Electrochemical behavior of mefenamic acid at graphene oxide modified carbon paste electrode

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ScienceDirect Materials Today: Proceedings 18 (2019) 582–589

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ICN3I-2017

Electrochemical behavior of mefenamic acid at graphene oxide modified carbon paste electrode Nidhi G. Talikotia, Umesh S. Devarushib, Suresh M. Tuwarb, Nagaraj P. Shettic,*, Shweta J. Malode c a

Department of Chemistry, Kanakdas Shikshana Samiti’s Arts, Commerce and Science College, Gadag, Karnataka, India b c

Department of Chemistry, Karnatak University’s Karnatak Science College, Dharwad-580001, Karnataka, India

Electrochemistry and Materials Group, Department of Chemistry, K.L.E. Institute of Technology, Hubballi-580030, Affiliated to Visvesvaraya Technological University, Karnataka, India

Abstract Graphene oxide mixed carbon paste electrode was used to look into the electrochemical performance of bio-active drug, mefenamic acid using voltammetry technique. The outcome of effect of pH, accumulation time, concentrations, scan rate, and excipients were studied. Quantitative determination of mefenamic acid conceded using highly sensitive differential pulse voltammetric method. The detection limit was found to be 0.95 nM for the concentration range 7.0 x 10-7 M to 1.0 x 10-10 M. A possible equal number of electron and proton found mechanism of electrochemical oxidation of mefenamic acid was proposed, and activation parameters ΔH≠ = 26.56 kJ mol-1, ΔS≠ = -248.7J K-1 mol-1, Ea = 29.04 kJ mol-1 were determined. © 2019 Elsevier Ltd. All rights reserved. Selection and/or Peer-review under responsibility of International Conference on Nanotechnology: Ideas, Innovations & Initiatives-2017 (ICN:3i2017). Keywords: Graphene oxide, Modified carbon paste, Mefenamic acid, Voltammetry, Pharmaceutical samples and Atomic force microscope

* Corresponding author. Tel.: +91 9611979743; fax: 0836 – 2330688 E-mail address: [email protected]

2214-7853 © 2019 Elsevier Ltd. All rights reserved. Selection and/or Peer-review under responsibility of International Conference on Nanotechnology: Ideas, Innovations & Initiatives-2017 (ICN:3i2017).

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Introduction

Mefenamic acid (MFA), an anthranilic acid derivative belongs to non-steroidal anti-inflammatory drug class. Mainly it is used in the treatment of pain due menstrual cycles [1-2]. Longer usage of this drug originates the generation of toxic metabolites which leads to death in patients. Removal of MFA by different methods has been reported [3-9]. Owing to the significance of MFA, it becomes necessary to build up a easy, quick and consistent practice for the determination of MFA. Few reports are available on determination of MFA by spectrophotometric [10], chromatography [11], electrochemical methods using modified glassy carbon electrode [12], composite film modified electrode [13–15] etc. In all such cases by electrochemical methods for determination of MFA, the MFA was quantified up to few milli moles. Hence, we have looked in to the same methods by modifying the electrode by graphene oxide carbon paste to improve the quantification of MFA in nano scale. Further, different voltammetric techniques used to compare the results with each other for still better method. The findings are found to be optimistic in the analysis of MFA. An attempt has also been made to find out the thermodynamic parameters to understand the mechanism of electrochemical oxidation of MFA at Graphene oxide modified carbon paste electrode (GO/CPE). 2. Experimental 2.1 Apparatus and chemicals The Electrochemical behavior of MFA was carried out using electrochemical analyzer (CHI D630 Company, USA Model,) at 25.0 ± 2.0 0C consisting of 10 ml cell with three-electrode system. Carbon paste adapted graphene as working, platinum wire and Ag/AgCl (3 M KCl) as counter and reference electrode. The pH solutions ranging between 3.0 -11.2 (I = 0.2) were prepared [16] and MFA (Cipla) 1.0 mM was set in ethanol. Excipients were prepared using double distilled water. 2.2 Preparation of electrode and characterization The graphene oxide modified CPE was set by an appropriate mixing of graphite powder, graphene oxide, and paraffin oil. Further to make it a homogeneous paste agate mortar was used. The obtained paste was packed steadily into a hollow space of poly tetra fluoro ethylene tube (PTFE). Using filter paper the electrode surface is made smooth by polishing. The used paste was isolated cautiously preceding to pressing a fresh portion [17]. The area of electrode was presented by Randles-Sevcik equation [18]. The surface area was calculated to be 0.06 cm2. Further the unmodified and modified carbon paste electrodes were characterization by means of atomic force microscope analysis (AFM) in air. The topological images are shown in Fig. 1(A and B).

