such as Britton-Robinson buffer and phosphate bufferWithin the range of pH 30ndash104 the phosphate buffer gavethe good results as compared to other supporting electrolytes
International Journal of Electrochemistry 3
minus12 minus08 minus04 0 04 08 12 16 20
50
40
30
20
10
0
minus10
minus20
minus30
minus40
minus50
minus60
minus70
minus80
Potential (V)
AB
C
(a)(b)
Curr
ent1
eminus4
(A)
Figure 1 Cyclic voltammogram obtained for 1mM 2-thiouracil onglassy carbon electrode in pH 42 02M buffer (a) 2-thiouracil and(b) blank run without 2-thiouracil at 120592 = 50mVsminus1 (A and B areoxidation peaks whereas C is reduction peak)
(a)
(g)
minus12 minus08 minus04 0 04 08 12 16 20
50
40
30
20
10
0
minus10
minus20
minus30
minus40
minus50
Potential (V)
Curr
ent1
eminus4
(A)
Figure 2 Influence of pH on the shape of the peaks in phosphatebuffer solution at (a) pH 42 (b) pH 30 (c) pH 50 (d) pH 70 (e)pH 80 (f) pH 92 and (g) pH 104 with potential scan rate 50mVsminus1
Hence phosphate buffers were taken as a supporting elec-trolyte With increasing the pH of the buffer solution thepeak potential shifted to less positive values as shown inFigure 2
The plot of 119864119901
versus pH (Figure 3(a)) shows that thepeak potential is pH dependent The variation of peakcurrent with pH is shown in Figure 3(b) Initially the peakcurrent increased from pH 3 to 42 and then decreased frompH 42 to 104 The voltammetric response was markedlydependent on pH From the experimental results (Figure 2)it is observed that highest peak current and better shape ofthe voltammogram was observed at pH 42 suggesting thatpH is optimal pH value From the plot of current versuspH (Figure 3(b)) it is evident that at pH values higher than10 the half peak potential is rather constant indicating thatin solutions with pH greater than 10 the process is not pHdependent It can be concluded that 2-thiouracil in bufferedsolutions with pH greater than 10 exist mainly as thiolateanions and therefore their equilibrium concentrations do not
0 5 10 15
pH
0
02
04
06
08
1
12
14
16
A
B
Ep
(V)
(a)
pH2 4 6 8 10
0
05
1
15
2
25
3
35
4
45
A
B
1eminus4
(A)
i p
(b)
Figure 3 (a) Influence of pH on the peak potential of 2-thiouracilfor peaks A and B (b) Variation of peak currents of peaks A and Bwith pH
vary by increasing the pH of solution Hence pH variation isrestricted to 104
33 Influence of Scan Rate Useful information involvingelectrochemical mechanism usually can be acquired from therelationship between peak current and scan rate Thereforethe electrochemical behavior of 2-thiouracil at different scanrates from 50 to 250mVsminus1 (Figure 4) was also studiedFrom this we observed that by increasing the scan ratethe peak potential of B was shifted to more positive valuesSimultaneously the width at half-height of peak B increasedIt is suggested that this corresponds to the oxidation of 2-thiouracil dimers formed at the GCE surface The formationof such kind of dimers is well documented in the literature [7](Scheme 2) but they can only be observed when high scanrates are used probably because they have short life time Atthe same time the cathodic peak C is displaced tomore nega-tive values whereas its current increases with the scan rate
4 International Journal of Electrochemistry
minus12 minus08 minus04 0 04 08 12 16 20
50
40
30
20
10
0
minus10
minus20
minus30
minus40
minus50
minus60
Potential (V)
(a)
(b)
(c)(d)
(e)
Curr
ent1
eminus4
(A)
Figure 4 Cyclic voltammograms of 10mM 2-thiouracil on GCEwith different scan rates at (a) 50 (b) 100 (c) 150 (d) 200 and (e)250mVsminus1
There is a good linear relationship between peak currentand scan rate The equations are
119894
119901
(10
minus4 A) = 1606120592 (Vsminus1) + 0253 119903 = 0998
119894
119901
(10
minus4 A) = 2014120592 (Vsminus1) + 0064 119903 = 0997(2)
for peaks A and B respectively as shown in Figure 5(a) Inaddition there was a linear relation between log 119894
119901
and log 120592corresponding to the following equation
log 119894119901
(10
minus4 A) = 0988 log 120592 (Vsminus1) + 1304 119903 = 0998
log 119894119901
(10
minus4 A) = 0892 log 120592 (Vsminus1) + 1165 119903 = 0999(3)
for peaks A and B respectively (Figure 5(b)) The slope of0988 and 0892 is close to the theoretically expected valueof 1 for an adsorption controlled process [20]
The peak potential shifted to more positive values withincreasing the scan rates The linear relationship betweenpeak potential and logarithm of scan rate can be expressedas
119864
119901
(V) = 0126 log 120592 + 0487 119903 = 0901
119864
119901
(V) = 0261 log 120592 + 1598 119903 = 0986(4)
for the peaks A and B respectively (Figure 5(c))Figure 4 depicts a family of CV recorded in the system
at different potential scan rates From this figure it waspossible to gather information shown in Table 1 regardingthe influence of the potential scan rate on the voltammetricparameters of the system From the variation of Δ119864 valueswith the potential scan rate shown in Table 1 one mayconclude in this case that the 2-thiouracil electrochemicaloxidation atGCE is a quasireversiblemass transfer-controlledprocess see Figures 5(a) and 5(d) However the behavior ofthe ratio |119894pc119894pa| for both the peaks (A and B) may indicate
the presence of a coupled chemical reaction [21] On the basisof similar voltammetric behaviour observed in the presentstudy the same mechanism may be proposed as given in [7](Scheme 2)
34 Calibration Curve In order to develop a rapid and sensi-tive voltammetric method for determining the 2-thiouracilwe adopted the square wave voltammetric (SWV) modebecause the peaks were sharper and better defined at lowerconcentration of 2-thiouracil than those obtained by cyclicvoltammetry with low background current resulting inimproved resolution According to the obtained results it waspossible to apply this technique to the quantitative analysisof 2-thiouracil The phosphate buffer solution of pH 42 wasselected as the supporting electrolyte for the quantificationof 2-thiouracil as it gave maximum peak current at pH42 The peak at about 105V in SWV was considered forthe analysis Square wave voltammograms obtained withincreasing amount of 2-thiouracil showed that the peakcurrent increased linearly with increasing concentration asshown in Figures 6(a) and 6(b)
Using the optimum conditions described above linearcalibration curves were obtained for 2-thiouracil in the rangeof 1 to 200120583MThe linear equation was
119894
119901
(120583A) = 0166119862 (120583M) + 7925 (119903 = 0995) (5)
Deviation from linearity was observed for more concen-trated solutions due to the adsorption of oxidation producton the electrode surface It was also observed that thepeak potential (119864
119901
) and half peak potential (119864119901
2) wereshifted towards more positive value suggesting that productundergoes adsorption at the surface of GCE Related statis-tical data of the calibration curve was obtained from fivedifferent calibration curvesThe limit of detection (LOD) andquantification (LOQ)were 016120583Mand053 120583M respectivelyThe LOD and LOQ were calculated using the followingequations
LOD = 3119904119898
LOQ = 10119904119898
(6)
where 119904 is the standard deviation of the peak currents of theblank (five runs) and 119898 is the slope of the calibration curveComparison of earlier methods with the present methodshowed the present method was better for the determinationof 2-thiouracil (Table 2)
35 Stability and Reproducibility In order to study the stabil-ity and reproducibility of the electrode a 10120583M 2-thiouracilsolution was measured with the same electrode (renewedevery time) for every several hours within day the RSDof the peak current was 069 (number of measurements= 5) As to the between-day reproducibility it was similarto that of within a day if the temperature was kept almostunchangedwhich could be attributed to the excellent stabilityand reproducibility of GCE
36 Effect of Interferents For the analytical applications ofthe proposedmethod the effects of potential interferents that
International Journal of Electrochemistry 5
O
NH
SNH
2 2 2
SHN
OH
N
SminusN N N
OH OH OH
N N N
S S
minus2eminus minus2H+
Scheme 2 Proposed mechanism
0 01 02 03
0
1
2
3
4
5
6
A
B
1eminus4
(A)
i p
120592 (Vsminus1)
(a)
log120592 (Vsminus1)0
0
02
04
06
08
1
12
minus15 minus1 minus05
A
B
Logi
p(A
)
(b)
log120592 (Vsminus1)00
02
04
06
08
1
16
14
12
minus15 minus1 minus05
A
B
Ep
(V)
(c)
A
B
02 03 04 05 06
0
1
2
3
4
5
6
120592 12 (Vsminus1)12
i p1eminus4
(A)
(d)
Figure 5 (a) Dependence of the oxidation peak current of peaks A and B on the scan rate (b) Dependence of the logarithm of peak currenton logarithm of scan rate for peaks A and B (c) Relationship between peak potential and logarithm of scan rate for the peaks A and B (d)Relationship between peak current of peaks A and B on the square root of scan rate
Table 1 Variation of the voltammetric parameters as a function of the potential scan rate (120592) corresponding to the CVs shown in Figure 4
120592
(mVsminus1)119864paA(mV)
119864paB(mV)
119864pc(mV)
Δ119864A(119864paA minus 119864pc)
(mV)
Δ119864B(119864paB minus 119864pc)
(mV)
119894paA10minus4 (A)
119894paB10minus4 (A)
119894pc
10minus4 (A)
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
119894pc
119894paA
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
119894pc
119894paB
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
50 326 1256 minus501 827 1757 minus1001 minus1035 1241 1239 1199100 362 1343 minus595 957 1938 minus1920 minus2076 2383 1241 1147150 376 1379 minus614 989 1993 minus2691 minus3201 3125 1161 09762200 385 1403 minus646 103 2049 minus3456 minus4012 3813 1103 09503250 428 1451 minus702 113 2152 minus4251 minus5102 4262 1002 08353
6 International Journal of Electrochemistry
Potential (V)080 085 090 095 100 105 110 115 120
minus02
minus03
minus04
minus05
minus06
minus07
minus08
minus09
minus10
minus11
minus12
(a)
(h)
Curr
ent1
eminus5
(A)
(a)
[2-TU] (120583M)0 10 20 30
minus80
minus85
minus90
minus95
minus100
minus105
minus110
Curr
ent1
eminus6
(A)
(b)
Figure 6 (a) Square wave voltammograms of GCE in 2-thiouracilsolution at different concentrations at (a) 1 (b) 3 (c) 5 (d) 7 (e) 9(f) 10 (g) 15 and (h) 20120583M and (b) plot of the peak current againstconcentration of 2-thiouracil
Table 2 Comparison of some methods for the determination of 2-thiouracil with the proposed method
Analytical method Linearity range(mM)
Detection limit(120583M) Ref
LiquidChromatography (05ndash40) (043) [6]
Carbon-pasteelectrode modifiedwith CoPc
(07ndash800) (40) [18]
Glassy carbonelectrode (0001ndash0015) (016) This work
are likely to be in biological samples were evaluated underthe optimum experimental conditions Square wave voltam-metric experiments were carried out for 10120583M 2-thiouracilin the presence of 10mM of each of the interferents Theexperimental results (Table 3) showed that thousand-fold
Table 3 Influence of potential interferents on the voltammetricresponse of 10 120583M 2-thiouracil
Interferents Concentration (mM) Signal change ()Citric acid 10395 018Dextrose 10320 093D-glucose 10850 minus44Gum acacia 09916 50Oxalic acid 10157 26Starch 10162 25Sucrose 10719 minus31
Table 4 Results of the assay and the recovery test of 2TU inpharmaceutical preparations using square wave voltammetry
Propylthiouracil tabletLabeled claim (mg) 500Amount found (mg)a 490RSD () 065Bias () minus20Added (mg) 500Found (mg)a 492Recovered () 984RSD () 038Calculated 119865 124Calculated 119905 216Bias () minus16aMean average of five determinations
excess of glucose starch sucrose dextrose gum acacia citricacid and oxalic acid did not interfere with the voltammetricsignal of 2-thiouracilTherefore the proposedmethod can beused as a selective method
37 Tablet Analysis and Recovery Test In order toevaluate the applicability of the proposed method thecommercial medicinal sample containing 2-thiouracilfrom Propylthiouracil India was studied The tablets weregrounded to powder dissolved in water and then furtherdiluted so that 2-thiouracil concentration falls in the rangeof calibration plot Square wave voltammograms werethen recorded under exactly identical conditions that wereemployed while recording square wave voltammogramsfor plotting calibration plot It was found that 2-thiouracilconcentration determined for various tablets using thismethod are in good agreement with the reported valuesThe values of experimentally determined 2-thiouraciland its amounts agreed reasonably well (Table 4)The typical square wave voltammograms for the 6-propylthiouracil solution at GCE are shown in Figure 7(a)
38 Detection of 2-Thiouracil in Urine Samples The appli-cability of the SWV to the determination of 2-thiouracilin spiked urine was also investigated The recoveries fromurine were measured by spiking drug-free urine with knownamounts of 2-thiouracil The urine samples were diluted
International Journal of Electrochemistry 7
080 090 100 110 120 130 140
(i)(ii)
(iii)
minus10
minus20
minus30
minus40
minus50
minus60
minus70
minus80
minus90
Potential (V)
Curr
ent1
eminus6
(A)
(a)
080 085 090 095 100 105 110 115 120minus30
minus40
minus50
minus60
minus70
minus80
minus90
minus100
(i)
(ii)
(iii)
Potential (V)
Curr
ent1
eminus6
(A)
(b)
Figure 7 Typical square wave voltammograms on GCE in (a) 6-propylthiouracil solution at different concentrations (i) 2 120583M (ii) 4 120583M and(iii) 6120583M in tablet solutions and (b) 2-thiouracil solution at different concentrations (i) 2 120583M (ii) 4120583M and (iii) 6120583M in urine samples
Table 5 Determination of 2-thiouracil in urine samples
Urine Spiked (120583M) Detecteda (120583M) Bias () Recovery () SD plusmn RSD ()Sample 1 2 2062 31 1031 00301 plusmn 039
Sample 2 4 4040 10 1010 00222 plusmn 055
Sample 3 6 5909 minus15 9848 00099 plusmn 017
Sample 4 8 7813 minus23 9766 00207 plusmn 027
aMean average of five determinations
100 times with the phosphate buffer solution before analysiswithout further pretreatment A quantitative determinationcan be carried out by adding the standard solution of 2-thiouracil into the detection system of urine sample Thecalibration graph was used for the determination of spiked2-thiouracil in urine samples The detection results of foururine samples obtained are listed in Table 5 The recoverydetermined was in the range from 976 to 1031 and theRSD was 034 Thus satisfactory recoveries of the analytefrom the real samples and a good agreement between theconcentration ranges studied and the real ranges encounteredin the urine samples when treated with the drug make thedeveloped method applicable in clinical analysis The typicalsquare wave voltammograms for the 2-thiouracil solution atGCE are shown in Figure 7(b)
4 Conclusion
The main aim of drug analysis is to contribute to theimprovement of drug safety Due to the poor selectivity ofthe titrimetric and spectrophotometric assay methods andthe insufficient precision of the selective HPLC methodnone of these methods can be considered to fulfill thisrequirement Nowadays due to advancement in the field ofelectrochemistry some other types of electrodes are used toget high sensitivity and selectivity of drugs A glassy carbonelectrode was used for the first time for the oxidation of2-thiouracil in phosphate buffer solution A suitable mech-anism was proposed This proposed method can be used
for voltammetric determination of selected analyte as low as016 120583M with good reproducibility The method offered theadvantages of accuracy and time saving as well as simplicityof reagents and apparatus In addition the results obtainedare successfully applied in pharmaceutical formulations andspiked urine samples The proposed method is suitablefor quality control laboratories as well as pharmacokineticstudies with satisfactory result
References
[1] J P Hart Electroanalysis of Biologically Important CompoundsEllis Horwood Chichester UK 1990
