Application of a sensitive electrochemical sensor modified with WO3 nanoparticles for the trace determination of theophylline

Microchemical Journal 149 (2019) 104005

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Application of a sensitive electrochemical sensor modified with WO3 nanoparticles for the trace determination of theophylline Seyyed Ahmad Rezvani, Ahmad Soleymanpour

T

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School of Chemistry, Damghan University, Damghan 3671641167, Iran

ARTICLE INFO

ABSTRACT

Keywords: Theophylline WO3 nanoparticles Multiwall carbon nanotubes Adsorptive stripping differential pulse voltammetry

An electrochemical sensor based on tungsten trioxide nanoparticles and multiwall carbon nanotubes composite was developed for the determination of theophylline (THP). WO3 nanoparticles were synthesized by the precipitation reaction in acidic media. The constructed sensor was applied for the quantification of theophylline by adsorptive stripping voltammetry. In order to achieve the best electrochemical response, the effects of different parameters such as scan rate, electrolyte solution conditions, pH and accumulation conditions were investigated. Under optimal statuses, the calibration curve represented a concentration linear range of 2.5 × 10−8–2.6 × 10−6 M and a low limit of detection 8.3 × 10−9 M. The sensor represented great selectivity for THP toward a wide diversity of foreign organic and inorganic chemicals. The modified sensor was used successfully for the measurement of theophylline in pharmaceutical and biological media.

1. Introduction Theophylline (THP), also known as 1,3-dimethylxanthine,is a methylated xanthine alkaloid which used to prevent and treat respiratory diseases such as wheezing, shortness of breath and tightness in the chest arising from asthma, chronic bronchitis and emphysema. It relaxes smooth muscles and opens the airway in the lungs and makes breathing easier. It is also used as an effective respiratory stimulator in the treatment of asthma and bronchospasm in adults, infant apnea, asthmatic acute phase [1], chronic obstructive pulmonary disease (COPD) [2] and emphysema [3] in adults. Theophylline has also been prescribed for the treatment of cough in patients with COPD and angiotensin-converting enzyme (ACE) inhibitor-induced cough [4]. The therapeutic plasma concentrations of THP is considered to range from 5 to 20 g mL−1 [5]. At lower levels, it may be not effective and at higher levels it may have serious side effects. Hyperactivity, decreased attention span, jitteriness and insomnia are some of the THP side effects [6]. Because theophylline naturally present in tea, soft drinks and food stuff such as cocoa and chocolate-based food products [2], it is significant to develop a precise, simple and quick procedure for the measurement of theophylline in different media. Several techniques have been applied for the quantitative determination of THP such as electrochemical methods [7–14], liquid and gas chromatography [15–19] and spectrophotometry [20,21]. While chromatographic methods represent high sensitivity and precision, they are

⁎

time-consuming and high-cost. Moreover, they limited by complex sample preparation steps and use of organic solvents. In the analysis of pharmaceutical and biological samples, electrochemical methods have been developed due to their simplicity, rapidity, low cost of equipment, high sensitivity and accurate analytical tools. With respect to these suitable characteristics for determination of different important species, many efforts have been employed to improve the modifications of electrodes for increasing the sensitivity and selectivity of the quantifications. The chemical modification of electrodes with modifiers result in significant improvement of electrochemical sensors performance. Nanostructure materials particularly multiwall carbon nanotubes (MWCNT) have devoted significant interestsdue to their unique electronic, physical and chemical characteristics which make them suitable for the design of modified electrodes in electrochemistry [9,22]. Efficient mass transport, catalytic behavior, large effective surface area, high porosity, good adsorption capacity and more active surface sites make MWCNTs as a good modifier for modification of conventional electrodes [23]. For instance, MWCNT/GCE was used for the detection and study of voltammetric behavior of phytohormone 6-benzylaminopurine [24]. Also, an electrochemical electrode based on functionalized -SWCNT–β-CD/GCE was fabricated for the trace analysis of methyl parathion in vegetable samples which represented a low detection limit of 0.4 ng mL−1 [25]. Moreover, electrochemical sensor fabricated with composite consisting of both halloysite nanotubes and carboxyl-

Corresponding author. E-mail address: [email protected] (A. Soleymanpour).

https://doi.org/10.1016/j.microc.2019.104005 Received 11 February 2019; Received in revised form 11 June 2019; Accepted 12 June 2019 Available online 15 June 2019 0026-265X/ © 2019 Elsevier B.V. All rights reserved.

Microchemical Journal 149 (2019) 104005

S.A. Rezvani and A. Soleymanpour

functionalized-MWCNTs were employed for the simultaneous determination of uric acid, guanine and adenine in biological samples [26]. Nanostructure species improve the efficiency of functional substances and provide them with some incomparable properties. Since coated nanostructured materials increase surface-to-volume ratio of the electrode surface, they supply more surface area for interface interactions. Furthermore, due to the change of surface energies, the species next to the surface have unlike bond properties than those present in the solution bulk. Finally, the quantum restriction results due to the intrinsically small size of nanomaterials, they can considerably affect the charge distribution and electronic bond structure [27]. Nanostructured WO3 is an interesting n-type semiconductor which has high surface-to-volume ratio, good chemical stability, adaptability with low pH environments and high temperatures, good biocompatibility, electrochemical redox characteristic and quantum confinement [28,29]. It is very adaptable and exhibits unique properties which make it to be most widely used functionalized metal oxide in several research area [30]. Tungsten trioxide has been used in a wide variety of applications in the field of gas sensors and biosensors [31–33], photodegradation [34], dye solar cells [35], electrochromic applications [36], lithium batteries [37], energy storage applications [38], and specially, voltammetric sensors [39,40]. Tungsten trioxide has been synthesized by various techniques such as thermal decomposition [41], colloidal process [42], ion-exchange method [43], acid precipitation [44] and chemical vapor deposition [45]. The precipitation of WO3.nH2O from a concentrated acidic solution of tungstate ion is a popular synthetic method illustrated as the following [46]:

