Electrooxidation of Indomethacin at Multiwalled Carbon Nanotubes-Modified GCE and Its Determination in Pharmaceutical Dosage Form and Human Biological Fluids

Research ArticleElectrooxidation of Indomethacin at Multiwalled CarbonNanotubes-Modified GCE and Its Determination inPharmaceutical Dosage Form and Human Biological Fluids

Sanjeevaraddi R Sataraddi Shreekant M Patil Atmanand M BagojiVijay P Pattar and Sharanappa T Nandibewoor

Post Graduate Department of Studies in Chemistry Karnatak University Dharwad 580 003 India

Correspondence should be addressed to Sharanappa T Nandibewoor stnandibewooryahoocom

Received 31 December 2013 Accepted 19 February 2014 Published 30 March 2014

Academic Editors A Amine and S Girousi

Copyright copy 2014 Sanjeevaraddi R Sataraddi et al This is an open access article distributed under the Creative CommonsAttribution License which permits unrestricted use distribution and reproduction in any medium provided the original work isproperly cited

A simple rapid selective and sensitive electrochemical method for the direct determination of indomethacin was developedThe electrochemical behavior of indomethacin was carried at multiwalled carbon nanotube- (MWCNTs-) modified glassy carbonelectrode (GCE) The cyclic voltammetric results indicated that MWCNT-modified glassy carbon electrode remarkably enhancedelectrocatalytic activity towards the oxidation of indomethacin in slightly acidic solutions It led to a considerable improvementof the anodic peak current for indomethacin and could effectively accumulate at this electrode and produce two anodic peaks at0720V and 0991 V respectively and one reduction peak at 0183VThe electrocatalytic behavior was further exploited as a sensitivedetection scheme for the determination of indomethacin by differential-pulse voltammetry (DPV) Under optimized conditionsthe concentration range and detection limit were 02 to 60 120583M and 132 nM respectively The proposed method was successfullyapplied to determination of Indomethacine in pharmaceutical samplesThe analytical performance of this sensor has been evaluatedfor detection of analyte in human serum and urine as real samples

1 Introduction

Indomethacin (Scheme 1) 1-(p-chlorobenzoyl)-5-methoxy-2-methyl-3-indolylacetic acid (INM) a nonsteroidal anti-inflammatory drug is usually regarded as the father figurein the family of nonsteroidal agents It relieves pain andreduces inflammation and fever It is slightly more toxic butin certain circumstancesmore effective than aspirin INMhastwo additional modes of actions [1] with clinical importanceIt inhibitsmotility of polymorphonuclear leukocytes and likesalicylates uncouples oxidative phosphorylation in cartilagi-nous (and hepatic) mitochondria These additional effectsaccount as well for the analgesic and the anti-inflammatoryproperties Generally overdose in humans causes drowsinessdizziness severe headache mental confusion numbness oflimbs nausea and vomiting severe gastrointestinal bleedingand cerebral edema and cardiac arrest its fatal outcome is

seen in children For these reasons it is important to analyzeINM in real samples

The widespread use of INM and the need for clini-cal and pharmacological study require fast and sensitiveanalytical techniques to determine the presence of INMin pharmaceutical formulations and biological fluids Untilnow the most common techniques for the determination ofINM in commercial dosage form were based on spectroflu-orometric [2] phosphorimetric [3] spectrophotometric [4]preconcentration and voltammetric [5] chemometric nearinfrared spectroscopy and X-ray powder diffractometry [6]photofluorometric [7] and high-performance liquid chro-matographic (HPLC) methods [8] But these methods aretime consuming are solvent usage intensive and requireexpensive devices and maintenance The advantages of elec-troanalytical methods in analysis ofdrugs are their simplicity

Hindawi Publishing CorporationISRN Analytical ChemistryVolume 2014 Article ID 816012 9 pageshttpdxdoiorg1011552014816012

2 ISRN Analytical Chemistry

N

OMe Cl

O

CH3

CH2CO2H

Scheme 1 Chemical structure of indomethacin

high sensitivity low cost and relatively short analysis time ascompared to the other routine analytical techniques

Carbon nanotubes (CNTs) continue to receive remark-able attention in electrochemistry [9 10] Since their dis-covery by Iijima [11] in 1991 using transmission electronmicroscopy CNTs have been the subject of numerous inves-tigations in chemical physical and material areas due totheir novel structural mechanical electronic and chemicalproperties [12] Subtle electronic properties suggest thatCNTs have the ability to promote charge transfer reactionswhen used as an electrode [13]Themodification of electrodesurfaces with multiwalled carbon nanotubes (MWCNTs) foruse in analytical sensing has been documented to result in lowdetection limits high sensitivities reduction of over poten-tials and resistance to surface fouling MWCNTs have beenintroduced as electrocatalysts [14ndash16] and CNTs-modifiedelectrodes have been reported to give super performance inthe study of a number of biological species [17]

To the best of our knowledge electrochemical behaviorand determination of INM in pharmaceuticals and biologi-cal fluids at multiwalled carbon nanotubes-modified glassycarbon electrode have not been reported yet The objectiveof the present work is to develop a convenient and sensitivemethod for the determination of INM based on the unusualproperties of MWCNTs-modified glassy carbon electrodeThe ability of the modified electrode for voltammetricresponse of selected compound was evaluated Finally thismodified electrode was used for the analysis of INM inpharmaceutical samples urine samples and human serumsamples The resulted biosensor exhibited high sensitivityrapid response good reproducibility and freedom of otherpotentially interfering species

2 Experimental

21 Reagents Pure INM was obtained from Sigma-AldrichIndia and used as received A stock solution of 1 times 10minus3Mwas made in double distilled water and little alkali was addedto get clear solution Multiwalled carbon nanotubes wereprocured from Sigma-Aldrich (gt90 10ndash15 nm ID 2ndash6 nm length 01ndash10 120583m) The phosphate buffers from pH 30to 1020 were prepared in doubly distilled water as describedby Christian and Purdy [18] The tablets with brand nameMicrocid (Ms Micro labs Ltd India) were purchased fromlocal market Other reagents used were of analytical orchemical grade and their solutionswere preparedwith doublydistilled water

22 Apparatus Electrochemical measurements were carriedout on a CHI1110A electrochemical analyzer (CH InstrumentCompany USA) coupled with a conventional three-electrodecell A three-electrode cell was used with a AgAgCl asreference electrode a Pt wire as counterelectrode and aglassy carbon electrode with a diameter of 2mm (modifiedand unmodified) These were used as working electrodesrespectively All the used electrodes were obtained from CHICo and all the potentials in this paper are given against theAgAgCl (3MKCl) The pH of solution was measured withan Elico LI120 pH meter (Elico Ltd India)