[2] J P Hart and I C Hartley ldquoVoltammetric and amperomet-ric studies of thiocholine at a screen-printed carbon elec-trode chemically modified with cobalt phthalocyanine studiestowards a pesticide sensorrdquoThe Analyst vol 119 no 2 pp 259ndash263 1994
[3] A Palumbo M DrsquoIschia and F A Cioffi ldquo2-Thiouracil is aselective inhibitor of neuronal nitric oxide synthase antago-nising tetrahydrobiopterin-dependent enzyme activation anddimerisationrdquo FEBS Letters vol 485 no 2-3 pp 109ndash112 2000
[4] I Roman and R Giurgea ldquoThyroxin and thiouracyl influenceupon some biochemical parameters in chicken thymusesrdquoRomanian Journal of Physiology vol 36 no 1-2 pp 97ndash101 1999
[5] B M Dobyns G E Sheline and J B Workman ldquoMalignantand benign neoplasms of the thyroid in patients treated forhyperthyroidism a report of the cooperative thyrotoxicosistherapy Follow up studyrdquo Journal of Clinical Endocrinology andMetabolism vol 38 no 6 pp 976ndash998 1974
8 International Journal of Electrochemistry
[6] C Anton and C Cristian ldquoDetermination of 2-thiouracyl incomplex samples By liquid chromatography with electrochemi-cal detectionrdquoRomanianBiotechnological Letters vol 7 pp 847ndash854 2002
[7] R N Goyal U P Singh and A A Abdullah ldquoElectrochemicaloxidation of 2-thiouracil at pyrolytic graphite electroderdquo Bio-electrochemistry vol 67 no 1 pp 7ndash13 2005
[8] M Hepel and R A Osteryoung ldquoElectrochemical behavior of2-thiouracil on silver electrodesrdquo Journal of ElectroanalyticalChemistry vol 160 no 1-2 pp 217ndash231 1984
[9] P Swamy and N Vaz ldquoRuthenium(III)- and osmium(VIII)-catalyzed oxidation of 2-thiouracil by bromamine-B in acidand alkaline media a kinetic andmechanistic studyrdquo TransitionMetal Chemistry vol 28 no 4 pp 409ndash417 2003
[10] S Shahrokhian andAHamzehloei ldquoElectrochemical oxidationof catechol in the presence of 2-thiouracil application toelectro-organic synthesisrdquo Electrochemistry Communicationsvol 5 no 8 pp 706ndash710 2003
[11] B Uslu and S A Ozkan ldquoElectrochemical characterisationof nefazodone hydrochloride and voltammetric determinationof the drug in pharmaceuticals and human serumrdquo AnalyticaChimica Acta vol 462 no 1 pp 49ndash57 2002
[12] J-M Kauffmann M P Prete J-C Vire and G J PatriarcheldquoVoltammetry of pharmaceuticals using different types of mod-ified electrodesrdquo Fresenius Zeitschrift fur Analytische Chemievol 321 no 2 pp 172ndash176 1985
[13] F Belal H Abdine and N Zoman ldquoVoltammetric determina-tion of nilvadipine in dosage forms and spiked human urinerdquoJournal of Pharmaceutical and Biomedical Analysis vol 26 no4 pp 585ndash592 2001
[14] P Zuman ldquoCurrent status of polarography and voltammetry inanalytical chemistryrdquo Analytical Letters vol 33 no 2 pp 163ndash174 2000
[15] T B Demircigil S AOzkanO Coruh and S Yilmaz ldquoElectro-chemical behavior of formoterol fumarate and its determinationin capsules for inhalation and human serum using differential-pulse and square-wave voltammetryrdquoElectroanalysis vol 14 pp122ndash127 2002
[16] G D Christian and W C Purdy ldquoThe residual current inorthophosphate mediumrdquo Journal of Electroanalytical Chem-istry vol 3 no 6 pp 363ndash367 1962
[17] B Rezaei and S Damiri ldquoVoltammetric behavior of multi-walled carbon nanotubes modified electrode-hexacyanofer-rate(II) electrocatalyst system as a sensor for determination ofcaptoprilrdquo Sensors and Actuators B vol 134 no 1 pp 324ndash3312008
[18] S ShahrokhianAHamzehloei AThaghani and S RMousavildquoElectrocatalytic oxidation of 2-thiouracil and 2-thiobarbituricacid at a carbon-paste electrode modified with cobalt phthalo-cyaninerdquo Electroanalysis vol 16 no 11 pp 915ndash921 2004
[19] B Eswarappa B S Sherigara and B E Kumaraswamy ldquoElec-trochemical investigation of benzelidene benzyl hydrazide andits derivative schiff bases at glassy carbon electroderdquo Bulletin ofElectrochemistry vol 20 no 1 pp 1ndash6 2004
[20] D K Gosser Cyclic Voltammetry Simulation and Analysis ofReaction Mechansims Vancouver Coastal Health New YorkNY USA 1993
[21] S Corona-Avendano G Alarcon-Angeles M T Ramırez-SilvaG Rosquete-PinaMRomero-Romo andM Palomar-Pardave
ldquoOn the electrochemistry of dopamine in aqueous solution PartI the role of [SDS] on the voltammetric behavior of dopamineon a carbon paste electroderdquo Journal of Electroanalytical Chem-istry vol 609 no 1 pp 17ndash26 2007
Submit your manuscripts athttpwwwhindawicom
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Inorganic ChemistryInternational Journal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
International Journal ofPhotoenergy
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Carbohydrate Chemistry
International Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Advances in
Physical Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom
Analytical Methods in Chemistry
Journal of
Volume 2014
Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
SpectroscopyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Medicinal ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Chromatography Research International
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Applied ChemistryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Theoretical ChemistryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Spectroscopy
Analytical ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Quantum Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Organic Chemistry International
ElectrochemistryInternational Journal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
CatalystsJournal of
2 International Journal of Electrochemistry
O
NH
SNH
OH
N
N SH
Scheme 1 Chemical structure of 2-thiouracil
in the electrochemical investigations because of their lowbackground current wide potential windows chemical inert-ness low cost and suitability for detection of various organicand biological compounds To our knowledge voltammet-ric determination of 2-thiouracil using GCE has not beenreported so farThe objective of the present work is to developa convenient and sensitive method for the determination of2-thiouracil Hence we report the electrochemical behaviourof 2-thiouracil and its determination at GCE using squarewave and cyclic voltammetry techniques It was furthersuccessfully applied for the sensitive and selective determina-tion of 2-thiouracil in pharmaceutical formulations and realsamples
2 Experimental
21 Materials and Reagents The powdered form of 2-thiouracil was obtained fromSigmaAldrich andusedwithoutfurther purification A stock solution (1 times 10minus3M) of 2-thiouracil was prepared in millipore water The phosphatebuffers from pH 3ndash104 were prepared in millipore water asdescribed by Christian and Purdy [16] All other reagentsused were of analytical or reagent grade and their solutionswere prepared with millipore water
22 Instrumentation Electrochemical measurements werecarried out on a CHI 630D electrochemical analyzer (CHInstruments Inc USA) The voltammetric measurementswere carried out in a 10mL single compartment three-electrode glass cell with AgAgCl as a reference electrodea platinum wire as counter electrode and a 3mm diameterglassy carbon electrode (GCE) as the working electrode Allthe potentials are given against the AgAgCl (3MKCl) Allexperiments were carried out at an ambient temperature of25∘C plusmn 01∘C The pH measurements were performed withElico LI120 pH meter (Elico Ltd India)
At different scan rates the area of the electrode was cal-culated using 10mM K
3
Fe(CN)6
as a probe For a reversibleprocess the Randles-Sevcik formula has been used [17]
119894pa = (269 times 105
) 119899
32
119860119863
12
0
119862
0
120592
12
(1)
where 119894pa refers to the anodic peak current 119899 is the numberof electrons transferred119860 is the surface area of the electrode119863
0
is diffusion coefficient 120592 is the scan rate and 1198620
is theconcentration of K
3
Fe(CN)6
For 10mMK3
Fe(CN)6
in 01MKCl electrolyte 119899 = 1 and 119863
0
= 76 times 10
minus6 cm2sminus1 [17] then
from the slope of the plot of 119894pa versus 12059212 relation the surface
area of electrode was calculated In our experiment the slopeobtained was 259times10minus6 and the surface area of glassy carbonelectrode was calculated to be 0035 cm2
23 Analytical Procedure The GCE was carefully polishedusing 03120583m Al
2
O3
slurry on a polishing cloth before eachexperiment After polishing the electrode was rinsed thor-oughly with water After this mechanical treatment the GCEwas placed in buffer solution and various voltammogrammswere recorded until a steady state baseline voltammogramwas obtained
The GCE was first activated in phosphate buffer (pH 30)by cyclic voltammetric sweeps between minus12 and 20V untilstable cyclic voltammograms were obtained Then electrodeswere transferred into another 10mL of phosphate buffer(pH 30) containing proper amount of 2-thiouracil Afteraccumulating for 10 s at open circuit under stirring andfollowing quiet for 10 s potential scan was initiated and cyclicvoltammograms were recorded between minus12 and 20V witha scan rate of 50mVsminus1 All measurements were carried outat room temperature of 25 plusmn 01∘C
3 Results and Discussion
31 Cyclic Voltammetric Behavior of 2-Thiouracil In orderto understand the electrochemical behaviour at the glassycarbon electrode cyclic voltammetry was carried out with2-thiouracil between pH 30 and 104 of phosphate bufferwhich produced two well-defined oxidation peaks and onereduction peak The cyclic voltammograms of 2-thiouracil atpH 42 in phosphate buffer were as shown in Figure 1 Theblank solution without 2-thiouracil was shown by curve (b)and anodic peaks corresponding to 2-thiouracil oxidationappeared at 0334V (peak A) and 1421 V (peak B) and acathodic peak at minus0534V (peak C) as shown in curve (a)
It is shown that the reduction peak was observed in thereverse scan suggesting that the electrochemical reactionwasa quasireversible process [19] Nevertheless it was found thatthe oxidation peak current of 2-thiouracil showed a remark-able decrease during the successive cyclic voltammetricsweeps After every sweep the peak current decreased greatlyand finally remained unchanged This phenomenon may beattributed to the consumption of adsorbed 2-thiouracil onthe electrode surface or due to the fact that the adsorption ofoxidative product occurs at the electrode surface Thereforethe voltammograms corresponding to the first cycle and peakB were generally recorded since peak B was more intensethan A
32 Influence of pH The electrochemical oxidation of 2-thiouracil was studied with different supporting electro-lytes such as Britton-Robinson buffer and phosphate bufferWithin the range of pH 30ndash104 the phosphate buffer gavethe good results as compared to other supporting electrolytes
International Journal of Electrochemistry 3
minus12 minus08 minus04 0 04 08 12 16 20
50
40
30
20
10
0
minus10
minus20
minus30
minus40
minus50
minus60
minus70
minus80
Potential (V)
AB
C
(a)(b)
Curr
ent1
eminus4
(A)
Figure 1 Cyclic voltammogram obtained for 1mM 2-thiouracil onglassy carbon electrode in pH 42 02M buffer (a) 2-thiouracil and(b) blank run without 2-thiouracil at 120592 = 50mVsminus1 (A and B areoxidation peaks whereas C is reduction peak)
(a)
(g)
minus12 minus08 minus04 0 04 08 12 16 20
50
40
30
20
10
0
minus10
minus20
minus30
minus40
minus50
Potential (V)
Curr
ent1
eminus4
(A)
Figure 2 Influence of pH on the shape of the peaks in phosphatebuffer solution at (a) pH 42 (b) pH 30 (c) pH 50 (d) pH 70 (e)pH 80 (f) pH 92 and (g) pH 104 with potential scan rate 50mVsminus1
Hence phosphate buffers were taken as a supporting elec-trolyte With increasing the pH of the buffer solution thepeak potential shifted to less positive values as shown inFigure 2
The plot of 119864119901
versus pH (Figure 3(a)) shows that thepeak potential is pH dependent The variation of peakcurrent with pH is shown in Figure 3(b) Initially the peakcurrent increased from pH 3 to 42 and then decreased frompH 42 to 104 The voltammetric response was markedlydependent on pH From the experimental results (Figure 2)it is observed that highest peak current and better shape ofthe voltammogram was observed at pH 42 suggesting thatpH is optimal pH value From the plot of current versuspH (Figure 3(b)) it is evident that at pH values higher than10 the half peak potential is rather constant indicating thatin solutions with pH greater than 10 the process is not pHdependent It can be concluded that 2-thiouracil in bufferedsolutions with pH greater than 10 exist mainly as thiolateanions and therefore their equilibrium concentrations do not
0 5 10 15
pH
0
02
04
06
08
1
12
14
16
A
B
Ep
(V)
(a)
pH2 4 6 8 10
0
05
1
15
2
25
3
35
4
45
A
B
1eminus4
(A)
i p
(b)
Figure 3 (a) Influence of pH on the peak potential of 2-thiouracilfor peaks A and B (b) Variation of peak currents of peaks A and Bwith pH
vary by increasing the pH of solution Hence pH variation isrestricted to 104
33 Influence of Scan Rate Useful information involvingelectrochemical mechanism usually can be acquired from therelationship between peak current and scan rate Thereforethe electrochemical behavior of 2-thiouracil at different scanrates from 50 to 250mVsminus1 (Figure 4) was also studiedFrom this we observed that by increasing the scan ratethe peak potential of B was shifted to more positive valuesSimultaneously the width at half-height of peak B increasedIt is suggested that this corresponds to the oxidation of 2-thiouracil dimers formed at the GCE surface The formationof such kind of dimers is well documented in the literature [7](Scheme 2) but they can only be observed when high scanrates are used probably because they have short life time Atthe same time the cathodic peak C is displaced tomore nega-tive values whereas its current increases with the scan rate
4 International Journal of Electrochemistry
minus12 minus08 minus04 0 04 08 12 16 20
50
40
30
20
10
0
minus10
minus20
minus30
minus40
minus50
minus60
Potential (V)
(a)
(b)
(c)(d)
(e)
Curr
ent1
eminus4
(A)
Figure 4 Cyclic voltammograms of 10mM 2-thiouracil on GCEwith different scan rates at (a) 50 (b) 100 (c) 150 (d) 200 and (e)250mVsminus1
There is a good linear relationship between peak currentand scan rate The equations are
119894
119901
(10
minus4 A) = 1606120592 (Vsminus1) + 0253 119903 = 0998
119894
119901
(10
minus4 A) = 2014120592 (Vsminus1) + 0064 119903 = 0997(2)
for peaks A and B respectively as shown in Figure 5(a) Inaddition there was a linear relation between log 119894
119901
and log 120592corresponding to the following equation
log 119894119901
(10
minus4 A) = 0988 log 120592 (Vsminus1) + 1304 119903 = 0998
log 119894119901
(10
minus4 A) = 0892 log 120592 (Vsminus1) + 1165 119903 = 0999(3)
for peaks A and B respectively (Figure 5(b)) The slope of0988 and 0892 is close to the theoretically expected valueof 1 for an adsorption controlled process [20]
The peak potential shifted to more positive values withincreasing the scan rates The linear relationship betweenpeak potential and logarithm of scan rate can be expressedas
119864
119901
(V) = 0126 log 120592 + 0487 119903 = 0901
119864
119901
(V) = 0261 log 120592 + 1598 119903 = 0986(4)
for the peaks A and B respectively (Figure 5(c))Figure 4 depicts a family of CV recorded in the system
at different potential scan rates From this figure it waspossible to gather information shown in Table 1 regardingthe influence of the potential scan rate on the voltammetricparameters of the system From the variation of Δ119864 valueswith the potential scan rate shown in Table 1 one mayconclude in this case that the 2-thiouracil electrochemicaloxidation atGCE is a quasireversiblemass transfer-controlledprocess see Figures 5(a) and 5(d) However the behavior ofthe ratio |119894pc119894pa| for both the peaks (A and B) may indicate
the presence of a coupled chemical reaction [21] On the basisof similar voltammetric behaviour observed in the presentstudy the same mechanism may be proposed as given in [7](Scheme 2)