Fig.1. AFM images of: (A) Unmodified CPE; (B) Modified CPE.

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Results and discussion

3.1 MFA electrochemical performance MFA electrochemical performance was studied between the pH ranges 3.0 to 11.2 using cyclic voltammetry technique in phosphate buffer solution. It results in one sharp oxidation peak (Fig. 2). Both unmodified and modified paste electrode exhibits a sharp peak due to oxidation with irreversible nature. An elevated peak was observed at modified paste due to lager effective surface area of nanoparticles used as modifier makes the fast electron transfer [14, 15].

Fig. 2. CVs of 0.1 mM MFA on unmodified and modified electrode pH 6.0 PBS at a scan rate of 50 mVs-1.

3.2 pH Effect Electrochemical oxidation of MFA investigated using pH PBS ranging between 3.0 to 11.2 (Fig. 3). The upper limit peak current was attained at pH 6.0 and thus selected for further investigation [19]. Negative movement in the peak potential attained with raise in the PBS pH. The linear relationship between Ep and pH showed a slope value 30mV/pH which is close enough to the expected assessment of 29.5mV/pH denotes the contribution of two electrons in the electro-oxidation process of MFA [20-22]. Ep = -0.030 pH + 0.872; R2 = 0.996

Fig. 3. Cyclic voltammograms of MFA (0.1 mM) in PBS of varying pH= 3.0-11.2. Plot of: (A) Ip versus pH; (B) Ep versus pH.

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3.3. Effect of scan rate An electrochemical action of MFA at altering scan rates by CV technique to get information about electrochemical mechanism (Fig. 4) was considered. A linear relationship between current and scan rates showed that the present progression in inhibited by diffusion [23, 24]. Reliance of current on scan rates is articulated as follows, Ip= 69.279(ʋ) +6.710 Ip= 0.153ʋ ½ + 0.96 log Ip = 0.56 log ʋ + 0.626 It was also observed that the potential changes to more positive values with rising the scan rate, which confirms the irreversibility of the oxidation development [25, 26], and a linear correlation between potential and logarithm of scan rate is articulated by the resulting equation. Ep = 0.013 log ʋ + 0.647

Fig. 4. Cyclic voltammograms of 0.1mM MFA in pH 6.0 PBS at different scan rates: 0.02-0.4 Vs-1. Plot of; (A) Ip versus ʋ; (B) Ip versus ʋ1/2; (C) log Ip vs log ʋ; (D) Epvs log ʋ.

3.4 Probable mechanism of electro-oxidation of MFA An electrochemical oxidation of MFA at GO/CPE involves two electrons to the formation of dimer through free radical formation of MFA, which corresponds to the initial oxidation product MFA [14].

O

-e-H+

N H

OH

O OH

CH3

N CH3

CH3

CH3 H3C H3C

O

O OH

Dimerization

N OH CH3 CH3

N

O OH

OH O

CH3

CH3 CH3

N

N

CH3

A possible free radical mechanism of MFA

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3.5. Effect of Temperature The electrochemical behavior of MFA (1.0 x 10-5 M) was studied by varying temperatures between 288K to 313K at GO/CPE (Fig. 5). Oxidation peak current enlarged linearly with enhance in temperature with correlation coefficient of 0.99 (Fig. 5A). The heterogeneous rate constant value obtained using Butler-Volmer equation [27, 28]. I0 = n F k0 C0(1-α)CRα where, I0 is peak current, ko is heterogeneous rate constant, n transferred electron number, F Faraday constant, α is charge coefficient (1), CR & C0 concentration of reductant and oxidant respectively.

Fig. 5. Dependence of Ipa with temperature for 1.0 x 10-5M [MFA] at GO/CPE 288, b) 293, c) 298, d) 308 and e) 313 K Scan rate, 50 mV/s, intervals 1.0 x10-3 V and Accumulation time 2 s , pH = 6.0. (A) Plot of Peak current (Ipa) versus Temperature (K); (B) Plot of log k0 vs 1/ Temperature.