23 Preparation of MWCNTs-Modified Electrode Multi-walled carbon nanotubes were refluxed in the mixture ofconcentrated H

2

SO4

and HNO3

(1 3) for 4-5 h then washedwith doubly distilled water and dried in vacuum at roomtemperature The MWCNTs suspension was prepared bydispersing 2mg MWCNTs in 10mL of acetonitrile usingultrasonic agitation to obtain a relative stable suspensionTheGCEwas carefully polishedwith 030 and 005 120583M 120572-aluminaslurry on a polishing cloth and then washed in an ultrasonicbath of methanol and water respectively The cleaned GCEwas coated by casting 15 120583L of the black suspension ofMWCNT and dried in the air The electroactive areas of theMWCNT-modified GCE and the bare GCE were obtained bycyclic voltammetry (CV) using 10mMK

3

Fe(CN)6

as a probeat different scan rates For a reversible process the Randles-Sevcik formula [19] has been used as follows

119894pa = (269 times 105

) 11989932

119860119863119877

12Co ]12 (1)

where 119894pa referred to the anodic peak current 119899 is the numberof electrons transferred119860 is the surface area of the electrode119863119877

is the diffusion coefficient ] is the scan rate and Co isthe concentration of K

3

Fe(CN)6

For 10mMK3

Fe(CN)6

in01MKCl electrolyte 119899 = 1 119863

119877

= 76 times 10minus6 cm2 sminus1 then

from the slope of the plot of 119894pa versus ]12 relation theelectroactive area was calculated In bare GCE the electrodesurface area was found to be 00586 cm2 and for MWCNT-modified GCE the surface area was nearly 30ndash350 timesgreater

24 Analytical Procedure The MWCNT-modified GCE wasfirst activated in phosphate buffer (pH 60) by cyclic voltam-metric sweeps between 0 and 14V until stable cyclic voltam-mograms were obtained Then electrode was transferredinto another 10mL of phosphate buffer (pH 60) containingproper amount of INM After accumulating for 180 s at opencircuit under stirring and following quiet for 10 s potentialscan was initiated and cyclic voltammograms were recordedbetween +02 and +14 with a scan rate of 50mVsminus1 Allmeasurements were carried out at room temperature of 25 plusmn01∘C

25 Tablet Assay Procedure Ten pieces of INM tablets werepowdered in a mortar A portion equivalent to a stocksolution of a concentration of about 10mM was accuratelyweighed and transferred into a 100mL calibrated flask and

ISRN Analytical Chemistry 3

diluted with double distilled water The content of the flaskwas sonicated for complete dissolution Appropriate solu-tions were prepared by taking suitable aliquots of the clearsupernatant liquid and diluting them with phosphate buffersolutions Each solution was transferred to the voltammetriccell and analyzed by standard addition method To study theaccuracy of the proposed method and to check the inter-ferences from excipients used in the dosage form recoveryexperiments were carried outThe concentration of INMwascalculated using standard addition method

26 Recovery Studies in Spiked Human Serum Sample Serumsamples obtained from healthy individuals (after havingobtained their written consent) were stored frozen untilassay The type and amount of solvent for protein precipi-tating were optimized by recording the voltammograms ofspiked serum solutions After gentle thawing an aliquotvolume of sample was fortified with INM dissolved in doubledistilled water to achieve final concentration of 10 times 10minus3Mand treated with 05mL of acetonitrile as serum proteinprecipitating agent and then the volume was completed to2mL with the same serum sample Then it was centrifuged10 min at 4000 rpm to get rid of protein residues and uppersupernatant liquid was transferred in the voltammetric cellcontaining phosphate buffer as supporting electrolyte leavingbehind residue Voltammograms were recorded in pureacetonitrile and methanol as a serum protein precipitatingagents Also different amounts of acetonitrile were triedThebest results were obtained with 05mL acetonitrile

3 Results and Discussion

31 Cyclic Voltammetric Behavior of INM The cyclic voltam-mograms of INM at (a) blank CVs of MWCNT-modifiedGCE (b) bare CVs of MWCNT-modified GCE (c) andMWNCTS-modified GCE were shown in Figure 1 It canbe seen that the oxidation peak at the bare GCE was weakand broad due to slow electron transfer while the responsewas considerably improved at the MWCNT-modified GCEAt the bare GCE the peak was at about 0817 V but onthe MWCNT-modified GCE the peaks appeared at about0720V and 0991 VThis was attributed to the electrocatalyticeffect caused by MWCNTs

The reduction peak was observed in the reverse scan at0182V but the condition for reversible process was (119864

119901

minus

11986411990112

) = 59nmV but we got these values lesser and hencewe considered that electrochemical reaction was a totallyirreversible process The voltammograms corresponding tothe first anodic cycle and peak A were generally recordedPeak A was more intense than peak B

32 Influence of pH The electrode reactionmight be affectedby the pH of the medium The electrooxidation of 10 times10minus3M INM was studied over the pH range 30ndash102 in

phosphate buffer solution by cyclic voltammetry At pH 3one oxidation and one reduction peak appeared and at pH5 two oxidation peaks and one reduction peak appearedsharply The results showed that maximum peak current was

minus32

minus24

minus16

minus08

00

08

16

24

32

0 02 04 06 08 10 12 14

Curr

ent (120583

A)

Potential (V)

A

B

C

ab

c

Figure 1 Cyclic voltammograms of 10mM INM on MWCNT-modified GCE (a) Blank CVs of MWCNT-modified GCE (b)BareCVs ofMWCNT-modifiedGCE (c)MWNCTS-modifiedGCEScan rate 50mVsminus1 supporting electrolyte 02M phosphate bufferwith pH 60 accumulation time 180 s (at open circuit) volume ofMWCNTs suspension 15120583L

minus32

minus24

minus16

minus08

00

08

0 02 04 06 08 10 12 14

Curr

ent (120583

A)

Potential (V)

a

b

c

d

e

Figure 2 Influence of pH on the shape of anodic peak pH 30(a) 50 (b) 60 (c) 70 (d) and 100 (e) Other conditions are as inFigure 1

obtained in phosphate buffer with pH 60 (Figure 2) Hencewe selected pH 60 for remaining studies Within the rangeof pH 30 to 60 peak current (Figure 3(a)) dramaticallyincreased Above pH 6 the peak current decreased Thepeak potential was pH dependent from pH 50 after andbefore peak potential was almost pH dependent as shown inFigure 3(b)

33 Influence of Scan Rate Useful information involvingelectrochemical mechanism could be acquired from therelationship between peak current and scan rate Thereforethe electrochemical behavior of INM at different scan rates


03

04

05

06

07

08

09

1

11

12

2 4 6 8 10

A

B

pH

Ep

(V)

(a)

pH

0

05

1

15

2

2 4 6 8 10

B

A

I p(120583

A)

(b)

Figure 3 (a) Influence of pH on the peak potential of INM for peaks A and B Other conditions are as in Figure 1 (b) Variation of peakcurrents of peaks A and B with pH Other conditions are as in Figure 1

minus80

minus60

minus40

minus20

0

20

40

0 02 04 06 08 10 12 14

Curr

ent (120583

A)