34 Calibration Curve In order to develop a rapid and sensi-tive voltammetric method for determining the 2-thiouracilwe adopted the square wave voltammetric (SWV) modebecause the peaks were sharper and better defined at lowerconcentration of 2-thiouracil than those obtained by cyclicvoltammetry with low background current resulting inimproved resolution According to the obtained results it waspossible to apply this technique to the quantitative analysisof 2-thiouracil The phosphate buffer solution of pH 42 wasselected as the supporting electrolyte for the quantificationof 2-thiouracil as it gave maximum peak current at pH42 The peak at about 105V in SWV was considered forthe analysis Square wave voltammograms obtained withincreasing amount of 2-thiouracil showed that the peakcurrent increased linearly with increasing concentration asshown in Figures 6(a) and 6(b)
Using the optimum conditions described above linearcalibration curves were obtained for 2-thiouracil in the rangeof 1 to 200120583MThe linear equation was
119894
119901
(120583A) = 0166119862 (120583M) + 7925 (119903 = 0995) (5)
Deviation from linearity was observed for more concen-trated solutions due to the adsorption of oxidation producton the electrode surface It was also observed that thepeak potential (119864
119901
) and half peak potential (119864119901
2) wereshifted towards more positive value suggesting that productundergoes adsorption at the surface of GCE Related statis-tical data of the calibration curve was obtained from fivedifferent calibration curvesThe limit of detection (LOD) andquantification (LOQ)were 016120583Mand053 120583M respectivelyThe LOD and LOQ were calculated using the followingequations
LOD = 3119904119898
LOQ = 10119904119898
(6)
where 119904 is the standard deviation of the peak currents of theblank (five runs) and 119898 is the slope of the calibration curveComparison of earlier methods with the present methodshowed the present method was better for the determinationof 2-thiouracil (Table 2)
35 Stability and Reproducibility In order to study the stabil-ity and reproducibility of the electrode a 10120583M 2-thiouracilsolution was measured with the same electrode (renewedevery time) for every several hours within day the RSDof the peak current was 069 (number of measurements= 5) As to the between-day reproducibility it was similarto that of within a day if the temperature was kept almostunchangedwhich could be attributed to the excellent stabilityand reproducibility of GCE
36 Effect of Interferents For the analytical applications ofthe proposedmethod the effects of potential interferents that
International Journal of Electrochemistry 5
O
NH
SNH
2 2 2
SHN
OH
N
SminusN N N
OH OH OH
N N N
S S
minus2eminus minus2H+
Scheme 2 Proposed mechanism
0 01 02 03
0
1
2
3
4
5
6
A
B
1eminus4
(A)
i p
120592 (Vsminus1)
(a)
log120592 (Vsminus1)0
0
02
04
06
08
1
12
minus15 minus1 minus05
A
B
Logi
p(A
)
(b)
log120592 (Vsminus1)00
02
04
06
08
1
16
14
12
minus15 minus1 minus05
A
B
Ep
(V)
(c)
A
B
02 03 04 05 06
0
1
2
3
4
5
6
120592 12 (Vsminus1)12
i p1eminus4
(A)
(d)
Figure 5 (a) Dependence of the oxidation peak current of peaks A and B on the scan rate (b) Dependence of the logarithm of peak currenton logarithm of scan rate for peaks A and B (c) Relationship between peak potential and logarithm of scan rate for the peaks A and B (d)Relationship between peak current of peaks A and B on the square root of scan rate
Table 1 Variation of the voltammetric parameters as a function of the potential scan rate (120592) corresponding to the CVs shown in Figure 4
120592
(mVsminus1)119864paA(mV)
119864paB(mV)
119864pc(mV)
Δ119864A(119864paA minus 119864pc)
(mV)
Δ119864B(119864paB minus 119864pc)
(mV)
119894paA10minus4 (A)
119894paB10minus4 (A)
119894pc
10minus4 (A)
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
119894pc
119894paA
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
119894pc
119894paB
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
50 326 1256 minus501 827 1757 minus1001 minus1035 1241 1239 1199100 362 1343 minus595 957 1938 minus1920 minus2076 2383 1241 1147150 376 1379 minus614 989 1993 minus2691 minus3201 3125 1161 09762200 385 1403 minus646 103 2049 minus3456 minus4012 3813 1103 09503250 428 1451 minus702 113 2152 minus4251 minus5102 4262 1002 08353
6 International Journal of Electrochemistry
Potential (V)080 085 090 095 100 105 110 115 120
minus02
minus03
minus04
minus05
minus06
minus07
minus08
minus09
minus10
minus11
minus12
(a)
(h)
Curr
ent1
eminus5
(A)
(a)
[2-TU] (120583M)0 10 20 30
minus80
minus85
minus90
minus95
minus100
minus105
minus110
Curr
ent1
eminus6
(A)
(b)
Figure 6 (a) Square wave voltammograms of GCE in 2-thiouracilsolution at different concentrations at (a) 1 (b) 3 (c) 5 (d) 7 (e) 9(f) 10 (g) 15 and (h) 20120583M and (b) plot of the peak current againstconcentration of 2-thiouracil
Table 2 Comparison of some methods for the determination of 2-thiouracil with the proposed method
Analytical method Linearity range(mM)
Detection limit(120583M) Ref
LiquidChromatography (05ndash40) (043) [6]
Carbon-pasteelectrode modifiedwith CoPc
(07ndash800) (40) [18]
Glassy carbonelectrode (0001ndash0015) (016) This work
are likely to be in biological samples were evaluated underthe optimum experimental conditions Square wave voltam-metric experiments were carried out for 10120583M 2-thiouracilin the presence of 10mM of each of the interferents Theexperimental results (Table 3) showed that thousand-fold
Table 3 Influence of potential interferents on the voltammetricresponse of 10 120583M 2-thiouracil
Interferents Concentration (mM) Signal change ()Citric acid 10395 018Dextrose 10320 093D-glucose 10850 minus44Gum acacia 09916 50Oxalic acid 10157 26Starch 10162 25Sucrose 10719 minus31
Table 4 Results of the assay and the recovery test of 2TU inpharmaceutical preparations using square wave voltammetry
Propylthiouracil tabletLabeled claim (mg) 500Amount found (mg)a 490RSD () 065Bias () minus20Added (mg) 500Found (mg)a 492Recovered () 984RSD () 038Calculated 119865 124Calculated 119905 216Bias () minus16aMean average of five determinations
excess of glucose starch sucrose dextrose gum acacia citricacid and oxalic acid did not interfere with the voltammetricsignal of 2-thiouracilTherefore the proposedmethod can beused as a selective method
37 Tablet Analysis and Recovery Test In order toevaluate the applicability of the proposed method thecommercial medicinal sample containing 2-thiouracilfrom Propylthiouracil India was studied The tablets weregrounded to powder dissolved in water and then furtherdiluted so that 2-thiouracil concentration falls in the rangeof calibration plot Square wave voltammograms werethen recorded under exactly identical conditions that wereemployed while recording square wave voltammogramsfor plotting calibration plot It was found that 2-thiouracilconcentration determined for various tablets using thismethod are in good agreement with the reported valuesThe values of experimentally determined 2-thiouraciland its amounts agreed reasonably well (Table 4)The typical square wave voltammograms for the 6-propylthiouracil solution at GCE are shown in Figure 7(a)
38 Detection of 2-Thiouracil in Urine Samples The appli-cability of the SWV to the determination of 2-thiouracilin spiked urine was also investigated The recoveries fromurine were measured by spiking drug-free urine with knownamounts of 2-thiouracil The urine samples were diluted
International Journal of Electrochemistry 7
080 090 100 110 120 130 140
(i)(ii)
(iii)
minus10
minus20
minus30
minus40
minus50
minus60
minus70
minus80
minus90
Potential (V)
Curr
ent1
eminus6
(A)
(a)
080 085 090 095 100 105 110 115 120minus30
minus40
minus50
minus60
minus70
minus80
minus90
minus100
(i)
(ii)
(iii)
Potential (V)
Curr
ent1
eminus6
(A)
(b)
Figure 7 Typical square wave voltammograms on GCE in (a) 6-propylthiouracil solution at different concentrations (i) 2 120583M (ii) 4 120583M and(iii) 6120583M in tablet solutions and (b) 2-thiouracil solution at different concentrations (i) 2 120583M (ii) 4120583M and (iii) 6120583M in urine samples
Table 5 Determination of 2-thiouracil in urine samples
Urine Spiked (120583M) Detecteda (120583M) Bias () Recovery () SD plusmn RSD ()Sample 1 2 2062 31 1031 00301 plusmn 039
Sample 2 4 4040 10 1010 00222 plusmn 055
Sample 3 6 5909 minus15 9848 00099 plusmn 017
Sample 4 8 7813 minus23 9766 00207 plusmn 027
aMean average of five determinations
100 times with the phosphate buffer solution before analysiswithout further pretreatment A quantitative determinationcan be carried out by adding the standard solution of 2-thiouracil into the detection system of urine sample Thecalibration graph was used for the determination of spiked2-thiouracil in urine samples The detection results of foururine samples obtained are listed in Table 5 The recoverydetermined was in the range from 976 to 1031 and theRSD was 034 Thus satisfactory recoveries of the analytefrom the real samples and a good agreement between theconcentration ranges studied and the real ranges encounteredin the urine samples when treated with the drug make thedeveloped method applicable in clinical analysis The typicalsquare wave voltammograms for the 2-thiouracil solution atGCE are shown in Figure 7(b)
4 Conclusion
The main aim of drug analysis is to contribute to theimprovement of drug safety Due to the poor selectivity ofthe titrimetric and spectrophotometric assay methods andthe insufficient precision of the selective HPLC methodnone of these methods can be considered to fulfill thisrequirement Nowadays due to advancement in the field ofelectrochemistry some other types of electrodes are used toget high sensitivity and selectivity of drugs A glassy carbonelectrode was used for the first time for the oxidation of2-thiouracil in phosphate buffer solution A suitable mech-anism was proposed This proposed method can be used
for voltammetric determination of selected analyte as low as016 120583M with good reproducibility The method offered theadvantages of accuracy and time saving as well as simplicityof reagents and apparatus In addition the results obtainedare successfully applied in pharmaceutical formulations andspiked urine samples The proposed method is suitablefor quality control laboratories as well as pharmacokineticstudies with satisfactory result
References
[1] J P Hart Electroanalysis of Biologically Important CompoundsEllis Horwood Chichester UK 1990
[2] J P Hart and I C Hartley ldquoVoltammetric and amperomet-ric studies of thiocholine at a screen-printed carbon elec-trode chemically modified with cobalt phthalocyanine studiestowards a pesticide sensorrdquoThe Analyst vol 119 no 2 pp 259ndash263 1994
[3] A Palumbo M DrsquoIschia and F A Cioffi ldquo2-Thiouracil is aselective inhibitor of neuronal nitric oxide synthase antago-nising tetrahydrobiopterin-dependent enzyme activation anddimerisationrdquo FEBS Letters vol 485 no 2-3 pp 109ndash112 2000
[4] I Roman and R Giurgea ldquoThyroxin and thiouracyl influenceupon some biochemical parameters in chicken thymusesrdquoRomanian Journal of Physiology vol 36 no 1-2 pp 97ndash101 1999
[5] B M Dobyns G E Sheline and J B Workman ldquoMalignantand benign neoplasms of the thyroid in patients treated forhyperthyroidism a report of the cooperative thyrotoxicosistherapy Follow up studyrdquo Journal of Clinical Endocrinology andMetabolism vol 38 no 6 pp 976ndash998 1974
8 International Journal of Electrochemistry
[6] C Anton and C Cristian ldquoDetermination of 2-thiouracyl incomplex samples By liquid chromatography with electrochemi-cal detectionrdquoRomanianBiotechnological Letters vol 7 pp 847ndash854 2002
[7] R N Goyal U P Singh and A A Abdullah ldquoElectrochemicaloxidation of 2-thiouracil at pyrolytic graphite electroderdquo Bio-electrochemistry vol 67 no 1 pp 7ndash13 2005
[8] M Hepel and R A Osteryoung ldquoElectrochemical behavior of2-thiouracil on silver electrodesrdquo Journal of ElectroanalyticalChemistry vol 160 no 1-2 pp 217ndash231 1984
[9] P Swamy and N Vaz ldquoRuthenium(III)- and osmium(VIII)-catalyzed oxidation of 2-thiouracil by bromamine-B in acidand alkaline media a kinetic andmechanistic studyrdquo TransitionMetal Chemistry vol 28 no 4 pp 409ndash417 2003
[10] S Shahrokhian andAHamzehloei ldquoElectrochemical oxidationof catechol in the presence of 2-thiouracil application toelectro-organic synthesisrdquo Electrochemistry Communicationsvol 5 no 8 pp 706ndash710 2003
[11] B Uslu and S A Ozkan ldquoElectrochemical characterisationof nefazodone hydrochloride and voltammetric determinationof the drug in pharmaceuticals and human serumrdquo AnalyticaChimica Acta vol 462 no 1 pp 49ndash57 2002
[12] J-M Kauffmann M P Prete J-C Vire and G J PatriarcheldquoVoltammetry of pharmaceuticals using different types of mod-ified electrodesrdquo Fresenius Zeitschrift fur Analytische Chemievol 321 no 2 pp 172ndash176 1985
[13] F Belal H Abdine and N Zoman ldquoVoltammetric determina-tion of nilvadipine in dosage forms and spiked human urinerdquoJournal of Pharmaceutical and Biomedical Analysis vol 26 no4 pp 585ndash592 2001
[14] P Zuman ldquoCurrent status of polarography and voltammetry inanalytical chemistryrdquo Analytical Letters vol 33 no 2 pp 163ndash174 2000
[15] T B Demircigil S AOzkanO Coruh and S Yilmaz ldquoElectro-chemical behavior of formoterol fumarate and its determinationin capsules for inhalation and human serum using differential-pulse and square-wave voltammetryrdquoElectroanalysis vol 14 pp122ndash127 2002
[16] G D Christian and W C Purdy ldquoThe residual current inorthophosphate mediumrdquo Journal of Electroanalytical Chem-istry vol 3 no 6 pp 363ndash367 1962
[17] B Rezaei and S Damiri ldquoVoltammetric behavior of multi-walled carbon nanotubes modified electrode-hexacyanofer-rate(II) electrocatalyst system as a sensor for determination ofcaptoprilrdquo Sensors and Actuators B vol 134 no 1 pp 324ndash3312008
[18] S ShahrokhianAHamzehloei AThaghani and S RMousavildquoElectrocatalytic oxidation of 2-thiouracil and 2-thiobarbituricacid at a carbon-paste electrode modified with cobalt phthalo-cyaninerdquo Electroanalysis vol 16 no 11 pp 915ndash921 2004
[19] B Eswarappa B S Sherigara and B E Kumaraswamy ldquoElec-trochemical investigation of benzelidene benzyl hydrazide andits derivative schiff bases at glassy carbon electroderdquo Bulletin ofElectrochemistry vol 20 no 1 pp 1ndash6 2004
[20] D K Gosser Cyclic Voltammetry Simulation and Analysis ofReaction Mechansims Vancouver Coastal Health New YorkNY USA 1993
[21] S Corona-Avendano G Alarcon-Angeles M T Ramırez-SilvaG Rosquete-PinaMRomero-Romo andM Palomar-Pardave
ldquoOn the electrochemistry of dopamine in aqueous solution PartI the role of [SDS] on the voltammetric behavior of dopamineon a carbon paste electroderdquo Journal of Electroanalytical Chem-istry vol 609 no 1 pp 17ndash26 2007
Submit your manuscripts athttpwwwhindawicom
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Inorganic ChemistryInternational Journal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
International Journal ofPhotoenergy
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Carbohydrate Chemistry
International Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Advances in
Physical Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom
Analytical Methods in Chemistry
Journal of
Volume 2014
Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
SpectroscopyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Medicinal ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Chromatography Research International
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Applied ChemistryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Theoretical ChemistryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Spectroscopy
Analytical ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Quantum Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Organic Chemistry International