4. Analytical Applications 4.1 Variation of concentration of MFA Quantitative determination of MFA was carried out using sensitive, reliable, techniques DPV and SWV. Since, these exhibits peak at lower concentrations of an analyte. DPV (Fig. 6) & SWV (Fig. 7) were obtained with increasing amounts of [MFA] in the range of 7.0 x 10-7 M to 1.0 x 10-10 M. A linear calibration curve was attained by the plot of Ip versus [MFA] (Fig. 6A, 6B) & (Fig. 7A, 7B) [29, 30]. Based on the results obtained for peak current, Detection and quantification values were calculated (Table 1) to be DPV = 1.014 x10-10 & SWV = 1.28 x1010 . DPV Ip= 0.287 [MFA] + 9.0 x 10-8; SWV Ip = 0.407 [MFA] + 1.0 x10-9 Parameters Linearity range (nM)

Table 1. Results obtained by calibration plot of MFA DPV

SWV

700 to 0.1

700 to 0.1

LOD (nM) LOQ (nM)

1.06 3.53

0.95 3.16

Intra-day assay RSD (%)

1.8

1.5

Inter-day assay RSD (%)

2.0

1.8

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Fig. 6. DPV for increasing concentrations of MFA in at GO/CPE pH= 6.0, (a) 1.0 x 10-10-7.0 x 10-7 M. Plot of; A) Ip vs [MFA] (10-7 to 10-8 M) B) Ip vs [MFA] (10-9 to 10-10 M).

Fig. 7. SWV for increasing concentrations of MFA in at GO/CPE pH= 6.0, (a) 1.0 x 10-10-7.0 x 10-7 M. Plot of; A) Ip vs [MFA] (10-7 to 10-8 M) B) Ip vs [MFA] (10-9 to 10-10 M).

4.2 Analysis in pharmaceutical samples Tablets containing MFA ground to fine powder and dissolved in ethanol, used for analysis. The values achieved are in fine agreement with the strips content label (Table 2). A good recovery range with RSD 1.6% was obtained. Table 2. Values of characteristic calibration plot for [MFA] in pharmaceutical sample Parameters

DPV

Labeled claim (mg)

250

Amount found (mg)

246.2

Recovery (%)

98.5

LOD (nM)

2.6

LOQ (nM)

8.6

RSD (%)

1.6

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4.3 Effect of excipients The effect of excipients was evaluated for 1.0x10-5 M MFA. It was found that from the Fig. 8 that 100 folds of excipients did not interfere with the voltammetry of MFA.

Fig. 8. Interference of excipients on the voltammetry of MFA.

4.4 Comparative study The present study shows significant differences in the detection limits against reported studies with various techniques viz., GCE, GCE modified different modifiers like carbon nanotubes (CNTs)/gold nanoparticles composite, Barium doped ZnO nanoparticles, MWCNT-CHIT etc. The opted voltammetric techniques such as DPV and SWV are selective, sensitive and superior with low concentration detection. The linear relationship between current and concentrations designate that the technique is useful for MFA detection in diverse illustration. The limit of detection and quantification of MFA were calculated by the current method are with lower detection limit value, more sensitive compared with the earlier reports as listed in Table 3. This recommends the proposed sensing base serves as an efficient system for MFA detection in low concentrations. Table 3. LOD values by other methods Technique LOD (nM) GCE 15x103 GCE modified with RTIL-CHIT-MWCNT 1235 GCE modified with MWCNT-CHIT 660 CNT/gold nano particles composite film 10 GCE modified with Ba doped ZnO nanoparticles GCE modified with CNTs DPV at GO/CPE SWV at GO/CPE

6.02 69 1.06 0.95

References [31] [32] [33] [34] [15] [35] present work Present work

4.5 Urine and recovery test Human urine samples from healthy persons spiked with known quantity of the drug and were subjected to analysis. The recovery values attained range from 97.5% to 99.8 % with RSD of 2.98 % which is better than those of GCE or CPE (Table 4).

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Table 4. MFA analysis in spiked human urine samples. Urine Samples

Spiked [MFA] x 105M

Detected [MFA]x105 M

Recovery

1

0.1

0.092

97.5%

2

0.3

0.294

98.9%

3

0.6

0.596

99.2%

4

0.7

0.699

99.8%

5. Conclusions Graphene is a good conductor used as bio-sensors for bio-active organic molecules like MFA. Graphene oxide modified carbon paste electrode is characterized by AFM. An electrochemical investigation of MFA at GO/CPE was diffusion controlled involving two electrons transfer. Reaction mechanism was anticipated. The quantitative determination MFA was done using DPV and SWV techniques. The proposed sensing base serves as an efficient system for MFA detection in low concentrations. The thermodynamic parameters, good recovery values, sensitivity found in all parameters and no effect of the excipients suggests that it would be a better substitute for electro-oxidation of MFA and determination. References [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] [29] [30] [31] [32] [33] [34] [35]

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