Potential (V)

abcde

f

Figure 4 Cyclic voltammograms of 10 120583M INM on MWCNT-modified GCE with different scan rates (a) to (f) were 10 50 100150 200 and 300mVsminus1 respectively Other conditions are as inFigure 1

10 to 300mVsminus1 (Figure 4) was studied There was a goodlinear relationship between peak current and scan rate Theequations representing were 119868

119901

= 1567] + 2291 119903 = 0990119868119901

= 1033] + 2031 119903 = 0983 and 119868119901

= 6465] + 1382119903 = 0967 for peak A peak B and peak C respectively asshown in Figure 5 In addition there was a linear relationbetween log 119868

119901

and log ] corresponding to the followingequations log 119868

119901

= 0315 log ] + 0950 119903 = 0947 log 119868119901

=

0272 log ]+0803 119903 = 0961 and log 119868119901

= 0269 log ]+0619119903 = 0978 as shown in Figure 6 The slopes of peak A peakB and peak C were 0315 0272 and 0269 and were veryclose to the theoretically expected value of 05 for a diffusion-controlled process [20]

0

1

2

3

4

5

6

7

8

0 01 02 03

A

B

CI p(120583

A)

(V sminus1)

Figure 5 Dependence of the oxidation peak current of peaks A andB on the scan rate

The peak potential shifted to more positive values withincreasing scan rates The linear relation between peakpotential and the logarithm of scan rate could be expressed as119864119901

= 0817 + 0048 log ] 119903 = 0900 119864119901

= 0062 + 1074 log ]119903 = 0905 and 119864

119901

= 0129 minus 0045 log ] 119903 = 0910 for thepeaks A B and C respectively (Figure 7)

For irreversible electrode process according to Laviron[21] 119864

119901

is defined by the following equation

119864119901

= 1198640

1015840

+ (2303119877119879

120572119899119865) log(119877119879119896

0

120572119899119865) + (2303119877119879

120572119899119865) log ]

(2)


Table 1 Recovery test of INM in tablets

Added (M) Found (M)a Recovery () SD plusmn RSD ()30 times 10minus6 298 times 10minus6 9933 0064 plusmn 004550 times 10minus6 502 times 10minus6 1004 0299 plusmn 020780 times 10minus6 789 times 10minus6 10139 0085 plusmn 006110 times 10minus5 0998 times 10minus5 9909 0268 plusmn 019230 times 10minus5 3102 times 10minus5 1034 0629 plusmn 044550 times 10minus5 4989 times 10minus5 9978 0760 plusmn 026180 times 10minus5 8021 times 10minus5 10026 0320 plusmn 0652aAverage of five determinations

0

02

04

06

08

1

12

14

16

18

2

0

BA

C

minus2 minus15 minus1 minus05

log (V sminus1)

logI p

(120583A

)

Figure 6 Dependence of the logarithm of peak current on loga-rithm of scan rate for peaks A and B

Table 2 Influence of potential Interferents on the voltammetricresponse of 10 times 10minus5 M INM

Samples Interferents Concentration(10 times 10minus4M)

Signal change()

1 Glucose 10 +4232 Starch 10 +2613 Sucrose 10 +4454 Citric acid 10 minus2845 Magnesium stearate 10 +6686 Talk 10 +5367 Gum acacia 10 +0328 Ascorbic acid 10 +9399 Lactic acid 10 +63910 Tartaric acid 10 +67911 Oxalic acid 10 +109

where 120572 was the transfer coefficient 1198960 the standard het-erogeneous rate constant of the reaction 119899 the number of

0

02

04

06

08

1

12

C

B

A


log (V sminus1 )

Ep

(V)

Figure 7 Relationship between peak potential and logarithm ofscan rates for the peaks A and B

electrons transferred ] the scan rate and 1198640 is the formalredox potential Other symbols had their usual meaningsThus the value of 120572119899 could be easily calculated from the slopeof 119864119901

versus log ] In this system for peak A the slope was0048 taking119879 = 298119877 = 8314 and119865 = 96480 and120572nwascalculated to be 123 According to Bard and Faulkner [22]

120572 =477

119864119901

minus 1198641199012

mV (3)

where 1198641199012

was the potential where the current was at halfthe peak value So from this we had got the value of 120572 tobe 07061 Further the number of electrons (119899) transferredin the electrooxidation of INM was calculated to be 1742sim2The value of 119896119900 could be determined from the intercept ofthe above plot if the value 119864119900 was known The value of 119864119900in (2) can be obtained from intercept 119864

119901

versus ] curve byextrapolating to the vertical axis at ] = 0 [23] For peak A theintercept for 119864

119901

versus log ] plot was 0817 119864119900 was obtainedto be 08403 and the 119896119900 was calculated to be 16821 times 103 sminus1


Table 3 Determination of INM in urine samples

Sample Spiked (10minus5M) Founda (10minus5M) Recovery () SD plusmn RSD ()1 04 0403 1003 0019 plusmn 00142 06 0589 986 0017 plusmn 00123 08 0768 975 0015 plusmn 00114 20 2004 1002 0036 plusmn 00265 40 4105 1026 0155 plusmn 0109aAverage of five determinations

Table 4 Results obtained for INM analysis from spiked human serum sample

Sample Indomethacin (M) Level determineda (M) Recovery () RSD ()1 8 times 10minus5 799 times 10minus5 9991 1052 6 times 10minus5 604 times 10minus5 10047 0743 3 times 10minus5 295 times 10minus5 9950 067aAverage of five determinations

minus20

minus18

minus16

minus14

minus12

minus10

minus08

040 050 060 070 080 090 100

Curr

ent (120583

A)

Potential (V)

a

b

c

d

e

f

Figure 8 Differential-pulse voltammograms of MWCNT-modifiedGCE in INM solution at different concentrations 02 (1) 10 (2) 20(3) 40 (4) 60 (5) and 80 (6) 120583M

Similarly for the peak B n was found to be 0818 asymp1 k119900 was 17127 times 103 sminus1 also for the peak C 119899 was foundto be 08378 asymp 1 and k119900 was 113 times 10minus3 sminus1

34 Mechanism The INM contained indole moiety withthree substituent groups OCH

3

CH2

COOH and CH3

ACH3

site for electrooxidation took place for peak A Methylgroup simultaneously lost two protons and two electronsand the indole substituent alcohol was formed which onreduction of the INM was formed as shown in Scheme 2The second site for the oxidation was at CH

2

COOH Due tothe loss of a proton and electron a 3-substituted alcohol wasformed which on reduction of a methyl group gets attachedto the molecule as shown in Scheme 3

1

11

12

13

14

15

16

17

18

19

2

0 2 4 6 8 10

Curr

ent (120583

A)

INM (120583M)