ElectrochemistryInternational Journal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
CatalystsJournal of
International Journal of Electrochemistry 3
minus12 minus08 minus04 0 04 08 12 16 20
50
40
30
20
10
0
minus10
minus20
minus30
minus40
minus50
minus60
minus70
minus80
Potential (V)
AB
C
(a)(b)
Curr
ent1
eminus4
(A)
Figure 1 Cyclic voltammogram obtained for 1mM 2-thiouracil onglassy carbon electrode in pH 42 02M buffer (a) 2-thiouracil and(b) blank run without 2-thiouracil at 120592 = 50mVsminus1 (A and B areoxidation peaks whereas C is reduction peak)
(a)
(g)
minus12 minus08 minus04 0 04 08 12 16 20
50
40
30
20
10
0
minus10
minus20
minus30
minus40
minus50
Potential (V)
Curr
ent1
eminus4
(A)
Figure 2 Influence of pH on the shape of the peaks in phosphatebuffer solution at (a) pH 42 (b) pH 30 (c) pH 50 (d) pH 70 (e)pH 80 (f) pH 92 and (g) pH 104 with potential scan rate 50mVsminus1
Hence phosphate buffers were taken as a supporting elec-trolyte With increasing the pH of the buffer solution thepeak potential shifted to less positive values as shown inFigure 2
The plot of 119864119901
versus pH (Figure 3(a)) shows that thepeak potential is pH dependent The variation of peakcurrent with pH is shown in Figure 3(b) Initially the peakcurrent increased from pH 3 to 42 and then decreased frompH 42 to 104 The voltammetric response was markedlydependent on pH From the experimental results (Figure 2)it is observed that highest peak current and better shape ofthe voltammogram was observed at pH 42 suggesting thatpH is optimal pH value From the plot of current versuspH (Figure 3(b)) it is evident that at pH values higher than10 the half peak potential is rather constant indicating thatin solutions with pH greater than 10 the process is not pHdependent It can be concluded that 2-thiouracil in bufferedsolutions with pH greater than 10 exist mainly as thiolateanions and therefore their equilibrium concentrations do not
0 5 10 15
pH
0
02
04
06
08
1
12
14
16
A
B
Ep
(V)
(a)
pH2 4 6 8 10
0
05
1
15
2
25
3
35
4
45
A
B
1eminus4
(A)
i p
(b)
Figure 3 (a) Influence of pH on the peak potential of 2-thiouracilfor peaks A and B (b) Variation of peak currents of peaks A and Bwith pH
vary by increasing the pH of solution Hence pH variation isrestricted to 104
33 Influence of Scan Rate Useful information involvingelectrochemical mechanism usually can be acquired from therelationship between peak current and scan rate Thereforethe electrochemical behavior of 2-thiouracil at different scanrates from 50 to 250mVsminus1 (Figure 4) was also studiedFrom this we observed that by increasing the scan ratethe peak potential of B was shifted to more positive valuesSimultaneously the width at half-height of peak B increasedIt is suggested that this corresponds to the oxidation of 2-thiouracil dimers formed at the GCE surface The formationof such kind of dimers is well documented in the literature [7](Scheme 2) but they can only be observed when high scanrates are used probably because they have short life time Atthe same time the cathodic peak C is displaced tomore nega-tive values whereas its current increases with the scan rate
4 International Journal of Electrochemistry
minus12 minus08 minus04 0 04 08 12 16 20
50
40
30
20
10
0
minus10
minus20
minus30
minus40
minus50
minus60
Potential (V)
(a)
(b)
(c)(d)
(e)
Curr
ent1
eminus4
(A)
Figure 4 Cyclic voltammograms of 10mM 2-thiouracil on GCEwith different scan rates at (a) 50 (b) 100 (c) 150 (d) 200 and (e)250mVsminus1
There is a good linear relationship between peak currentand scan rate The equations are
119894
119901
(10
minus4 A) = 1606120592 (Vsminus1) + 0253 119903 = 0998
119894
119901
(10
minus4 A) = 2014120592 (Vsminus1) + 0064 119903 = 0997(2)
for peaks A and B respectively as shown in Figure 5(a) Inaddition there was a linear relation between log 119894
119901
and log 120592corresponding to the following equation
log 119894119901
(10
minus4 A) = 0988 log 120592 (Vsminus1) + 1304 119903 = 0998
log 119894119901
(10
minus4 A) = 0892 log 120592 (Vsminus1) + 1165 119903 = 0999(3)
for peaks A and B respectively (Figure 5(b)) The slope of0988 and 0892 is close to the theoretically expected valueof 1 for an adsorption controlled process [20]
The peak potential shifted to more positive values withincreasing the scan rates The linear relationship betweenpeak potential and logarithm of scan rate can be expressedas
119864
119901
(V) = 0126 log 120592 + 0487 119903 = 0901
119864
119901
(V) = 0261 log 120592 + 1598 119903 = 0986(4)
for the peaks A and B respectively (Figure 5(c))Figure 4 depicts a family of CV recorded in the system
at different potential scan rates From this figure it waspossible to gather information shown in Table 1 regardingthe influence of the potential scan rate on the voltammetricparameters of the system From the variation of Δ119864 valueswith the potential scan rate shown in Table 1 one mayconclude in this case that the 2-thiouracil electrochemicaloxidation atGCE is a quasireversiblemass transfer-controlledprocess see Figures 5(a) and 5(d) However the behavior ofthe ratio |119894pc119894pa| for both the peaks (A and B) may indicate
the presence of a coupled chemical reaction [21] On the basisof similar voltammetric behaviour observed in the presentstudy the same mechanism may be proposed as given in [7](Scheme 2)
34 Calibration Curve In order to develop a rapid and sensi-tive voltammetric method for determining the 2-thiouracilwe adopted the square wave voltammetric (SWV) modebecause the peaks were sharper and better defined at lowerconcentration of 2-thiouracil than those obtained by cyclicvoltammetry with low background current resulting inimproved resolution According to the obtained results it waspossible to apply this technique to the quantitative analysisof 2-thiouracil The phosphate buffer solution of pH 42 wasselected as the supporting electrolyte for the quantificationof 2-thiouracil as it gave maximum peak current at pH42 The peak at about 105V in SWV was considered forthe analysis Square wave voltammograms obtained withincreasing amount of 2-thiouracil showed that the peakcurrent increased linearly with increasing concentration asshown in Figures 6(a) and 6(b)
Using the optimum conditions described above linearcalibration curves were obtained for 2-thiouracil in the rangeof 1 to 200120583MThe linear equation was
119894
119901
(120583A) = 0166119862 (120583M) + 7925 (119903 = 0995) (5)
Deviation from linearity was observed for more concen-trated solutions due to the adsorption of oxidation producton the electrode surface It was also observed that thepeak potential (119864
119901
) and half peak potential (119864119901
2) wereshifted towards more positive value suggesting that productundergoes adsorption at the surface of GCE Related statis-tical data of the calibration curve was obtained from fivedifferent calibration curvesThe limit of detection (LOD) andquantification (LOQ)were 016120583Mand053 120583M respectivelyThe LOD and LOQ were calculated using the followingequations
LOD = 3119904119898
LOQ = 10119904119898
(6)
where 119904 is the standard deviation of the peak currents of theblank (five runs) and 119898 is the slope of the calibration curveComparison of earlier methods with the present methodshowed the present method was better for the determinationof 2-thiouracil (Table 2)
35 Stability and Reproducibility In order to study the stabil-ity and reproducibility of the electrode a 10120583M 2-thiouracilsolution was measured with the same electrode (renewedevery time) for every several hours within day the RSDof the peak current was 069 (number of measurements= 5) As to the between-day reproducibility it was similarto that of within a day if the temperature was kept almostunchangedwhich could be attributed to the excellent stabilityand reproducibility of GCE
36 Effect of Interferents For the analytical applications ofthe proposedmethod the effects of potential interferents that
International Journal of Electrochemistry 5
O
NH
SNH
2 2 2
SHN
OH
N
SminusN N N
OH OH OH
N N N
S S
minus2eminus minus2H+
Scheme 2 Proposed mechanism
0 01 02 03
0
1
2
3
4
5
6
A
B
1eminus4
(A)
i p
120592 (Vsminus1)
(a)
log120592 (Vsminus1)0
0
02
04
06
08
1
12
minus15 minus1 minus05
A
B
Logi
p(A
)
(b)
log120592 (Vsminus1)00
02
04
06
08
1
16
14
12
minus15 minus1 minus05
A
B
Ep
(V)
(c)
A
B
02 03 04 05 06
0
1
2
3
4
5
6
120592 12 (Vsminus1)12
i p1eminus4
(A)
(d)
Figure 5 (a) Dependence of the oxidation peak current of peaks A and B on the scan rate (b) Dependence of the logarithm of peak currenton logarithm of scan rate for peaks A and B (c) Relationship between peak potential and logarithm of scan rate for the peaks A and B (d)Relationship between peak current of peaks A and B on the square root of scan rate
Table 1 Variation of the voltammetric parameters as a function of the potential scan rate (120592) corresponding to the CVs shown in Figure 4
120592
(mVsminus1)119864paA(mV)
119864paB(mV)
119864pc(mV)
Δ119864A(119864paA minus 119864pc)
(mV)
Δ119864B(119864paB minus 119864pc)
(mV)
119894paA10minus4 (A)
119894paB10minus4 (A)
119894pc
10minus4 (A)
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
119894pc
119894paA
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
119894pc
119894paB
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
50 326 1256 minus501 827 1757 minus1001 minus1035 1241 1239 1199100 362 1343 minus595 957 1938 minus1920 minus2076 2383 1241 1147150 376 1379 minus614 989 1993 minus2691 minus3201 3125 1161 09762200 385 1403 minus646 103 2049 minus3456 minus4012 3813 1103 09503250 428 1451 minus702 113 2152 minus4251 minus5102 4262 1002 08353
6 International Journal of Electrochemistry
Potential (V)080 085 090 095 100 105 110 115 120
minus02
minus03
minus04
minus05
minus06
minus07
minus08
minus09
minus10
minus11
minus12
(a)
(h)
Curr
ent1
eminus5
(A)
(a)
[2-TU] (120583M)0 10 20 30
minus80
minus85
minus90
minus95
minus100
minus105
minus110
Curr
ent1
eminus6
(A)
(b)
Figure 6 (a) Square wave voltammograms of GCE in 2-thiouracilsolution at different concentrations at (a) 1 (b) 3 (c) 5 (d) 7 (e) 9(f) 10 (g) 15 and (h) 20120583M and (b) plot of the peak current againstconcentration of 2-thiouracil
Table 2 Comparison of some methods for the determination of 2-thiouracil with the proposed method
Analytical method Linearity range(mM)
Detection limit(120583M) Ref
LiquidChromatography (05ndash40) (043) [6]
Carbon-pasteelectrode modifiedwith CoPc
(07ndash800) (40) [18]
Glassy carbonelectrode (0001ndash0015) (016) This work
are likely to be in biological samples were evaluated underthe optimum experimental conditions Square wave voltam-metric experiments were carried out for 10120583M 2-thiouracilin the presence of 10mM of each of the interferents Theexperimental results (Table 3) showed that thousand-fold
Table 3 Influence of potential interferents on the voltammetricresponse of 10 120583M 2-thiouracil
Interferents Concentration (mM) Signal change ()Citric acid 10395 018Dextrose 10320 093D-glucose 10850 minus44Gum acacia 09916 50Oxalic acid 10157 26Starch 10162 25Sucrose 10719 minus31
Table 4 Results of the assay and the recovery test of 2TU inpharmaceutical preparations using square wave voltammetry
Propylthiouracil tabletLabeled claim (mg) 500Amount found (mg)a 490RSD () 065Bias () minus20Added (mg) 500Found (mg)a 492Recovered () 984RSD () 038Calculated 119865 124Calculated 119905 216Bias () minus16aMean average of five determinations
excess of glucose starch sucrose dextrose gum acacia citricacid and oxalic acid did not interfere with the voltammetricsignal of 2-thiouracilTherefore the proposedmethod can beused as a selective method
37 Tablet Analysis and Recovery Test In order toevaluate the applicability of the proposed method thecommercial medicinal sample containing 2-thiouracilfrom Propylthiouracil India was studied The tablets weregrounded to powder dissolved in water and then furtherdiluted so that 2-thiouracil concentration falls in the rangeof calibration plot Square wave voltammograms werethen recorded under exactly identical conditions that wereemployed while recording square wave voltammogramsfor plotting calibration plot It was found that 2-thiouracilconcentration determined for various tablets using thismethod are in good agreement with the reported valuesThe values of experimentally determined 2-thiouraciland its amounts agreed reasonably well (Table 4)The typical square wave voltammograms for the 6-propylthiouracil solution at GCE are shown in Figure 7(a)
38 Detection of 2-Thiouracil in Urine Samples The appli-cability of the SWV to the determination of 2-thiouracilin spiked urine was also investigated The recoveries fromurine were measured by spiking drug-free urine with knownamounts of 2-thiouracil The urine samples were diluted
International Journal of Electrochemistry 7
080 090 100 110 120 130 140
(i)(ii)
(iii)
minus10
minus20
minus30
minus40
minus50
minus60
minus70
minus80
minus90
Potential (V)
Curr
ent1
eminus6
(A)
(a)
080 085 090 095 100 105 110 115 120minus30
minus40
minus50
minus60
minus70
minus80
minus90
minus100
(i)
(ii)
(iii)
Potential (V)
Curr
ent1
eminus6
(A)
(b)
Figure 7 Typical square wave voltammograms on GCE in (a) 6-propylthiouracil solution at different concentrations (i) 2 120583M (ii) 4 120583M and(iii) 6120583M in tablet solutions and (b) 2-thiouracil solution at different concentrations (i) 2 120583M (ii) 4120583M and (iii) 6120583M in urine samples
Table 5 Determination of 2-thiouracil in urine samples
Urine Spiked (120583M) Detecteda (120583M) Bias () Recovery () SD plusmn RSD ()Sample 1 2 2062 31 1031 00301 plusmn 039
Sample 2 4 4040 10 1010 00222 plusmn 055
Sample 3 6 5909 minus15 9848 00099 plusmn 017
Sample 4 8 7813 minus23 9766 00207 plusmn 027
aMean average of five determinations
100 times with the phosphate buffer solution before analysiswithout further pretreatment A quantitative determinationcan be carried out by adding the standard solution of 2-thiouracil into the detection system of urine sample Thecalibration graph was used for the determination of spiked2-thiouracil in urine samples The detection results of foururine samples obtained are listed in Table 5 The recoverydetermined was in the range from 976 to 1031 and theRSD was 034 Thus satisfactory recoveries of the analytefrom the real samples and a good agreement between theconcentration ranges studied and the real ranges encounteredin the urine samples when treated with the drug make thedeveloped method applicable in clinical analysis The typicalsquare wave voltammograms for the 2-thiouracil solution atGCE are shown in Figure 7(b)
4 Conclusion
The main aim of drug analysis is to contribute to theimprovement of drug safety Due to the poor selectivity ofthe titrimetric and spectrophotometric assay methods andthe insufficient precision of the selective HPLC methodnone of these methods can be considered to fulfill thisrequirement Nowadays due to advancement in the field ofelectrochemistry some other types of electrodes are used toget high sensitivity and selectivity of drugs A glassy carbonelectrode was used for the first time for the oxidation of2-thiouracil in phosphate buffer solution A suitable mech-anism was proposed This proposed method can be used
for voltammetric determination of selected analyte as low as016 120583M with good reproducibility The method offered theadvantages of accuracy and time saving as well as simplicityof reagents and apparatus In addition the results obtainedare successfully applied in pharmaceutical formulations andspiked urine samples The proposed method is suitablefor quality control laboratories as well as pharmacokineticstudies with satisfactory result
References
[1] J P Hart Electroanalysis of Biologically Important CompoundsEllis Horwood Chichester UK 1990