Figure 9 Plot of the peak current against the concentration of INM

35 Calibration Curve In order to develop a voltammetricmethod for determining the drug we selected differential-pulse voltammetric mode because the peaks were sharperand better defined at lower concentration of INM than thoseobtained by cyclic voltammetry with a lower backgroundcurrent resulting in improved resolution According to theobtained results it was possible to apply this technique tothe quantitative analysis The phosphate buffer solution ofpH 60 was selected as supporting electrolyte for the quan-tification as it gave maximum peak current at pH 60 Thepeak at about 0717V the differential-pulse voltammogramsobtained showed that the peak current increased linearlywith increase in concentration of INM as shown in Figure 8Using the optimum conditions described above linear cali-bration curve was obtained for INM in the range of 02 to60 120583M (Figure 9) the linear equation was 119868

119901

(120583A) = 0113119862 +1117 (119903 = 0987 119862 is in 120583M) Deviation from linearity


N

OMe

O

Cl

N

OMe

O

Cl

N

OMe

O

Cl

N

OMe

O

Cl

NO

Cl

N

C H2O HOMe

O

Cl

N

C H3OMe

O

Cl

HCO

C H

Reduction

CH3

CH2CO2H

CH2CO2H

CH2CO2H

CH2CO2H

CH2CO2HCH2CO2H

CH2CO2H

minus[O]

minusH+

minusH+

H2O

minuseminus

minuseminus

CminusH2

minusC

∙H ∙

CH2

Scheme 2 Probable mechanism for the oxidation and reduction of INM for peak A

N

OMe

O

Cl

N

OMe

O

Cl

N

OMe

O

Cl

N

OMe

O

Cl

N

OMe

O

Cl

N

OMe

O

Cl

Reduction

C∙

H2 C∙

H2COO

CH3 CH3

CH3CH3

CH3

CH3

CH3

minuseminus

CH2COOH CH2COO+H

minusH+

minusCO2

H2O

CH2OH

+H+

minus[O]

Scheme 3 Probable mechanism for the oxidation and reduction of INM for peak B


was observed for more concentrated solutions due to theadsorption of INM or its oxidation product on the electrodesurface Related statistical data of the calibration curves wereobtained from the five different calibration curves The limitof detection (LOD) and quantification (LOQ) were 132 nMand 442 nM respectivelyTheLODandLOQwere calculatedusing the following equations

LOD = 3 119904119898 LOQ = 10 119904

119898 (4)

where 119904was the standard deviation of the peak currents of theblank (five runs) and119898was the slope of the calibration curve

In order to study the reproducibility of the electrodepreparation a 10 times 10minus5M INM solution was measuredwith the same electrode (renewed every time) for everyseveral hours within day and RSD of the peak currentwas 024 (number of measurements = 5) As to thebetween reproducibility it was similar to that of withinday if the temperature was kept almost unchanged Owingto the adsorption of INM or its oxidative products ontothe electrode surface the current response of the modifiedelectrode would decrease after successive use In this case theelectrode should be modified again

36 Tablet Analysis In order to evaluate the applicability ofthe proposed method in the pharmaceutical sample analysisone commercial medicinal sample containing INM was usedas to detect INM in tablets (50mg per tablet) The procedurefor the tablet analysis was followed as described in theprocedural Section 25 The detected content was 4986mgper tablet with 972 recovery

The recovery tests of INM ranging from 30times 10minus6 to 80times10minus5M was performed using cyclic voltammetry Recoverystudies were carried out after the addition of known amountof the drug to various preanalyzed formulations of INMTheresults are listed in Table 1The recoveries in different sampleswere found to lie in the range from 9909 to 1034 and thestandard deviation and relative standard deviation are listedin Table 1

37 Interference The tolerance limit was defined as themaximum concentration of the interfering substance thatcaused an error less than plusmn5 for determination of INMUnder the optimum experimental conditions the effectsof potential interferents on the voltammetric response of10 times 10minus5M INM were evaluated The experimental results(Table 2) showed that hundredfold excess of glucose starchsucrose citric acid and gum acacia did not interfere with thevoltammetric signal of INM However magnesium stearatetalk ascorbic acid lactic acid tartaric acid and oxalic acidhad apparent influence on the voltammetric signal of INM

4 Detection of INM in Urine Samples

The developed cyclic voltammetric method for the determi-nation INM in urine samplesThe recoveries from urine weremeasured by spiking drug-free urine with known amountsof INM The urine samples were diluted 100 times with the

minus18

minus16

minus14

minus12

minus10

minus08

minus06

minus04

minus02

0

04 06 08 10 12 14Cu

rren

t (120583

A)

Potential (V)

1

2

3

4

Figure 10 DPV obtained for the determination of indomethacinin human serum samples (1) blank serum extract (2) extractcontaining 30 times 10minus5M indomethacin (3) extract containing 60 times10minus5M indomethacin and (4) extract containing 80 times 10minus5

phosphate buffer solution before analysis without furtherpretreatments A quantitative analysis could be carried outby adding the standard solution of INM into the detectingsystemof urine sampleThe calibration graphwas used for thedetermination of spiked INM in urine samplesThe detectionresults of five urine samples obtained were listed in Table 3The recovery determined was in the range from 975 to10263 and the standard deviation and relative standarddeviation are listed in Table 3

41 Determination of INM in Spiked Serum Samples Thepossibility of applying the proposed method for the determi-nation of INM in human serum was tested Serum sampleswere spiked with INM to achieve final concentrations of80 times 10minus5 60 times 10minus5 and 30 times 10minus5M The amount ofINM in human serum was calculated from the related linearregression equations (Table 4) TypicalDPV curves examinedin serum are reported in Figure 10 The generally poorselectivity of voltammetric techniques could pose difficul-ties in the analysis of biological samples which containedoxidizable substances As could be seen from Figure 8 nooxidation of compounds present in serum occurred wherethe analytical peak appeared The percentage recovery ofINM was determined by comparing the peak currents ofknown amount of drug concentrations in serum with theirequivalents in related calibration curves The results of theseanalyses are summarized in Table 4 Good recoveries of INMwere achieved from this type of matrix Analysis of serum


samples by DPV involved only protein precipitation and cen-trifugation no time-consuming extraction and evaporationsteps were required

5 Conclusions

Amultiwalled carbon nanotube-modified glassy carbon elec-trode has been successfully developed for electrocatalyticoxidation of INM in phosphate buffer solution When thepotential was made to move it produced two anodic peaks at0717V and 0991 V and one cathodic peak at 0183V in 02MpH 60 phosphate buffer MWCNTs showed electrocatalyticaction for the oxidation of INM characterized by the peakcurrent which was probably due to the larger surface areaof MWCNTs Suitable oxidation and reduction mechanismswere proposed The peak at about 0717V was suitable foranalysis and the peak current was linear to concentrationsover a certain range under the selected conditions This sen-sor can be used for voltammetric determination of selectedanalyte as low as 132 nM with good reproducibility Themodified electrode has been used to determine INM inpharmaceutical samples The proposed method offered theadvantages of accuracy and time-saving as well as simplicityof reagents and apparatus In addition the results obtainedin the analysis of INM in spiked human urine and serumsamples demonstrated the applicability of themethod for realsample analysis