[2] J P Hart and I C Hartley ldquoVoltammetric and amperomet-ric studies of thiocholine at a screen-printed carbon elec-trode chemically modified with cobalt phthalocyanine studiestowards a pesticide sensorrdquoThe Analyst vol 119 no 2 pp 259ndash263 1994
[3] A Palumbo M DrsquoIschia and F A Cioffi ldquo2-Thiouracil is aselective inhibitor of neuronal nitric oxide synthase antago-nising tetrahydrobiopterin-dependent enzyme activation anddimerisationrdquo FEBS Letters vol 485 no 2-3 pp 109ndash112 2000
[4] I Roman and R Giurgea ldquoThyroxin and thiouracyl influenceupon some biochemical parameters in chicken thymusesrdquoRomanian Journal of Physiology vol 36 no 1-2 pp 97ndash101 1999
[5] B M Dobyns G E Sheline and J B Workman ldquoMalignantand benign neoplasms of the thyroid in patients treated forhyperthyroidism a report of the cooperative thyrotoxicosistherapy Follow up studyrdquo Journal of Clinical Endocrinology andMetabolism vol 38 no 6 pp 976ndash998 1974
8 International Journal of Electrochemistry
[6] C Anton and C Cristian ldquoDetermination of 2-thiouracyl incomplex samples By liquid chromatography with electrochemi-cal detectionrdquoRomanianBiotechnological Letters vol 7 pp 847ndash854 2002
[7] R N Goyal U P Singh and A A Abdullah ldquoElectrochemicaloxidation of 2-thiouracil at pyrolytic graphite electroderdquo Bio-electrochemistry vol 67 no 1 pp 7ndash13 2005
[8] M Hepel and R A Osteryoung ldquoElectrochemical behavior of2-thiouracil on silver electrodesrdquo Journal of ElectroanalyticalChemistry vol 160 no 1-2 pp 217ndash231 1984
[9] P Swamy and N Vaz ldquoRuthenium(III)- and osmium(VIII)-catalyzed oxidation of 2-thiouracil by bromamine-B in acidand alkaline media a kinetic andmechanistic studyrdquo TransitionMetal Chemistry vol 28 no 4 pp 409ndash417 2003
[10] S Shahrokhian andAHamzehloei ldquoElectrochemical oxidationof catechol in the presence of 2-thiouracil application toelectro-organic synthesisrdquo Electrochemistry Communicationsvol 5 no 8 pp 706ndash710 2003
[11] B Uslu and S A Ozkan ldquoElectrochemical characterisationof nefazodone hydrochloride and voltammetric determinationof the drug in pharmaceuticals and human serumrdquo AnalyticaChimica Acta vol 462 no 1 pp 49ndash57 2002
[12] J-M Kauffmann M P Prete J-C Vire and G J PatriarcheldquoVoltammetry of pharmaceuticals using different types of mod-ified electrodesrdquo Fresenius Zeitschrift fur Analytische Chemievol 321 no 2 pp 172ndash176 1985
[13] F Belal H Abdine and N Zoman ldquoVoltammetric determina-tion of nilvadipine in dosage forms and spiked human urinerdquoJournal of Pharmaceutical and Biomedical Analysis vol 26 no4 pp 585ndash592 2001
[14] P Zuman ldquoCurrent status of polarography and voltammetry inanalytical chemistryrdquo Analytical Letters vol 33 no 2 pp 163ndash174 2000
[15] T B Demircigil S AOzkanO Coruh and S Yilmaz ldquoElectro-chemical behavior of formoterol fumarate and its determinationin capsules for inhalation and human serum using differential-pulse and square-wave voltammetryrdquoElectroanalysis vol 14 pp122ndash127 2002
[16] G D Christian and W C Purdy ldquoThe residual current inorthophosphate mediumrdquo Journal of Electroanalytical Chem-istry vol 3 no 6 pp 363ndash367 1962
[17] B Rezaei and S Damiri ldquoVoltammetric behavior of multi-walled carbon nanotubes modified electrode-hexacyanofer-rate(II) electrocatalyst system as a sensor for determination ofcaptoprilrdquo Sensors and Actuators B vol 134 no 1 pp 324ndash3312008
[18] S ShahrokhianAHamzehloei AThaghani and S RMousavildquoElectrocatalytic oxidation of 2-thiouracil and 2-thiobarbituricacid at a carbon-paste electrode modified with cobalt phthalo-cyaninerdquo Electroanalysis vol 16 no 11 pp 915ndash921 2004
[19] B Eswarappa B S Sherigara and B E Kumaraswamy ldquoElec-trochemical investigation of benzelidene benzyl hydrazide andits derivative schiff bases at glassy carbon electroderdquo Bulletin ofElectrochemistry vol 20 no 1 pp 1ndash6 2004
[20] D K Gosser Cyclic Voltammetry Simulation and Analysis ofReaction Mechansims Vancouver Coastal Health New YorkNY USA 1993
[21] S Corona-Avendano G Alarcon-Angeles M T Ramırez-SilvaG Rosquete-PinaMRomero-Romo andM Palomar-Pardave
ldquoOn the electrochemistry of dopamine in aqueous solution PartI the role of [SDS] on the voltammetric behavior of dopamineon a carbon paste electroderdquo Journal of Electroanalytical Chem-istry vol 609 no 1 pp 17ndash26 2007
Submit your manuscripts athttpwwwhindawicom
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Inorganic ChemistryInternational Journal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
International Journal ofPhotoenergy
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Carbohydrate Chemistry
International Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Advances in
Physical Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom
Analytical Methods in Chemistry
Journal of
Volume 2014
Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
SpectroscopyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Medicinal ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Chromatography Research International
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Applied ChemistryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Theoretical ChemistryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Spectroscopy
Analytical ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Quantum Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Organic Chemistry International
ElectrochemistryInternational Journal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
CatalystsJournal of
4 International Journal of Electrochemistry
minus12 minus08 minus04 0 04 08 12 16 20
50
40
30
20
10
0
minus10
minus20
minus30
minus40
minus50
minus60
Potential (V)
(a)
(b)
(c)(d)
(e)
Curr
ent1
eminus4
(A)
Figure 4 Cyclic voltammograms of 10mM 2-thiouracil on GCEwith different scan rates at (a) 50 (b) 100 (c) 150 (d) 200 and (e)250mVsminus1
There is a good linear relationship between peak currentand scan rate The equations are
119894
119901
(10
minus4 A) = 1606120592 (Vsminus1) + 0253 119903 = 0998
119894
119901
(10
minus4 A) = 2014120592 (Vsminus1) + 0064 119903 = 0997(2)
for peaks A and B respectively as shown in Figure 5(a) Inaddition there was a linear relation between log 119894
119901
and log 120592corresponding to the following equation
log 119894119901
(10
minus4 A) = 0988 log 120592 (Vsminus1) + 1304 119903 = 0998
log 119894119901
(10
minus4 A) = 0892 log 120592 (Vsminus1) + 1165 119903 = 0999(3)
for peaks A and B respectively (Figure 5(b)) The slope of0988 and 0892 is close to the theoretically expected valueof 1 for an adsorption controlled process [20]
The peak potential shifted to more positive values withincreasing the scan rates The linear relationship betweenpeak potential and logarithm of scan rate can be expressedas
119864
119901
(V) = 0126 log 120592 + 0487 119903 = 0901
119864
119901
(V) = 0261 log 120592 + 1598 119903 = 0986(4)
for the peaks A and B respectively (Figure 5(c))Figure 4 depicts a family of CV recorded in the system
at different potential scan rates From this figure it waspossible to gather information shown in Table 1 regardingthe influence of the potential scan rate on the voltammetricparameters of the system From the variation of Δ119864 valueswith the potential scan rate shown in Table 1 one mayconclude in this case that the 2-thiouracil electrochemicaloxidation atGCE is a quasireversiblemass transfer-controlledprocess see Figures 5(a) and 5(d) However the behavior ofthe ratio |119894pc119894pa| for both the peaks (A and B) may indicate
the presence of a coupled chemical reaction [21] On the basisof similar voltammetric behaviour observed in the presentstudy the same mechanism may be proposed as given in [7](Scheme 2)
34 Calibration Curve In order to develop a rapid and sensi-tive voltammetric method for determining the 2-thiouracilwe adopted the square wave voltammetric (SWV) modebecause the peaks were sharper and better defined at lowerconcentration of 2-thiouracil than those obtained by cyclicvoltammetry with low background current resulting inimproved resolution According to the obtained results it waspossible to apply this technique to the quantitative analysisof 2-thiouracil The phosphate buffer solution of pH 42 wasselected as the supporting electrolyte for the quantificationof 2-thiouracil as it gave maximum peak current at pH42 The peak at about 105V in SWV was considered forthe analysis Square wave voltammograms obtained withincreasing amount of 2-thiouracil showed that the peakcurrent increased linearly with increasing concentration asshown in Figures 6(a) and 6(b)
Using the optimum conditions described above linearcalibration curves were obtained for 2-thiouracil in the rangeof 1 to 200120583MThe linear equation was
119894
119901
(120583A) = 0166119862 (120583M) + 7925 (119903 = 0995) (5)
Deviation from linearity was observed for more concen-trated solutions due to the adsorption of oxidation producton the electrode surface It was also observed that thepeak potential (119864
119901
) and half peak potential (119864119901
2) wereshifted towards more positive value suggesting that productundergoes adsorption at the surface of GCE Related statis-tical data of the calibration curve was obtained from fivedifferent calibration curvesThe limit of detection (LOD) andquantification (LOQ)were 016120583Mand053 120583M respectivelyThe LOD and LOQ were calculated using the followingequations
LOD = 3119904119898
LOQ = 10119904119898
(6)
where 119904 is the standard deviation of the peak currents of theblank (five runs) and 119898 is the slope of the calibration curveComparison of earlier methods with the present methodshowed the present method was better for the determinationof 2-thiouracil (Table 2)
35 Stability and Reproducibility In order to study the stabil-ity and reproducibility of the electrode a 10120583M 2-thiouracilsolution was measured with the same electrode (renewedevery time) for every several hours within day the RSDof the peak current was 069 (number of measurements= 5) As to the between-day reproducibility it was similarto that of within a day if the temperature was kept almostunchangedwhich could be attributed to the excellent stabilityand reproducibility of GCE
36 Effect of Interferents For the analytical applications ofthe proposedmethod the effects of potential interferents that
International Journal of Electrochemistry 5
O
NH
SNH
2 2 2
SHN
OH
N
SminusN N N
OH OH OH
N N N
S S
minus2eminus minus2H+
Scheme 2 Proposed mechanism
0 01 02 03
0
1
2
3
4
5
6
A
B
1eminus4
(A)
i p
120592 (Vsminus1)
(a)
log120592 (Vsminus1)0
0
02
04
06
08
1
12
minus15 minus1 minus05
A
B
Logi
p(A
)
(b)
log120592 (Vsminus1)00
02
04
06
08
1
16
14
12
minus15 minus1 minus05
A
B
Ep
(V)
(c)
A
B
02 03 04 05 06
0
1
2
3
4
5
6
120592 12 (Vsminus1)12
i p1eminus4
(A)
(d)
Figure 5 (a) Dependence of the oxidation peak current of peaks A and B on the scan rate (b) Dependence of the logarithm of peak currenton logarithm of scan rate for peaks A and B (c) Relationship between peak potential and logarithm of scan rate for the peaks A and B (d)Relationship between peak current of peaks A and B on the square root of scan rate
Table 1 Variation of the voltammetric parameters as a function of the potential scan rate (120592) corresponding to the CVs shown in Figure 4
120592
(mVsminus1)119864paA(mV)
119864paB(mV)
119864pc(mV)
Δ119864A(119864paA minus 119864pc)
(mV)
Δ119864B(119864paB minus 119864pc)
(mV)
119894paA10minus4 (A)
119894paB10minus4 (A)
119894pc
10minus4 (A)
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
119894pc
119894paA
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
119894pc
119894paB
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
50 326 1256 minus501 827 1757 minus1001 minus1035 1241 1239 1199100 362 1343 minus595 957 1938 minus1920 minus2076 2383 1241 1147150 376 1379 minus614 989 1993 minus2691 minus3201 3125 1161 09762200 385 1403 minus646 103 2049 minus3456 minus4012 3813 1103 09503250 428 1451 minus702 113 2152 minus4251 minus5102 4262 1002 08353
6 International Journal of Electrochemistry
Potential (V)080 085 090 095 100 105 110 115 120
minus02
minus03
minus04
minus05
minus06
minus07
minus08
minus09
minus10
minus11
minus12
(a)
(h)
Curr
ent1
eminus5
(A)
(a)
[2-TU] (120583M)0 10 20 30
minus80
minus85
minus90
minus95
minus100
minus105
minus110
Curr
ent1
eminus6
(A)
(b)
Figure 6 (a) Square wave voltammograms of GCE in 2-thiouracilsolution at different concentrations at (a) 1 (b) 3 (c) 5 (d) 7 (e) 9(f) 10 (g) 15 and (h) 20120583M and (b) plot of the peak current againstconcentration of 2-thiouracil
Table 2 Comparison of some methods for the determination of 2-thiouracil with the proposed method
Analytical method Linearity range(mM)
Detection limit(120583M) Ref
LiquidChromatography (05ndash40) (043) [6]
Carbon-pasteelectrode modifiedwith CoPc
(07ndash800) (40) [18]
Glassy carbonelectrode (0001ndash0015) (016) This work
are likely to be in biological samples were evaluated underthe optimum experimental conditions Square wave voltam-metric experiments were carried out for 10120583M 2-thiouracilin the presence of 10mM of each of the interferents Theexperimental results (Table 3) showed that thousand-fold
Table 3 Influence of potential interferents on the voltammetricresponse of 10 120583M 2-thiouracil
Interferents Concentration (mM) Signal change ()Citric acid 10395 018Dextrose 10320 093D-glucose 10850 minus44Gum acacia 09916 50Oxalic acid 10157 26Starch 10162 25Sucrose 10719 minus31
Table 4 Results of the assay and the recovery test of 2TU inpharmaceutical preparations using square wave voltammetry
Propylthiouracil tabletLabeled claim (mg) 500Amount found (mg)a 490RSD () 065Bias () minus20Added (mg) 500Found (mg)a 492Recovered () 984RSD () 038Calculated 119865 124Calculated 119905 216Bias () minus16aMean average of five determinations
excess of glucose starch sucrose dextrose gum acacia citricacid and oxalic acid did not interfere with the voltammetricsignal of 2-thiouracilTherefore the proposedmethod can beused as a selective method
37 Tablet Analysis and Recovery Test In order toevaluate the applicability of the proposed method thecommercial medicinal sample containing 2-thiouracilfrom Propylthiouracil India was studied The tablets weregrounded to powder dissolved in water and then furtherdiluted so that 2-thiouracil concentration falls in the rangeof calibration plot Square wave voltammograms werethen recorded under exactly identical conditions that wereemployed while recording square wave voltammogramsfor plotting calibration plot It was found that 2-thiouracilconcentration determined for various tablets using thismethod are in good agreement with the reported valuesThe values of experimentally determined 2-thiouraciland its amounts agreed reasonably well (Table 4)The typical square wave voltammograms for the 6-propylthiouracil solution at GCE are shown in Figure 7(a)
38 Detection of 2-Thiouracil in Urine Samples The appli-cability of the SWV to the determination of 2-thiouracilin spiked urine was also investigated The recoveries fromurine were measured by spiking drug-free urine with knownamounts of 2-thiouracil The urine samples were diluted
International Journal of Electrochemistry 7
080 090 100 110 120 130 140
(i)(ii)
(iii)
minus10
minus20
minus30
minus40
minus50
minus60
minus70
minus80
minus90
Potential (V)
Curr
ent1
eminus6
(A)
(a)
080 085 090 095 100 105 110 115 120minus30
minus40
minus50
minus60
minus70
minus80
minus90
minus100
(i)
(ii)
(iii)
Potential (V)
Curr
ent1
eminus6
(A)
(b)
Figure 7 Typical square wave voltammograms on GCE in (a) 6-propylthiouracil solution at different concentrations (i) 2 120583M (ii) 4 120583M and(iii) 6120583M in tablet solutions and (b) 2-thiouracil solution at different concentrations (i) 2 120583M (ii) 4120583M and (iii) 6120583M in urine samples
Table 5 Determination of 2-thiouracil in urine samples
Urine Spiked (120583M) Detecteda (120583M) Bias () Recovery () SD plusmn RSD ()Sample 1 2 2062 31 1031 00301 plusmn 039
Sample 2 4 4040 10 1010 00222 plusmn 055
Sample 3 6 5909 minus15 9848 00099 plusmn 017
Sample 4 8 7813 minus23 9766 00207 plusmn 027
aMean average of five determinations
100 times with the phosphate buffer solution before analysiswithout further pretreatment A quantitative determinationcan be carried out by adding the standard solution of 2-thiouracil into the detection system of urine sample Thecalibration graph was used for the determination of spiked2-thiouracil in urine samples The detection results of foururine samples obtained are listed in Table 5 The recoverydetermined was in the range from 976 to 1031 and theRSD was 034 Thus satisfactory recoveries of the analytefrom the real samples and a good agreement between theconcentration ranges studied and the real ranges encounteredin the urine samples when treated with the drug make thedeveloped method applicable in clinical analysis The typicalsquare wave voltammograms for the 2-thiouracil solution atGCE are shown in Figure 7(b)
4 Conclusion
The main aim of drug analysis is to contribute to theimprovement of drug safety Due to the poor selectivity ofthe titrimetric and spectrophotometric assay methods andthe insufficient precision of the selective HPLC methodnone of these methods can be considered to fulfill thisrequirement Nowadays due to advancement in the field ofelectrochemistry some other types of electrodes are used toget high sensitivity and selectivity of drugs A glassy carbonelectrode was used for the first time for the oxidation of2-thiouracil in phosphate buffer solution A suitable mech-anism was proposed This proposed method can be used
for voltammetric determination of selected analyte as low as016 120583M with good reproducibility The method offered theadvantages of accuracy and time saving as well as simplicityof reagents and apparatus In addition the results obtainedare successfully applied in pharmaceutical formulations andspiked urine samples The proposed method is suitablefor quality control laboratories as well as pharmacokineticstudies with satisfactory result
References
[1] J P Hart Electroanalysis of Biologically Important CompoundsEllis Horwood Chichester UK 1990
[2] J P Hart and I C Hartley ldquoVoltammetric and amperomet-ric studies of thiocholine at a screen-printed carbon elec-trode chemically modified with cobalt phthalocyanine studiestowards a pesticide sensorrdquoThe Analyst vol 119 no 2 pp 259ndash263 1994
[3] A Palumbo M DrsquoIschia and F A Cioffi ldquo2-Thiouracil is aselective inhibitor of neuronal nitric oxide synthase antago-nising tetrahydrobiopterin-dependent enzyme activation anddimerisationrdquo FEBS Letters vol 485 no 2-3 pp 109ndash112 2000
[4] I Roman and R Giurgea ldquoThyroxin and thiouracyl influenceupon some biochemical parameters in chicken thymusesrdquoRomanian Journal of Physiology vol 36 no 1-2 pp 97ndash101 1999
[5] B M Dobyns G E Sheline and J B Workman ldquoMalignantand benign neoplasms of the thyroid in patients treated forhyperthyroidism a report of the cooperative thyrotoxicosistherapy Follow up studyrdquo Journal of Clinical Endocrinology andMetabolism vol 38 no 6 pp 976ndash998 1974
8 International Journal of Electrochemistry
[6] C Anton and C Cristian ldquoDetermination of 2-thiouracyl incomplex samples By liquid chromatography with electrochemi-cal detectionrdquoRomanianBiotechnological Letters vol 7 pp 847ndash854 2002
[7] R N Goyal U P Singh and A A Abdullah ldquoElectrochemicaloxidation of 2-thiouracil at pyrolytic graphite electroderdquo Bio-electrochemistry vol 67 no 1 pp 7ndash13 2005
[8] M Hepel and R A Osteryoung ldquoElectrochemical behavior of2-thiouracil on silver electrodesrdquo Journal of ElectroanalyticalChemistry vol 160 no 1-2 pp 217ndash231 1984
[9] P Swamy and N Vaz ldquoRuthenium(III)- and osmium(VIII)-catalyzed oxidation of 2-thiouracil by bromamine-B in acidand alkaline media a kinetic andmechanistic studyrdquo TransitionMetal Chemistry vol 28 no 4 pp 409ndash417 2003
[10] S Shahrokhian andAHamzehloei ldquoElectrochemical oxidationof catechol in the presence of 2-thiouracil application toelectro-organic synthesisrdquo Electrochemistry Communicationsvol 5 no 8 pp 706ndash710 2003
[11] B Uslu and S A Ozkan ldquoElectrochemical characterisationof nefazodone hydrochloride and voltammetric determinationof the drug in pharmaceuticals and human serumrdquo AnalyticaChimica Acta vol 462 no 1 pp 49ndash57 2002
[12] J-M Kauffmann M P Prete J-C Vire and G J PatriarcheldquoVoltammetry of pharmaceuticals using different types of mod-ified electrodesrdquo Fresenius Zeitschrift fur Analytische Chemievol 321 no 2 pp 172ndash176 1985
[13] F Belal H Abdine and N Zoman ldquoVoltammetric determina-tion of nilvadipine in dosage forms and spiked human urinerdquoJournal of Pharmaceutical and Biomedical Analysis vol 26 no4 pp 585ndash592 2001
[14] P Zuman ldquoCurrent status of polarography and voltammetry inanalytical chemistryrdquo Analytical Letters vol 33 no 2 pp 163ndash174 2000
[15] T B Demircigil S AOzkanO Coruh and S Yilmaz ldquoElectro-chemical behavior of formoterol fumarate and its determinationin capsules for inhalation and human serum using differential-pulse and square-wave voltammetryrdquoElectroanalysis vol 14 pp122ndash127 2002
[16] G D Christian and W C Purdy ldquoThe residual current inorthophosphate mediumrdquo Journal of Electroanalytical Chem-istry vol 3 no 6 pp 363ndash367 1962
[17] B Rezaei and S Damiri ldquoVoltammetric behavior of multi-walled carbon nanotubes modified electrode-hexacyanofer-rate(II) electrocatalyst system as a sensor for determination ofcaptoprilrdquo Sensors and Actuators B vol 134 no 1 pp 324ndash3312008
[18] S ShahrokhianAHamzehloei AThaghani and S RMousavildquoElectrocatalytic oxidation of 2-thiouracil and 2-thiobarbituricacid at a carbon-paste electrode modified with cobalt phthalo-cyaninerdquo Electroanalysis vol 16 no 11 pp 915ndash921 2004
[19] B Eswarappa B S Sherigara and B E Kumaraswamy ldquoElec-trochemical investigation of benzelidene benzyl hydrazide andits derivative schiff bases at glassy carbon electroderdquo Bulletin ofElectrochemistry vol 20 no 1 pp 1ndash6 2004
[20] D K Gosser Cyclic Voltammetry Simulation and Analysis ofReaction Mechansims Vancouver Coastal Health New YorkNY USA 1993
[21] S Corona-Avendano G Alarcon-Angeles M T Ramırez-SilvaG Rosquete-PinaMRomero-Romo andM Palomar-Pardave
ldquoOn the electrochemistry of dopamine in aqueous solution PartI the role of [SDS] on the voltammetric behavior of dopamineon a carbon paste electroderdquo Journal of Electroanalytical Chem-istry vol 609 no 1 pp 17ndash26 2007
Submit your manuscripts athttpwwwhindawicom
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Inorganic ChemistryInternational Journal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
International Journal ofPhotoenergy
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Carbohydrate Chemistry
International Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Advances in
Physical Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom
Analytical Methods in Chemistry
Journal of
Volume 2014
Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
SpectroscopyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Medicinal ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Chromatography Research International
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Applied ChemistryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Theoretical ChemistryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Spectroscopy
Analytical ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Quantum Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Organic Chemistry International
ElectrochemistryInternational Journal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
CatalystsJournal of
International Journal of Electrochemistry 5
O
NH
SNH
2 2 2
SHN
OH
N
SminusN N N
OH OH OH
N N N
S S
minus2eminus minus2H+
Scheme 2 Proposed mechanism
0 01 02 03
0
1
2
3
4
5
6
A
B
1eminus4
(A)
i p
120592 (Vsminus1)
(a)
log120592 (Vsminus1)0
0
02
04
06
08
1
12
minus15 minus1 minus05
A
B
Logi
p(A
)
(b)
log120592 (Vsminus1)00
02
04
06
08
1
16
14
12
minus15 minus1 minus05
A
B
Ep
(V)
(c)
A
B
02 03 04 05 06
0
1
2
3
4
5
6
120592 12 (Vsminus1)12
i p1eminus4
(A)
(d)
Figure 5 (a) Dependence of the oxidation peak current of peaks A and B on the scan rate (b) Dependence of the logarithm of peak currenton logarithm of scan rate for peaks A and B (c) Relationship between peak potential and logarithm of scan rate for the peaks A and B (d)Relationship between peak current of peaks A and B on the square root of scan rate
Table 1 Variation of the voltammetric parameters as a function of the potential scan rate (120592) corresponding to the CVs shown in Figure 4
120592
(mVsminus1)119864paA(mV)
119864paB(mV)
119864pc(mV)
Δ119864A(119864paA minus 119864pc)
(mV)
Δ119864B(119864paB minus 119864pc)
(mV)
119894paA10minus4 (A)
119894paB10minus4 (A)
119894pc
10minus4 (A)
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
119894pc
119894paA
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
119894pc
119894paB
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
1003816
50 326 1256 minus501 827 1757 minus1001 minus1035 1241 1239 1199100 362 1343 minus595 957 1938 minus1920 minus2076 2383 1241 1147150 376 1379 minus614 989 1993 minus2691 minus3201 3125 1161 09762200 385 1403 minus646 103 2049 minus3456 minus4012 3813 1103 09503250 428 1451 minus702 113 2152 minus4251 minus5102 4262 1002 08353
6 International Journal of Electrochemistry
Potential (V)080 085 090 095 100 105 110 115 120
minus02
minus03
minus04
minus05
minus06
minus07
minus08
minus09
minus10
minus11
minus12
(a)
(h)
Curr
ent1
eminus5
(A)
(a)
[2-TU] (120583M)0 10 20 30
minus80
minus85
minus90
minus95
minus100
minus105
minus110
Curr
ent1
eminus6
(A)
(b)
Figure 6 (a) Square wave voltammograms of GCE in 2-thiouracilsolution at different concentrations at (a) 1 (b) 3 (c) 5 (d) 7 (e) 9(f) 10 (g) 15 and (h) 20120583M and (b) plot of the peak current againstconcentration of 2-thiouracil
Table 2 Comparison of some methods for the determination of 2-thiouracil with the proposed method
Analytical method Linearity range(mM)
Detection limit(120583M) Ref
LiquidChromatography (05ndash40) (043) [6]
Carbon-pasteelectrode modifiedwith CoPc
(07ndash800) (40) [18]
Glassy carbonelectrode (0001ndash0015) (016) This work
are likely to be in biological samples were evaluated underthe optimum experimental conditions Square wave voltam-metric experiments were carried out for 10120583M 2-thiouracilin the presence of 10mM of each of the interferents Theexperimental results (Table 3) showed that thousand-fold
Table 3 Influence of potential interferents on the voltammetricresponse of 10 120583M 2-thiouracil
Interferents Concentration (mM) Signal change ()Citric acid 10395 018Dextrose 10320 093D-glucose 10850 minus44Gum acacia 09916 50Oxalic acid 10157 26Starch 10162 25Sucrose 10719 minus31
Table 4 Results of the assay and the recovery test of 2TU inpharmaceutical preparations using square wave voltammetry
Propylthiouracil tabletLabeled claim (mg) 500Amount found (mg)a 490RSD () 065Bias () minus20Added (mg) 500Found (mg)a 492Recovered () 984RSD () 038Calculated 119865 124Calculated 119905 216Bias () minus16aMean average of five determinations
excess of glucose starch sucrose dextrose gum acacia citricacid and oxalic acid did not interfere with the voltammetricsignal of 2-thiouracilTherefore the proposedmethod can beused as a selective method
37 Tablet Analysis and Recovery Test In order toevaluate the applicability of the proposed method thecommercial medicinal sample containing 2-thiouracilfrom Propylthiouracil India was studied The tablets weregrounded to powder dissolved in water and then furtherdiluted so that 2-thiouracil concentration falls in the rangeof calibration plot Square wave voltammograms werethen recorded under exactly identical conditions that wereemployed while recording square wave voltammogramsfor plotting calibration plot It was found that 2-thiouracilconcentration determined for various tablets using thismethod are in good agreement with the reported valuesThe values of experimentally determined 2-thiouraciland its amounts agreed reasonably well (Table 4)The typical square wave voltammograms for the 6-propylthiouracil solution at GCE are shown in Figure 7(a)
38 Detection of 2-Thiouracil in Urine Samples The appli-cability of the SWV to the determination of 2-thiouracilin spiked urine was also investigated The recoveries fromurine were measured by spiking drug-free urine with knownamounts of 2-thiouracil The urine samples were diluted
International Journal of Electrochemistry 7
080 090 100 110 120 130 140
(i)(ii)
(iii)
minus10
minus20
minus30
minus40
minus50
minus60
minus70
minus80
minus90
Potential (V)
Curr
ent1
eminus6
(A)
(a)
080 085 090 095 100 105 110 115 120minus30
minus40
minus50
minus60
minus70
minus80
minus90
minus100
(i)
(ii)
(iii)
Potential (V)
Curr
ent1
eminus6
(A)
(b)
Figure 7 Typical square wave voltammograms on GCE in (a) 6-propylthiouracil solution at different concentrations (i) 2 120583M (ii) 4 120583M and(iii) 6120583M in tablet solutions and (b) 2-thiouracil solution at different concentrations (i) 2 120583M (ii) 4120583M and (iii) 6120583M in urine samples
Table 5 Determination of 2-thiouracil in urine samples
Urine Spiked (120583M) Detecteda (120583M) Bias () Recovery () SD plusmn RSD ()Sample 1 2 2062 31 1031 00301 plusmn 039
Sample 2 4 4040 10 1010 00222 plusmn 055
Sample 3 6 5909 minus15 9848 00099 plusmn 017
Sample 4 8 7813 minus23 9766 00207 plusmn 027
aMean average of five determinations
100 times with the phosphate buffer solution before analysiswithout further pretreatment A quantitative determinationcan be carried out by adding the standard solution of 2-thiouracil into the detection system of urine sample Thecalibration graph was used for the determination of spiked2-thiouracil in urine samples The detection results of foururine samples obtained are listed in Table 5 The recoverydetermined was in the range from 976 to 1031 and theRSD was 034 Thus satisfactory recoveries of the analytefrom the real samples and a good agreement between theconcentration ranges studied and the real ranges encounteredin the urine samples when treated with the drug make thedeveloped method applicable in clinical analysis The typicalsquare wave voltammograms for the 2-thiouracil solution atGCE are shown in Figure 7(b)
4 Conclusion
The main aim of drug analysis is to contribute to theimprovement of drug safety Due to the poor selectivity ofthe titrimetric and spectrophotometric assay methods andthe insufficient precision of the selective HPLC methodnone of these methods can be considered to fulfill thisrequirement Nowadays due to advancement in the field ofelectrochemistry some other types of electrodes are used toget high sensitivity and selectivity of drugs A glassy carbonelectrode was used for the first time for the oxidation of2-thiouracil in phosphate buffer solution A suitable mech-anism was proposed This proposed method can be used
for voltammetric determination of selected analyte as low as016 120583M with good reproducibility The method offered theadvantages of accuracy and time saving as well as simplicityof reagents and apparatus In addition the results obtainedare successfully applied in pharmaceutical formulations andspiked urine samples The proposed method is suitablefor quality control laboratories as well as pharmacokineticstudies with satisfactory result
References
[1] J P Hart Electroanalysis of Biologically Important CompoundsEllis Horwood Chichester UK 1990
[2] J P Hart and I C Hartley ldquoVoltammetric and amperomet-ric studies of thiocholine at a screen-printed carbon elec-trode chemically modified with cobalt phthalocyanine studiestowards a pesticide sensorrdquoThe Analyst vol 119 no 2 pp 259ndash263 1994