Conflict of Interests

The authors declare that there is no conflict of interestsregarding the publication of this paper

References

[1] G W Bisits ldquoPreterm labour The present and future oftocolysisrdquo Best Practice and Research Clinical Obstetrics andGynaecology vol 21 pp 857ndash868 2007

[2] K-I Mawatari F Iinuma and M Watanabe ldquoFluorimetricdetermination of indomethacin in human serum by high-performance liquid chromatography coupledwith post-columnphotochemical reaction with hydrogen peroxiderdquo Journal ofChromatography Biomedical Applications vol 491 no 2 pp389ndash396 1989

[3] A F Arruda and A D Campiglia ldquoPhosphorimetric deter-mination of indomethacin in pharmaceutical formulationsrdquoAnalyst vol 122 no 6 pp 559ndash562 1997

[4] N Fouzia A TehseenMAmina andN Saima ldquoSpectrophoto-metric determination of indomethacin using partial least squaremethodrdquo Proceedings of the PAS Pakistan Academy of Sciencesvol 44 no 3 pp 173ndash179 2007

[5] H Kubo Y Umiguchi and T Kinoshita ldquoFluorometric deter-mination of indomethacin in serum by high performanceliquid chromatography with in-line alkaline hydrolysisrdquo Chro-matographia vol 33 no 7-8 pp 321ndash324 1992

[6] M Otsuka H Tanabe K Osaki K Otsuka and Y OzakildquoChemoinformetrical evaluation of dissolution property ofindomethacin tablets by near-infrared spectroscopyrdquo Journal ofPharmaceutical Sciences vol 96 no 4 pp 788ndash801 2007

[7] K M Jensen ldquoDetermination of indomethacin in serum byan extractive alkylation technique and gas-liquid chromatog-raphyrdquo Journal of Chromatography vol 153 no 1 pp 195ndash2021978

[8] L Novakova L Matysova L Havlıkova and P Solich ldquoDevel-opment and validation of HPLC method for determination ofindomethacin and its two degradation products in topical gelrdquoJournal of Pharmaceutical and Biomedical Analysis vol 37 pp899ndash905 2005

[9] A Merkoci ldquoNanobiomaterials in electroanalysisrdquo Electroanal-ysis vol 19 no 7-8 pp 739ndash741 2007

[10] M Trojanowicz ldquoAnalytical applications of carbon nanotubesa reviewrdquo TrAC Trends in Analytical Chemistry vol 25 no 5pp 480ndash489 2006

[11] S Iijima ldquoHelicalmicrotubules of graphitic carbonrdquoNature vol354 no 6348 pp 56ndash58 1991

[12] P M Ajayan ldquoNanotubes fromCarbonrdquoChemical Reviews vol99 no 7 pp 1787ndash1799 1999

[13] J M Nugent K S V Santhanam A Rubio and P M AjayanldquoFast electron transfer kinetics onmultiwalled carbon nanotubemicrobundle electrodesrdquo Nano Letters vol 1 no 2 pp 87ndash912001

[14] A Merkoci ldquoCarbon nanotubes in analytical sciencesrdquoMicrochimica Acta vol 152 pp 157ndash174 2006

[15] J J Gooding ldquoNanostructuring electrodes with carbon nan-otubes a review on electrochemistry and applications forsensingrdquo Electrochimica Acta vol 50 no 15 pp 3049ndash30602005

[16] C E Banks and R G Compton ldquoNew electrodes for old fromcarbon nanotubes to edge plane pyrolytic graphiterdquoAnalyst vol131 no 1 pp 15ndash21 2006

[17] G-C Zhao Z-Z Yin L Zhang and X-W Wei ldquoDirectelectrochemistry of cytochrome c on a multi-walled carbonnanotubes modified electrode and its electrocatalytic activityfor the reduction of H

2

O2

rdquo Electrochemistry Communicationsvol 7 no 3 pp 256ndash260 2005

[18] G D Christian and W C Purdy ldquoThe residual current inorthophosphate mediumrdquo Journal of Electroanalytical Chem-istry vol 3 no 6 pp 363ndash367 1962

[19] B Rezaei and S Damiri ldquoVoltammetric behavior ofmulti-walled carbon nanotubes modified electrode-hexacyanoferrate(II) electrocatalyst system as a sensor fordetermination of captoprilrdquo Sensors and Actuators B Chemicalvol 134 no 1 pp 324ndash331 2008

[20] D K Gosser Cyclic Voltammetry Simulation and Analysis ofReaction Mechanisms Wiley-VCH New York NY USA 1993

[21] E Laviron ldquoGeneral expression of the linear potential sweepvoltammogram in the case of diffusionless electrochemicalsystemsrdquo Journal of Electroanalytical Chemistry vol 101 no 1pp 19ndash28 1979

[22] A J Bard and L R Faulkner Electrochemical Methods Funda-mentals and Applications Wiley 2nd edition 2004

[23] YWu X Ji and S Hu ldquoStudies on electrochemical oxidation ofazithromycin and its interaction with bovine serum albuminrdquoBioelectrochemistry vol 64 no 1 pp 91ndash97 2004

Submit your manuscripts athttpwwwhindawicom

Hindawi Publishing Corporationhttpwwwhindawicom Volume 2014

Inorganic ChemistryInternational Journal of

Hindawi Publishing Corporation httpwwwhindawicom Volume 2014

International Journal ofPhotoenergy


Carbohydrate Chemistry

International Journal of


Journal of

Chemistry


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


The Scientific World JournalHindawi Publishing Corporation httpwwwhindawicom Volume 2014

Medicinal ChemistryInternational Journal of


Chromatography Research International


Applied ChemistryJournal of



Theoretical ChemistryJournal of


Journal of

Spectroscopy



Analytical ChemistryVolume 2014

Journal of


Quantum Chemistry


Organic Chemistry International


CatalystsJournal of

ElectrochemistryInternational Journal of



N

OMe Cl

O

CH3

CH2CO2H

Scheme 1 Chemical structure of indomethacin

high sensitivity low cost and relatively short analysis time ascompared to the other routine analytical techniques

Carbon nanotubes (CNTs) continue to receive remark-able attention in electrochemistry [9 10] Since their dis-covery by Iijima [11] in 1991 using transmission electronmicroscopy CNTs have been the subject of numerous inves-tigations in chemical physical and material areas due totheir novel structural mechanical electronic and chemicalproperties [12] Subtle electronic properties suggest thatCNTs have the ability to promote charge transfer reactionswhen used as an electrode [13]Themodification of electrodesurfaces with multiwalled carbon nanotubes (MWCNTs) foruse in analytical sensing has been documented to result in lowdetection limits high sensitivities reduction of over poten-tials and resistance to surface fouling MWCNTs have beenintroduced as electrocatalysts [14ndash16] and CNTs-modifiedelectrodes have been reported to give super performance inthe study of a number of biological species [17]

To the best of our knowledge electrochemical behaviorand determination of INM in pharmaceuticals and biologi-cal fluids at multiwalled carbon nanotubes-modified glassycarbon electrode have not been reported yet The objectiveof the present work is to develop a convenient and sensitivemethod for the determination of INM based on the unusualproperties of MWCNTs-modified glassy carbon electrodeThe ability of the modified electrode for voltammetricresponse of selected compound was evaluated Finally thismodified electrode was used for the analysis of INM inpharmaceutical samples urine samples and human serumsamples The resulted biosensor exhibited high sensitivityrapid response good reproducibility and freedom of otherpotentially interfering species

2 Experimental

21 Reagents Pure INM was obtained from Sigma-AldrichIndia and used as received A stock solution of 1 times 10minus3Mwas made in double distilled water and little alkali was addedto get clear solution Multiwalled carbon nanotubes wereprocured from Sigma-Aldrich (gt90 10ndash15 nm ID 2ndash6 nm length 01ndash10 120583m) The phosphate buffers from pH 30to 1020 were prepared in doubly distilled water as describedby Christian and Purdy [18] The tablets with brand nameMicrocid (Ms Micro labs Ltd India) were purchased fromlocal market Other reagents used were of analytical orchemical grade and their solutionswere preparedwith doublydistilled water

22 Apparatus Electrochemical measurements were carriedout on a CHI1110A electrochemical analyzer (CH InstrumentCompany USA) coupled with a conventional three-electrodecell A three-electrode cell was used with a AgAgCl asreference electrode a Pt wire as counterelectrode and aglassy carbon electrode with a diameter of 2mm (modifiedand unmodified) These were used as working electrodesrespectively All the used electrodes were obtained from CHICo and all the potentials in this paper are given against theAgAgCl (3MKCl) The pH of solution was measured withan Elico LI120 pH meter (Elico Ltd India)

23 Preparation of MWCNTs-Modified Electrode Multi-walled carbon nanotubes were refluxed in the mixture ofconcentrated H

2

SO4

and HNO3

(1 3) for 4-5 h then washedwith doubly distilled water and dried in vacuum at roomtemperature The MWCNTs suspension was prepared bydispersing 2mg MWCNTs in 10mL of acetonitrile usingultrasonic agitation to obtain a relative stable suspensionTheGCEwas carefully polishedwith 030 and 005 120583M 120572-aluminaslurry on a polishing cloth and then washed in an ultrasonicbath of methanol and water respectively The cleaned GCEwas coated by casting 15 120583L of the black suspension ofMWCNT and dried in the air The electroactive areas of theMWCNT-modified GCE and the bare GCE were obtained bycyclic voltammetry (CV) using 10mMK

3

Fe(CN)6

as a probeat different scan rates For a reversible process the Randles-Sevcik formula [19] has been used as follows

119894pa = (269 times 105

) 11989932

119860119863119877

12Co ]12 (1)

where 119894pa referred to the anodic peak current 119899 is the numberof electrons transferred119860 is the surface area of the electrode119863119877

is the diffusion coefficient ] is the scan rate and Co isthe concentration of K

3

Fe(CN)6

For 10mMK3

Fe(CN)6

in01MKCl electrolyte 119899 = 1 119863

119877

= 76 times 10minus6 cm2 sminus1 then

from the slope of the plot of 119894pa versus ]12 relation theelectroactive area was calculated In bare GCE the electrodesurface area was found to be 00586 cm2 and for MWCNT-modified GCE the surface area was nearly 30ndash350 timesgreater

24 Analytical Procedure The MWCNT-modified GCE wasfirst activated in phosphate buffer (pH 60) by cyclic voltam-metric sweeps between 0 and 14V until stable cyclic voltam-mograms were obtained Then electrode was transferredinto another 10mL of phosphate buffer (pH 60) containingproper amount of INM After accumulating for 180 s at opencircuit under stirring and following quiet for 10 s potentialscan was initiated and cyclic voltammograms were recordedbetween +02 and +14 with a scan rate of 50mVsminus1 Allmeasurements were carried out at room temperature of 25 plusmn01∘C

25 Tablet Assay Procedure Ten pieces of INM tablets werepowdered in a mortar A portion equivalent to a stocksolution of a concentration of about 10mM was accuratelyweighed and transferred into a 100mL calibrated flask and







119901

minus

11986411990112




minus32

minus24

minus16

minus08

00

08

16

24

32

0 02 04 06 08 10 12 14

Curr

ent (120583

A)

Potential (V)

A

B

C

ab

c


minus32

minus24

minus16

minus08

00

08

0 02 04 06 08 10 12 14

Curr

ent (120583

A)

Potential (V)

a

b

c

d

e





03

04

05

06

07

08

09

1

11

12

2 4 6 8 10

A

B

pH

Ep

(V)

(a)

pH

0

05

1

15

2

2 4 6 8 10

B

A

I p(120583

A)

(b)


minus80

minus60

minus40

minus20

0

20

40

0 02 04 06 08 10 12 14

Curr

ent (120583

A)

Potential (V)

abcde

f



119901

= 1567] + 2291 119903 = 0990119868119901

= 1033] + 2031 119903 = 0983 and 119868119901


119901


119901

= 0315 log ] + 0950 119903 = 0947 log 119868119901

=

0272 log ]+0803 119903 = 0961 and log 119868119901


0

1

2

3

4

5

6

7

8

0 01 02 03

A

B

CI p(120583

A)

(V sminus1)



= 0817 + 0048 log ] 119903 = 0900 119864119901

= 0062 + 1074 log ]119903 = 0905 and 119864

119901



119901


119864119901

= 1198640

1015840

+ (2303119877119879

120572119899119865) log(119877119879119896

0

120572119899119865) + (2303119877119879

120572119899119865) log ]

(2)




0

02

04

06

08

1

12

14

16

18

2

0

BA

C


log (V sminus1)

logI p

(120583A

)




Signal change()



0

02

04

06

08

1

12

C

B

A


log (V sminus1 )

Ep

(V)




120572 =477

119864119901

minus 1198641199012

mV (3)

where 1198641199012


119901


119901







minus20

minus18

minus16

minus14

minus12

minus10

minus08

040 050 060 070 080 090 100

Curr

ent (120583

A)

Potential (V)

a

b

c

d

e

f




3

CH2

COOH and CH3

ACH3


2


1

11

12

13

14

15

16

17

18

19

2

0 2 4 6 8 10

Curr

ent (120583

A)

INM (120583M)