[3] A Palumbo M DrsquoIschia and F A Cioffi ldquo2-Thiouracil is aselective inhibitor of neuronal nitric oxide synthase antago-nising tetrahydrobiopterin-dependent enzyme activation anddimerisationrdquo FEBS Letters vol 485 no 2-3 pp 109ndash112 2000
[4] I Roman and R Giurgea ldquoThyroxin and thiouracyl influenceupon some biochemical parameters in chicken thymusesrdquoRomanian Journal of Physiology vol 36 no 1-2 pp 97ndash101 1999
[5] B M Dobyns G E Sheline and J B Workman ldquoMalignantand benign neoplasms of the thyroid in patients treated forhyperthyroidism a report of the cooperative thyrotoxicosistherapy Follow up studyrdquo Journal of Clinical Endocrinology andMetabolism vol 38 no 6 pp 976ndash998 1974
8 International Journal of Electrochemistry
[6] C Anton and C Cristian ldquoDetermination of 2-thiouracyl incomplex samples By liquid chromatography with electrochemi-cal detectionrdquoRomanianBiotechnological Letters vol 7 pp 847ndash854 2002
[7] R N Goyal U P Singh and A A Abdullah ldquoElectrochemicaloxidation of 2-thiouracil at pyrolytic graphite electroderdquo Bio-electrochemistry vol 67 no 1 pp 7ndash13 2005
[8] M Hepel and R A Osteryoung ldquoElectrochemical behavior of2-thiouracil on silver electrodesrdquo Journal of ElectroanalyticalChemistry vol 160 no 1-2 pp 217ndash231 1984
[9] P Swamy and N Vaz ldquoRuthenium(III)- and osmium(VIII)-catalyzed oxidation of 2-thiouracil by bromamine-B in acidand alkaline media a kinetic andmechanistic studyrdquo TransitionMetal Chemistry vol 28 no 4 pp 409ndash417 2003
[10] S Shahrokhian andAHamzehloei ldquoElectrochemical oxidationof catechol in the presence of 2-thiouracil application toelectro-organic synthesisrdquo Electrochemistry Communicationsvol 5 no 8 pp 706ndash710 2003
[11] B Uslu and S A Ozkan ldquoElectrochemical characterisationof nefazodone hydrochloride and voltammetric determinationof the drug in pharmaceuticals and human serumrdquo AnalyticaChimica Acta vol 462 no 1 pp 49ndash57 2002
[12] J-M Kauffmann M P Prete J-C Vire and G J PatriarcheldquoVoltammetry of pharmaceuticals using different types of mod-ified electrodesrdquo Fresenius Zeitschrift fur Analytische Chemievol 321 no 2 pp 172ndash176 1985
[13] F Belal H Abdine and N Zoman ldquoVoltammetric determina-tion of nilvadipine in dosage forms and spiked human urinerdquoJournal of Pharmaceutical and Biomedical Analysis vol 26 no4 pp 585ndash592 2001
[14] P Zuman ldquoCurrent status of polarography and voltammetry inanalytical chemistryrdquo Analytical Letters vol 33 no 2 pp 163ndash174 2000
[15] T B Demircigil S AOzkanO Coruh and S Yilmaz ldquoElectro-chemical behavior of formoterol fumarate and its determinationin capsules for inhalation and human serum using differential-pulse and square-wave voltammetryrdquoElectroanalysis vol 14 pp122ndash127 2002
[16] G D Christian and W C Purdy ldquoThe residual current inorthophosphate mediumrdquo Journal of Electroanalytical Chem-istry vol 3 no 6 pp 363ndash367 1962
[17] B Rezaei and S Damiri ldquoVoltammetric behavior of multi-walled carbon nanotubes modified electrode-hexacyanofer-rate(II) electrocatalyst system as a sensor for determination ofcaptoprilrdquo Sensors and Actuators B vol 134 no 1 pp 324ndash3312008
[18] S ShahrokhianAHamzehloei AThaghani and S RMousavildquoElectrocatalytic oxidation of 2-thiouracil and 2-thiobarbituricacid at a carbon-paste electrode modified with cobalt phthalo-cyaninerdquo Electroanalysis vol 16 no 11 pp 915ndash921 2004
[19] B Eswarappa B S Sherigara and B E Kumaraswamy ldquoElec-trochemical investigation of benzelidene benzyl hydrazide andits derivative schiff bases at glassy carbon electroderdquo Bulletin ofElectrochemistry vol 20 no 1 pp 1ndash6 2004
[20] D K Gosser Cyclic Voltammetry Simulation and Analysis ofReaction Mechansims Vancouver Coastal Health New YorkNY USA 1993
[21] S Corona-Avendano G Alarcon-Angeles M T Ramırez-SilvaG Rosquete-PinaMRomero-Romo andM Palomar-Pardave
ldquoOn the electrochemistry of dopamine in aqueous solution PartI the role of [SDS] on the voltammetric behavior of dopamineon a carbon paste electroderdquo Journal of Electroanalytical Chem-istry vol 609 no 1 pp 17ndash26 2007
Submit your manuscripts athttpwwwhindawicom
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Inorganic ChemistryInternational Journal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
International Journal ofPhotoenergy
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Carbohydrate Chemistry
International Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Advances in
Physical Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom
Analytical Methods in Chemistry
Journal of
Volume 2014
Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
SpectroscopyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Medicinal ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Chromatography Research International
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Applied ChemistryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Theoretical ChemistryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Spectroscopy
Analytical ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Quantum Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Organic Chemistry International
ElectrochemistryInternational Journal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
CatalystsJournal of
6 International Journal of Electrochemistry
Potential (V)080 085 090 095 100 105 110 115 120
minus02
minus03
minus04
minus05
minus06
minus07
minus08
minus09
minus10
minus11
minus12
(a)
(h)
Curr
ent1
eminus5
(A)
(a)
[2-TU] (120583M)0 10 20 30
minus80
minus85
minus90
minus95
minus100
minus105
minus110
Curr
ent1
eminus6
(A)
(b)
Figure 6 (a) Square wave voltammograms of GCE in 2-thiouracilsolution at different concentrations at (a) 1 (b) 3 (c) 5 (d) 7 (e) 9(f) 10 (g) 15 and (h) 20120583M and (b) plot of the peak current againstconcentration of 2-thiouracil
Table 2 Comparison of some methods for the determination of 2-thiouracil with the proposed method
Analytical method Linearity range(mM)
Detection limit(120583M) Ref
LiquidChromatography (05ndash40) (043) [6]
Carbon-pasteelectrode modifiedwith CoPc
(07ndash800) (40) [18]
Glassy carbonelectrode (0001ndash0015) (016) This work
are likely to be in biological samples were evaluated underthe optimum experimental conditions Square wave voltam-metric experiments were carried out for 10120583M 2-thiouracilin the presence of 10mM of each of the interferents Theexperimental results (Table 3) showed that thousand-fold
Table 3 Influence of potential interferents on the voltammetricresponse of 10 120583M 2-thiouracil
Interferents Concentration (mM) Signal change ()Citric acid 10395 018Dextrose 10320 093D-glucose 10850 minus44Gum acacia 09916 50Oxalic acid 10157 26Starch 10162 25Sucrose 10719 minus31
Table 4 Results of the assay and the recovery test of 2TU inpharmaceutical preparations using square wave voltammetry
Propylthiouracil tabletLabeled claim (mg) 500Amount found (mg)a 490RSD () 065Bias () minus20Added (mg) 500Found (mg)a 492Recovered () 984RSD () 038Calculated 119865 124Calculated 119905 216Bias () minus16aMean average of five determinations
excess of glucose starch sucrose dextrose gum acacia citricacid and oxalic acid did not interfere with the voltammetricsignal of 2-thiouracilTherefore the proposedmethod can beused as a selective method
37 Tablet Analysis and Recovery Test In order toevaluate the applicability of the proposed method thecommercial medicinal sample containing 2-thiouracilfrom Propylthiouracil India was studied The tablets weregrounded to powder dissolved in water and then furtherdiluted so that 2-thiouracil concentration falls in the rangeof calibration plot Square wave voltammograms werethen recorded under exactly identical conditions that wereemployed while recording square wave voltammogramsfor plotting calibration plot It was found that 2-thiouracilconcentration determined for various tablets using thismethod are in good agreement with the reported valuesThe values of experimentally determined 2-thiouraciland its amounts agreed reasonably well (Table 4)The typical square wave voltammograms for the 6-propylthiouracil solution at GCE are shown in Figure 7(a)
38 Detection of 2-Thiouracil in Urine Samples The appli-cability of the SWV to the determination of 2-thiouracilin spiked urine was also investigated The recoveries fromurine were measured by spiking drug-free urine with knownamounts of 2-thiouracil The urine samples were diluted
International Journal of Electrochemistry 7
080 090 100 110 120 130 140
(i)(ii)
(iii)
minus10
minus20
minus30
minus40
minus50
minus60
minus70
minus80
minus90
Potential (V)
Curr
ent1
eminus6
(A)
(a)
080 085 090 095 100 105 110 115 120minus30
minus40
minus50
minus60
minus70
minus80
minus90
minus100
(i)
(ii)
(iii)
Potential (V)
Curr
ent1
eminus6
(A)
(b)
Figure 7 Typical square wave voltammograms on GCE in (a) 6-propylthiouracil solution at different concentrations (i) 2 120583M (ii) 4 120583M and(iii) 6120583M in tablet solutions and (b) 2-thiouracil solution at different concentrations (i) 2 120583M (ii) 4120583M and (iii) 6120583M in urine samples
Table 5 Determination of 2-thiouracil in urine samples
Urine Spiked (120583M) Detecteda (120583M) Bias () Recovery () SD plusmn RSD ()Sample 1 2 2062 31 1031 00301 plusmn 039
Sample 2 4 4040 10 1010 00222 plusmn 055
Sample 3 6 5909 minus15 9848 00099 plusmn 017
Sample 4 8 7813 minus23 9766 00207 plusmn 027
aMean average of five determinations
100 times with the phosphate buffer solution before analysiswithout further pretreatment A quantitative determinationcan be carried out by adding the standard solution of 2-thiouracil into the detection system of urine sample Thecalibration graph was used for the determination of spiked2-thiouracil in urine samples The detection results of foururine samples obtained are listed in Table 5 The recoverydetermined was in the range from 976 to 1031 and theRSD was 034 Thus satisfactory recoveries of the analytefrom the real samples and a good agreement between theconcentration ranges studied and the real ranges encounteredin the urine samples when treated with the drug make thedeveloped method applicable in clinical analysis The typicalsquare wave voltammograms for the 2-thiouracil solution atGCE are shown in Figure 7(b)
4 Conclusion
The main aim of drug analysis is to contribute to theimprovement of drug safety Due to the poor selectivity ofthe titrimetric and spectrophotometric assay methods andthe insufficient precision of the selective HPLC methodnone of these methods can be considered to fulfill thisrequirement Nowadays due to advancement in the field ofelectrochemistry some other types of electrodes are used toget high sensitivity and selectivity of drugs A glassy carbonelectrode was used for the first time for the oxidation of2-thiouracil in phosphate buffer solution A suitable mech-anism was proposed This proposed method can be used
for voltammetric determination of selected analyte as low as016 120583M with good reproducibility The method offered theadvantages of accuracy and time saving as well as simplicityof reagents and apparatus In addition the results obtainedare successfully applied in pharmaceutical formulations andspiked urine samples The proposed method is suitablefor quality control laboratories as well as pharmacokineticstudies with satisfactory result
References
[1] J P Hart Electroanalysis of Biologically Important CompoundsEllis Horwood Chichester UK 1990
[2] J P Hart and I C Hartley ldquoVoltammetric and amperomet-ric studies of thiocholine at a screen-printed carbon elec-trode chemically modified with cobalt phthalocyanine studiestowards a pesticide sensorrdquoThe Analyst vol 119 no 2 pp 259ndash263 1994
[3] A Palumbo M DrsquoIschia and F A Cioffi ldquo2-Thiouracil is aselective inhibitor of neuronal nitric oxide synthase antago-nising tetrahydrobiopterin-dependent enzyme activation anddimerisationrdquo FEBS Letters vol 485 no 2-3 pp 109ndash112 2000
[4] I Roman and R Giurgea ldquoThyroxin and thiouracyl influenceupon some biochemical parameters in chicken thymusesrdquoRomanian Journal of Physiology vol 36 no 1-2 pp 97ndash101 1999
[5] B M Dobyns G E Sheline and J B Workman ldquoMalignantand benign neoplasms of the thyroid in patients treated forhyperthyroidism a report of the cooperative thyrotoxicosistherapy Follow up studyrdquo Journal of Clinical Endocrinology andMetabolism vol 38 no 6 pp 976ndash998 1974
8 International Journal of Electrochemistry
[6] C Anton and C Cristian ldquoDetermination of 2-thiouracyl incomplex samples By liquid chromatography with electrochemi-cal detectionrdquoRomanianBiotechnological Letters vol 7 pp 847ndash854 2002
[7] R N Goyal U P Singh and A A Abdullah ldquoElectrochemicaloxidation of 2-thiouracil at pyrolytic graphite electroderdquo Bio-electrochemistry vol 67 no 1 pp 7ndash13 2005
[8] M Hepel and R A Osteryoung ldquoElectrochemical behavior of2-thiouracil on silver electrodesrdquo Journal of ElectroanalyticalChemistry vol 160 no 1-2 pp 217ndash231 1984
[9] P Swamy and N Vaz ldquoRuthenium(III)- and osmium(VIII)-catalyzed oxidation of 2-thiouracil by bromamine-B in acidand alkaline media a kinetic andmechanistic studyrdquo TransitionMetal Chemistry vol 28 no 4 pp 409ndash417 2003
[10] S Shahrokhian andAHamzehloei ldquoElectrochemical oxidationof catechol in the presence of 2-thiouracil application toelectro-organic synthesisrdquo Electrochemistry Communicationsvol 5 no 8 pp 706ndash710 2003
[11] B Uslu and S A Ozkan ldquoElectrochemical characterisationof nefazodone hydrochloride and voltammetric determinationof the drug in pharmaceuticals and human serumrdquo AnalyticaChimica Acta vol 462 no 1 pp 49ndash57 2002
[12] J-M Kauffmann M P Prete J-C Vire and G J PatriarcheldquoVoltammetry of pharmaceuticals using different types of mod-ified electrodesrdquo Fresenius Zeitschrift fur Analytische Chemievol 321 no 2 pp 172ndash176 1985
[13] F Belal H Abdine and N Zoman ldquoVoltammetric determina-tion of nilvadipine in dosage forms and spiked human urinerdquoJournal of Pharmaceutical and Biomedical Analysis vol 26 no4 pp 585ndash592 2001
[14] P Zuman ldquoCurrent status of polarography and voltammetry inanalytical chemistryrdquo Analytical Letters vol 33 no 2 pp 163ndash174 2000
[15] T B Demircigil S AOzkanO Coruh and S Yilmaz ldquoElectro-chemical behavior of formoterol fumarate and its determinationin capsules for inhalation and human serum using differential-pulse and square-wave voltammetryrdquoElectroanalysis vol 14 pp122ndash127 2002
[16] G D Christian and W C Purdy ldquoThe residual current inorthophosphate mediumrdquo Journal of Electroanalytical Chem-istry vol 3 no 6 pp 363ndash367 1962
[17] B Rezaei and S Damiri ldquoVoltammetric behavior of multi-walled carbon nanotubes modified electrode-hexacyanofer-rate(II) electrocatalyst system as a sensor for determination ofcaptoprilrdquo Sensors and Actuators B vol 134 no 1 pp 324ndash3312008
[18] S ShahrokhianAHamzehloei AThaghani and S RMousavildquoElectrocatalytic oxidation of 2-thiouracil and 2-thiobarbituricacid at a carbon-paste electrode modified with cobalt phthalo-cyaninerdquo Electroanalysis vol 16 no 11 pp 915ndash921 2004
[19] B Eswarappa B S Sherigara and B E Kumaraswamy ldquoElec-trochemical investigation of benzelidene benzyl hydrazide andits derivative schiff bases at glassy carbon electroderdquo Bulletin ofElectrochemistry vol 20 no 1 pp 1ndash6 2004
[20] D K Gosser Cyclic Voltammetry Simulation and Analysis ofReaction Mechansims Vancouver Coastal Health New YorkNY USA 1993
[21] S Corona-Avendano G Alarcon-Angeles M T Ramırez-SilvaG Rosquete-PinaMRomero-Romo andM Palomar-Pardave
ldquoOn the electrochemistry of dopamine in aqueous solution PartI the role of [SDS] on the voltammetric behavior of dopamineon a carbon paste electroderdquo Journal of Electroanalytical Chem-istry vol 609 no 1 pp 17ndash26 2007
Submit your manuscripts athttpwwwhindawicom
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Inorganic ChemistryInternational Journal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
International Journal ofPhotoenergy
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Carbohydrate Chemistry
International Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Advances in
Physical Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom
Analytical Methods in Chemistry
Journal of
Volume 2014
Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
SpectroscopyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Medicinal ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Chromatography Research International
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Applied ChemistryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Theoretical ChemistryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Spectroscopy
Analytical ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Quantum Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Organic Chemistry International
ElectrochemistryInternational Journal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
CatalystsJournal of
International Journal of Electrochemistry 7
080 090 100 110 120 130 140
(i)(ii)
(iii)
minus10
minus20
minus30
minus40
minus50
minus60
minus70
minus80
minus90
Potential (V)
Curr
ent1
eminus6
(A)
(a)
080 085 090 095 100 105 110 115 120minus30
minus40
minus50
minus60
minus70
minus80
minus90
minus100
(i)
(ii)
(iii)
Potential (V)
Curr
ent1
eminus6
(A)
(b)
Figure 7 Typical square wave voltammograms on GCE in (a) 6-propylthiouracil solution at different concentrations (i) 2 120583M (ii) 4 120583M and(iii) 6120583M in tablet solutions and (b) 2-thiouracil solution at different concentrations (i) 2 120583M (ii) 4120583M and (iii) 6120583M in urine samples
Table 5 Determination of 2-thiouracil in urine samples
Urine Spiked (120583M) Detecteda (120583M) Bias () Recovery () SD plusmn RSD ()Sample 1 2 2062 31 1031 00301 plusmn 039
Sample 2 4 4040 10 1010 00222 plusmn 055
Sample 3 6 5909 minus15 9848 00099 plusmn 017
Sample 4 8 7813 minus23 9766 00207 plusmn 027
aMean average of five determinations
100 times with the phosphate buffer solution before analysiswithout further pretreatment A quantitative determinationcan be carried out by adding the standard solution of 2-thiouracil into the detection system of urine sample Thecalibration graph was used for the determination of spiked2-thiouracil in urine samples The detection results of foururine samples obtained are listed in Table 5 The recoverydetermined was in the range from 976 to 1031 and theRSD was 034 Thus satisfactory recoveries of the analytefrom the real samples and a good agreement between theconcentration ranges studied and the real ranges encounteredin the urine samples when treated with the drug make thedeveloped method applicable in clinical analysis The typicalsquare wave voltammograms for the 2-thiouracil solution atGCE are shown in Figure 7(b)
4 Conclusion
The main aim of drug analysis is to contribute to theimprovement of drug safety Due to the poor selectivity ofthe titrimetric and spectrophotometric assay methods andthe insufficient precision of the selective HPLC methodnone of these methods can be considered to fulfill thisrequirement Nowadays due to advancement in the field ofelectrochemistry some other types of electrodes are used toget high sensitivity and selectivity of drugs A glassy carbonelectrode was used for the first time for the oxidation of2-thiouracil in phosphate buffer solution A suitable mech-anism was proposed This proposed method can be used
for voltammetric determination of selected analyte as low as016 120583M with good reproducibility The method offered theadvantages of accuracy and time saving as well as simplicityof reagents and apparatus In addition the results obtainedare successfully applied in pharmaceutical formulations andspiked urine samples The proposed method is suitablefor quality control laboratories as well as pharmacokineticstudies with satisfactory result
References
[1] J P Hart Electroanalysis of Biologically Important CompoundsEllis Horwood Chichester UK 1990
[2] J P Hart and I C Hartley ldquoVoltammetric and amperomet-ric studies of thiocholine at a screen-printed carbon elec-trode chemically modified with cobalt phthalocyanine studiestowards a pesticide sensorrdquoThe Analyst vol 119 no 2 pp 259ndash263 1994
[3] A Palumbo M DrsquoIschia and F A Cioffi ldquo2-Thiouracil is aselective inhibitor of neuronal nitric oxide synthase antago-nising tetrahydrobiopterin-dependent enzyme activation anddimerisationrdquo FEBS Letters vol 485 no 2-3 pp 109ndash112 2000
[4] I Roman and R Giurgea ldquoThyroxin and thiouracyl influenceupon some biochemical parameters in chicken thymusesrdquoRomanian Journal of Physiology vol 36 no 1-2 pp 97ndash101 1999
[5] B M Dobyns G E Sheline and J B Workman ldquoMalignantand benign neoplasms of the thyroid in patients treated forhyperthyroidism a report of the cooperative thyrotoxicosistherapy Follow up studyrdquo Journal of Clinical Endocrinology andMetabolism vol 38 no 6 pp 976ndash998 1974
8 International Journal of Electrochemistry
[6] C Anton and C Cristian ldquoDetermination of 2-thiouracyl incomplex samples By liquid chromatography with electrochemi-cal detectionrdquoRomanianBiotechnological Letters vol 7 pp 847ndash854 2002
[7] R N Goyal U P Singh and A A Abdullah ldquoElectrochemicaloxidation of 2-thiouracil at pyrolytic graphite electroderdquo Bio-electrochemistry vol 67 no 1 pp 7ndash13 2005
[8] M Hepel and R A Osteryoung ldquoElectrochemical behavior of2-thiouracil on silver electrodesrdquo Journal of ElectroanalyticalChemistry vol 160 no 1-2 pp 217ndash231 1984
[9] P Swamy and N Vaz ldquoRuthenium(III)- and osmium(VIII)-catalyzed oxidation of 2-thiouracil by bromamine-B in acidand alkaline media a kinetic andmechanistic studyrdquo TransitionMetal Chemistry vol 28 no 4 pp 409ndash417 2003
[10] S Shahrokhian andAHamzehloei ldquoElectrochemical oxidationof catechol in the presence of 2-thiouracil application toelectro-organic synthesisrdquo Electrochemistry Communicationsvol 5 no 8 pp 706ndash710 2003
[11] B Uslu and S A Ozkan ldquoElectrochemical characterisationof nefazodone hydrochloride and voltammetric determinationof the drug in pharmaceuticals and human serumrdquo AnalyticaChimica Acta vol 462 no 1 pp 49ndash57 2002
[12] J-M Kauffmann M P Prete J-C Vire and G J PatriarcheldquoVoltammetry of pharmaceuticals using different types of mod-ified electrodesrdquo Fresenius Zeitschrift fur Analytische Chemievol 321 no 2 pp 172ndash176 1985
[13] F Belal H Abdine and N Zoman ldquoVoltammetric determina-tion of nilvadipine in dosage forms and spiked human urinerdquoJournal of Pharmaceutical and Biomedical Analysis vol 26 no4 pp 585ndash592 2001
[14] P Zuman ldquoCurrent status of polarography and voltammetry inanalytical chemistryrdquo Analytical Letters vol 33 no 2 pp 163ndash174 2000
[15] T B Demircigil S AOzkanO Coruh and S Yilmaz ldquoElectro-chemical behavior of formoterol fumarate and its determinationin capsules for inhalation and human serum using differential-pulse and square-wave voltammetryrdquoElectroanalysis vol 14 pp122ndash127 2002
[16] G D Christian and W C Purdy ldquoThe residual current inorthophosphate mediumrdquo Journal of Electroanalytical Chem-istry vol 3 no 6 pp 363ndash367 1962
[17] B Rezaei and S Damiri ldquoVoltammetric behavior of multi-walled carbon nanotubes modified electrode-hexacyanofer-rate(II) electrocatalyst system as a sensor for determination ofcaptoprilrdquo Sensors and Actuators B vol 134 no 1 pp 324ndash3312008
[18] S ShahrokhianAHamzehloei AThaghani and S RMousavildquoElectrocatalytic oxidation of 2-thiouracil and 2-thiobarbituricacid at a carbon-paste electrode modified with cobalt phthalo-cyaninerdquo Electroanalysis vol 16 no 11 pp 915ndash921 2004
[19] B Eswarappa B S Sherigara and B E Kumaraswamy ldquoElec-trochemical investigation of benzelidene benzyl hydrazide andits derivative schiff bases at glassy carbon electroderdquo Bulletin ofElectrochemistry vol 20 no 1 pp 1ndash6 2004
[20] D K Gosser Cyclic Voltammetry Simulation and Analysis ofReaction Mechansims Vancouver Coastal Health New YorkNY USA 1993
[21] S Corona-Avendano G Alarcon-Angeles M T Ramırez-SilvaG Rosquete-PinaMRomero-Romo andM Palomar-Pardave
ldquoOn the electrochemistry of dopamine in aqueous solution PartI the role of [SDS] on the voltammetric behavior of dopamineon a carbon paste electroderdquo Journal of Electroanalytical Chem-istry vol 609 no 1 pp 17ndash26 2007
Submit your manuscripts athttpwwwhindawicom
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Inorganic ChemistryInternational Journal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
International Journal ofPhotoenergy
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Carbohydrate Chemistry
International Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Advances in
Physical Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom
Analytical Methods in Chemistry
Journal of
Volume 2014
Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
SpectroscopyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Medicinal ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Chromatography Research International
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Applied ChemistryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Theoretical ChemistryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Spectroscopy
Analytical ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Quantum Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Organic Chemistry International
ElectrochemistryInternational Journal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
CatalystsJournal of
8 International Journal of Electrochemistry
[6] C Anton and C Cristian ldquoDetermination of 2-thiouracyl incomplex samples By liquid chromatography with electrochemi-cal detectionrdquoRomanianBiotechnological Letters vol 7 pp 847ndash854 2002
[7] R N Goyal U P Singh and A A Abdullah ldquoElectrochemicaloxidation of 2-thiouracil at pyrolytic graphite electroderdquo Bio-electrochemistry vol 67 no 1 pp 7ndash13 2005
[8] M Hepel and R A Osteryoung ldquoElectrochemical behavior of2-thiouracil on silver electrodesrdquo Journal of ElectroanalyticalChemistry vol 160 no 1-2 pp 217ndash231 1984
[9] P Swamy and N Vaz ldquoRuthenium(III)- and osmium(VIII)-catalyzed oxidation of 2-thiouracil by bromamine-B in acidand alkaline media a kinetic andmechanistic studyrdquo TransitionMetal Chemistry vol 28 no 4 pp 409ndash417 2003
[10] S Shahrokhian andAHamzehloei ldquoElectrochemical oxidationof catechol in the presence of 2-thiouracil application toelectro-organic synthesisrdquo Electrochemistry Communicationsvol 5 no 8 pp 706ndash710 2003
[11] B Uslu and S A Ozkan ldquoElectrochemical characterisationof nefazodone hydrochloride and voltammetric determinationof the drug in pharmaceuticals and human serumrdquo AnalyticaChimica Acta vol 462 no 1 pp 49ndash57 2002
[12] J-M Kauffmann M P Prete J-C Vire and G J PatriarcheldquoVoltammetry of pharmaceuticals using different types of mod-ified electrodesrdquo Fresenius Zeitschrift fur Analytische Chemievol 321 no 2 pp 172ndash176 1985
[13] F Belal H Abdine and N Zoman ldquoVoltammetric determina-tion of nilvadipine in dosage forms and spiked human urinerdquoJournal of Pharmaceutical and Biomedical Analysis vol 26 no4 pp 585ndash592 2001
[14] P Zuman ldquoCurrent status of polarography and voltammetry inanalytical chemistryrdquo Analytical Letters vol 33 no 2 pp 163ndash174 2000
[15] T B Demircigil S AOzkanO Coruh and S Yilmaz ldquoElectro-chemical behavior of formoterol fumarate and its determinationin capsules for inhalation and human serum using differential-pulse and square-wave voltammetryrdquoElectroanalysis vol 14 pp122ndash127 2002
[16] G D Christian and W C Purdy ldquoThe residual current inorthophosphate mediumrdquo Journal of Electroanalytical Chem-istry vol 3 no 6 pp 363ndash367 1962
[17] B Rezaei and S Damiri ldquoVoltammetric behavior of multi-walled carbon nanotubes modified electrode-hexacyanofer-rate(II) electrocatalyst system as a sensor for determination ofcaptoprilrdquo Sensors and Actuators B vol 134 no 1 pp 324ndash3312008
[18] S ShahrokhianAHamzehloei AThaghani and S RMousavildquoElectrocatalytic oxidation of 2-thiouracil and 2-thiobarbituricacid at a carbon-paste electrode modified with cobalt phthalo-cyaninerdquo Electroanalysis vol 16 no 11 pp 915ndash921 2004
[19] B Eswarappa B S Sherigara and B E Kumaraswamy ldquoElec-trochemical investigation of benzelidene benzyl hydrazide andits derivative schiff bases at glassy carbon electroderdquo Bulletin ofElectrochemistry vol 20 no 1 pp 1ndash6 2004
[20] D K Gosser Cyclic Voltammetry Simulation and Analysis ofReaction Mechansims Vancouver Coastal Health New YorkNY USA 1993
[21] S Corona-Avendano G Alarcon-Angeles M T Ramırez-SilvaG Rosquete-PinaMRomero-Romo andM Palomar-Pardave
ldquoOn the electrochemistry of dopamine in aqueous solution PartI the role of [SDS] on the voltammetric behavior of dopamineon a carbon paste electroderdquo Journal of Electroanalytical Chem-istry vol 609 no 1 pp 17ndash26 2007
Submit your manuscripts athttpwwwhindawicom
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Inorganic ChemistryInternational Journal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
International Journal ofPhotoenergy
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Carbohydrate Chemistry
International Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Advances in
Physical Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom
Analytical Methods in Chemistry
Journal of
Volume 2014
Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
SpectroscopyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Medicinal ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Chromatography Research International
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Applied ChemistryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Theoretical ChemistryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Spectroscopy
Analytical ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Quantum Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Organic Chemistry International
ElectrochemistryInternational Journal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
CatalystsJournal of
Submit your manuscripts athttpwwwhindawicom
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Inorganic ChemistryInternational Journal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
International Journal ofPhotoenergy
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Carbohydrate Chemistry
International Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Advances in
Physical Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom
Analytical Methods in Chemistry
Journal of
Volume 2014
Bioinorganic Chemistry and ApplicationsHindawi Publishing Corporationhttpwwwhindawicom Volume 2014
SpectroscopyInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014
Medicinal ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Chromatography Research International
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Applied ChemistryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Theoretical ChemistryJournal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Spectroscopy
Analytical ChemistryInternational Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Journal of
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Quantum Chemistry
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
Organic Chemistry International
ElectrochemistryInternational Journal of
Hindawi Publishing Corporation httpwwwhindawicom Volume 2014
Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014
CatalystsJournal of