119901



N

OMe

O

Cl

N

OMe

O

Cl

N

OMe

O

Cl

N

OMe

O

Cl

NO

Cl

N

C H2O HOMe

O

Cl

N

C H3OMe

O

Cl

HCO

C H

Reduction

CH3

CH2CO2H

CH2CO2H

CH2CO2H

CH2CO2H

CH2CO2HCH2CO2H

CH2CO2H

minus[O]

minusH+

minusH+

H2O

minuseminus

minuseminus

CminusH2

minusC

∙H ∙

CH2


N

OMe

O

Cl

N

OMe

O

Cl

N

OMe

O

Cl

N

OMe

O

Cl

N

OMe

O

Cl

N

OMe

O

Cl

Reduction

C∙

H2 C∙

H2COO

CH3 CH3

CH3CH3

CH3

CH3

CH3

minuseminus

CH2COOH CH2COO+H

minusH+

minusCO2

H2O

CH2OH

+H+

minus[O]




LOD = 3 119904119898 LOQ = 10 119904

119898 (4)








minus18

minus16

minus14

minus12

minus10

minus08

minus06

minus04

minus02

0

04 06 08 10 12 14Cu

rren

t (120583

A)

Potential (V)

1

2

3

4






5 Conclusions




References


















2

O2

















Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy




Journal of


Quantum Chemistry




CatalystsJournal of









119901

minus

11986411990112




minus32

minus24

minus16

minus08

00

08

16

24

32

0 02 04 06 08 10 12 14

Curr

ent (120583

A)

Potential (V)

A

B

C

ab

c


minus32

minus24

minus16

minus08

00

08

0 02 04 06 08 10 12 14

Curr

ent (120583

A)

Potential (V)

a

b

c

d

e





03

04

05

06

07

08

09

1

11

12

2 4 6 8 10

A

B

pH

Ep

(V)

(a)

pH

0

05

1

15

2

2 4 6 8 10

B

A

I p(120583

A)

(b)


minus80

minus60

minus40

minus20

0

20

40

0 02 04 06 08 10 12 14

Curr

ent (120583

A)

Potential (V)

abcde

f



119901

= 1567] + 2291 119903 = 0990119868119901

= 1033] + 2031 119903 = 0983 and 119868119901


119901


119901

= 0315 log ] + 0950 119903 = 0947 log 119868119901

=

0272 log ]+0803 119903 = 0961 and log 119868119901


0

1

2

3

4

5

6

7

8

0 01 02 03

A

B

CI p(120583

A)

(V sminus1)



= 0817 + 0048 log ] 119903 = 0900 119864119901

= 0062 + 1074 log ]119903 = 0905 and 119864

119901



119901


119864119901

= 1198640

1015840

+ (2303119877119879

120572119899119865) log(119877119879119896

0

120572119899119865) + (2303119877119879

120572119899119865) log ]

(2)




0

02

04

06

08

1

12

14

16

18

2

0

BA

C


log (V sminus1)

logI p

(120583A

)




Signal change()



0

02

04

06

08

1

12

C

B

A


log (V sminus1 )

Ep

(V)




120572 =477

119864119901

minus 1198641199012

mV (3)

where 1198641199012


119901


119901







minus20

minus18

minus16

minus14

minus12

minus10

minus08

040 050 060 070 080 090 100

Curr

ent (120583

A)

Potential (V)

a

b

c

d

e

f




3

CH2

COOH and CH3

ACH3


2


1

11

12

13

14

15

16

17

18

19

2

0 2 4 6 8 10

Curr

ent (120583

A)

INM (120583M)



119901



N

OMe

O

Cl

N

OMe

O

Cl

N

OMe

O

Cl

N

OMe

O

Cl

NO

Cl

N

C H2O HOMe

O

Cl

N

C H3OMe

O

Cl

HCO

C H

Reduction

CH3

CH2CO2H

CH2CO2H

CH2CO2H

CH2CO2H

CH2CO2HCH2CO2H

CH2CO2H

minus[O]

minusH+

minusH+

H2O

minuseminus

minuseminus

CminusH2

minusC

∙H ∙

CH2


N

OMe

O

Cl

N

OMe

O

Cl

N

OMe

O

Cl

N

OMe

O

Cl

N

OMe

O

Cl

N

OMe

O

Cl

Reduction

C∙

H2 C∙

H2COO

CH3 CH3

CH3CH3

CH3

CH3

CH3

minuseminus

CH2COOH CH2COO+H

minusH+

minusCO2

H2O

CH2OH

+H+

minus[O]




LOD = 3 119904119898 LOQ = 10 119904

119898 (4)








minus18

minus16

minus14

minus12

minus10

minus08

minus06

minus04

minus02

0

04 06 08 10 12 14Cu

rren

t (120583

A)

Potential (V)

1

2

3

4






5 Conclusions




References


















2

O2

















Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy




Journal of


Quantum Chemistry




CatalystsJournal of




03

04

05

06

07

08

09

1

11

12

2 4 6 8 10

A

B

pH

Ep

(V)

(a)

pH

0

05

1

15

2

2 4 6 8 10

B

A

I p(120583

A)

(b)


minus80

minus60

minus40

minus20

0

20

40

0 02 04 06 08 10 12 14

Curr

ent (120583

A)

Potential (V)

abcde

f



119901

= 1567] + 2291 119903 = 0990119868119901

= 1033] + 2031 119903 = 0983 and 119868119901


119901


119901

= 0315 log ] + 0950 119903 = 0947 log 119868119901

=

0272 log ]+0803 119903 = 0961 and log 119868119901


0

1

2

3

4

5

6

7

8

0 01 02 03

A

B

CI p(120583

A)

(V sminus1)



= 0817 + 0048 log ] 119903 = 0900 119864119901

= 0062 + 1074 log ]119903 = 0905 and 119864

119901



119901


119864119901

= 1198640

1015840

+ (2303119877119879

120572119899119865) log(119877119879119896

0

120572119899119865) + (2303119877119879

120572119899119865) log ]

(2)




0

02

04

06

08

1

12

14

16

18

2

0

BA

C


log (V sminus1)

logI p

(120583A

)




Signal change()



0

02

04

06

08

1

12

C

B

A


log (V sminus1 )

Ep

(V)




120572 =477

119864119901

minus 1198641199012

mV (3)

where 1198641199012


119901


119901







minus20

minus18

minus16

minus14

minus12

minus10

minus08

040 050 060 070 080 090 100

Curr

ent (120583

A)

Potential (V)

a

b

c

d

e

f




3

CH2

COOH and CH3

ACH3


2


1

11

12

13

14

15

16

17

18

19

2

0 2 4 6 8 10

Curr

ent (120583

A)

INM (120583M)



119901



N

OMe

O

Cl

N

OMe

O

Cl

N

OMe

O

Cl

N

OMe

O

Cl

NO

Cl

N

C H2O HOMe

O

Cl

N

C H3OMe

O

Cl

HCO

C H

Reduction

CH3

CH2CO2H

CH2CO2H

CH2CO2H

CH2CO2H

CH2CO2HCH2CO2H

CH2CO2H

minus[O]

minusH+

minusH+

H2O

minuseminus

minuseminus

CminusH2

minusC

∙H ∙

CH2


N

OMe

O

Cl

N

OMe

O

Cl

N

OMe

O

Cl

N

OMe

O

Cl

N

OMe

O

Cl

N

OMe

O

Cl

Reduction

C∙

H2 C∙

H2COO

CH3 CH3

CH3CH3

CH3

CH3

CH3

minuseminus

CH2COOH CH2COO+H

minusH+

minusCO2

H2O

CH2OH

+H+

minus[O]




LOD = 3 119904119898 LOQ = 10 119904

119898 (4)








minus18

minus16

minus14

minus12

minus10

minus08

minus06

minus04

minus02

0

04 06 08 10 12 14Cu

rren

t (120583

A)

Potential (V)

1

2

3

4






5 Conclusions




References


















2

O2

















Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy




Journal of


Quantum Chemistry




CatalystsJournal of






0

02

04

06

08

1

12

14

16

18

2

0

BA

C


log (V sminus1)

logI p

(120583A

)




Signal change()



0

02

04

06

08

1

12

C

B

A


log (V sminus1 )

Ep

(V)




120572 =477

119864119901

minus 1198641199012

mV (3)

where 1198641199012


119901


119901







minus20

minus18

minus16

minus14

minus12

minus10

minus08

040 050 060 070 080 090 100

Curr

ent (120583

A)

Potential (V)

a

b

c

d

e

f




3

CH2

COOH and CH3

ACH3


2


1

11

12

13

14

15

16

17

18

19

2

0 2 4 6 8 10

Curr

ent (120583

A)

INM (120583M)



119901



N

OMe

O

Cl

N

OMe

O

Cl

N

OMe

O

Cl

N

OMe

O

Cl

NO

Cl

N

C H2O HOMe

O

Cl

N

C H3OMe

O

Cl

HCO

C H

Reduction

CH3

CH2CO2H

CH2CO2H

CH2CO2H

CH2CO2H

CH2CO2HCH2CO2H

CH2CO2H

minus[O]

minusH+

minusH+

H2O

minuseminus

minuseminus

CminusH2

minusC

∙H ∙

CH2


N

OMe

O

Cl

N

OMe

O

Cl

N

OMe

O

Cl

N

OMe

O

Cl

N

OMe

O

Cl

N

OMe

O

Cl

Reduction

C∙

H2 C∙

H2COO

CH3 CH3

CH3CH3

CH3

CH3

CH3

minuseminus

CH2COOH CH2COO+H

minusH+

minusCO2

H2O

CH2OH

+H+

minus[O]




LOD = 3 119904119898 LOQ = 10 119904

119898 (4)








minus18

minus16

minus14

minus12

minus10

minus08

minus06

minus04

minus02

0

04 06 08 10 12 14Cu

rren

t (120583

A)

Potential (V)

1

2

3

4






5 Conclusions




References


















2

O2

















Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy




Journal of


Quantum Chemistry




CatalystsJournal of








minus20

minus18

minus16

minus14

minus12

minus10

minus08

040 050 060 070 080 090 100

Curr

ent (120583

A)

Potential (V)

a

b

c

d

e

f




3

CH2

COOH and CH3

ACH3


2


1

11

12

13

14

15

16

17

18

19

2

0 2 4 6 8 10

Curr

ent (120583

A)

INM (120583M)



119901



N

OMe

O

Cl

N

OMe

O

Cl

N

OMe

O

Cl

N

OMe

O

Cl

NO

Cl

N

C H2O HOMe

O

Cl

N

C H3OMe

O

Cl

HCO

C H

Reduction

CH3

CH2CO2H

CH2CO2H

CH2CO2H

CH2CO2H

CH2CO2HCH2CO2H

CH2CO2H

minus[O]

minusH+

minusH+

H2O

minuseminus

minuseminus

CminusH2

minusC

∙H ∙

CH2


N

OMe

O

Cl

N

OMe

O

Cl

N

OMe

O

Cl

N

OMe

O

Cl

N

OMe

O

Cl

N

OMe

O

Cl

Reduction

C∙

H2 C∙

H2COO

CH3 CH3

CH3CH3

CH3

CH3

CH3

minuseminus

CH2COOH CH2COO+H

minusH+

minusCO2

H2O

CH2OH

+H+

minus[O]




LOD = 3 119904119898 LOQ = 10 119904

119898 (4)








minus18

minus16

minus14

minus12

minus10

minus08

minus06

minus04

minus02

0

04 06 08 10 12 14Cu

rren

t (120583

A)

Potential (V)

1

2

3

4






5 Conclusions




References


















2

O2

















Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy




Journal of


Quantum Chemistry




CatalystsJournal of




N

OMe

O

Cl

N

OMe

O

Cl

N

OMe

O

Cl

N

OMe

O

Cl

NO

Cl

N

C H2O HOMe

O

Cl

N

C H3OMe

O

Cl

HCO

C H

Reduction

CH3

CH2CO2H

CH2CO2H

CH2CO2H

CH2CO2H

CH2CO2HCH2CO2H

CH2CO2H

minus[O]

minusH+

minusH+

H2O

minuseminus

minuseminus

CminusH2

minusC

∙H ∙

CH2


N

OMe

O

Cl

N

OMe

O

Cl

N

OMe

O

Cl

N

OMe

O

Cl

N

OMe

O

Cl

N

OMe

O

Cl

Reduction

C∙

H2 C∙

H2COO

CH3 CH3

CH3CH3

CH3

CH3

CH3

minuseminus

CH2COOH CH2COO+H

minusH+

minusCO2

H2O

CH2OH

+H+

minus[O]




LOD = 3 119904119898 LOQ = 10 119904

119898 (4)








minus18

minus16

minus14

minus12

minus10

minus08

minus06

minus04

minus02

0

04 06 08 10 12 14Cu

rren

t (120583

A)

Potential (V)

1

2

3

4






5 Conclusions




References


















2

O2

















Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy




Journal of


Quantum Chemistry




CatalystsJournal of





LOD = 3 119904119898 LOQ = 10 119904

119898 (4)








minus18

minus16

minus14

minus12

minus10

minus08

minus06

minus04

minus02

0

04 06 08 10 12 14Cu

rren

t (120583

A)

Potential (V)

1

2

3

4






5 Conclusions




References


















2

O2

















Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy




Journal of


Quantum Chemistry




CatalystsJournal of





5 Conclusions




References


















2

O2

















Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy




Journal of


Quantum Chemistry




CatalystsJournal of












Journal of

Chemistry


Advances in

Physical Chemistry



Journal of

Volume 2014














Journal of

Spectroscopy




Journal of


Quantum Chemistry




CatalystsJournal of



Electrooxidation of Indomethacin at Multiwalled Carbon Nanotubes-Modified GCE and Its Determination in Pharmaceutical Dosage Form and Human Biological Fluids

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