WO24 + 2H+

H2O

H2 WO4

H2O

(MWCNT) were bought from Aldrich and used as received. THP tablets (200 mg) were supplied from Abidi Pharmaceutical Company (Tehran, Iran). Sodium tungstate dihydrate (Na2WO4.2H2O) and all other salts were obtained from Merck Company. The THP stock solution (0.02 M) was provided by the dissolving an appropriate amount of THP in double distilled water and then kept in darkness at 4 °C. Before each electrochemical measurement, highly pure nitrogen was used for solution deoxygenation during 300 s and a nitrogen flow was maintained over the solutions during the experiments. 2.3. Synthesis of WO3 nanoparticles Tungsten trioxide nanoparticles were prepared using the chemical precipitation method in acidic media [44]. A certain amount of the tungstate salt was dissolved in double distilled water and the resulting solution was brought to 80 °C. While the solution was stirring vigorously, a warm and relatively concentrated nitric acid solution was added slowly at a rate of about 0.5 mL/min. The final concentration of the tungstate salt and nitric acid in the solution was adjusted at 10 mM and 4.0 M, respectively. Simultaneously stirring the solution, the resulting mixture was kept at 80 °C for 60 min. The precipitate was then allowed to cool down and settle for 1 day at room temperature. In order to wash the precipitate, a large amount of distilled water was added and stirred for 10 min and then allowed precipitate to settle down during the night. This washing procedure was performed tree times. Finally, the precipitate was separated by decanting and dried at 100 °C. The dried precipitate was used to prepare the electrochemical sensor. 2.4. Preparation of WO3/MWCNT modified electrode

WO3 . nH2 O

The acid treatment of carbon nanotubes is very important in order to eliminate metallic impurities and appear carboxylic groups which can improve the analytical signal, facilitate the electron transfer or allow further functionalization [48]. MWCNTs were functionalized in a solution of sulfuric and nitric acid in 3:1 ratio for 5 h at ambient temperature under stirring. Then, the suspension was separated by centrifugation and solid residual was washed many times with distilled water until the washing water was neutralized and finally the solid was dried. 5.0 mg of the functionalized MWCNT and 3.0 mg WO3 nanoparticles were added to 2 mL distilled water and the mixture was sonicated for 20 min until a relative stable suspension was obtained. Before surface modification, the GCE was polished with 0.3 and then 0.05 μm alumina on polishing cloths and subjected to ultrasonic cleaning with H2SO4–H2O (50% v/v) for 10 min and finally rinsed with distilled water and ethanol, respectively. 4 μL of the above suspension was instilled directly onto the clean GCE surface and it was left to dry at ambient temperature. The constructed electrode (WO3/MWCNT/GCE) was used for subsequent analyses.

WO3alone exhibits low electronic conductivity and a limited potential window which limit its application, however, incorporation with highly conductive material such as MWCNTs improves its conductivity and the capacitive behavior of such composites also impressively increases [47]. In the present work, a sensitive electrochemical sensor for THP determination was constructed by the modification of glassy carbon electrode (GCE) with the nano-composite of tungsten trioxide nanoparticles and multiwall carbon nanotubes. The WO3 nanoparticles were synthesized by precipitation reaction between the sodium tungstate dihydrate and nitric acid based on the above mentioned equation. The modified GCE exhibit excellent response characteristics to theophylline and was used to determine THP in pharmaceutical and biological media. 2. Experimental 2.1. Apparatus

2.5. Analysis procedure

All voltammetric measurements have been carried outon an Autolab PGSTAT 30 electrochemical system (Netherlands) using NOVA software. A three-electrode system consisting modified-GCE as the working electrode, a platinum wire as the reference and an Ag/AgCl/KCl (sat,d) as the reference electrode was employed. Scanning electron microscopy (SEM) was carried out with Leo 1450VP microscope. Powder X-ray diffraction (XRD) patterns were recorded with a D8 Advance Bruker diffractometer using CuKα radiation (λ = 0.15 nm) in the 2θ range of 20–70°. The pH of solutions was controlled by an 827 pH-meter (Metrohm).

For stripping voltammetric analysis, 10 mL of sample solution containing specific amount of the analyte in sulfuric acid 0.05 M was placed into the electrochemical cell anda magnetic stirrer was applied to shake the test solution in the accumulation step. During the stirring of the solution at 400 rpm with the magnetic stirrer, an accumulation potential of +0.2 V was exerted to the modified GCE for 210 s. After the accumulation time, the stirrer was put out and after 15 s the voltammogram was obtained by scanning the potential toward the positive direction from +0.9 to +1.3 V with a sweep rate of 40 mVs−1 and the peak current was analyzed at +1.18 V for THP. The same procedure was applied to a blank solution without THP to get blank peak current.

2.2. Reagents

2.6. Preparation of real samples

All chemicals were of AR (Analytical Reagent) grade and were utilized as obtained and all of solutions were prepared with doubly distilled water. Theophylline (THP) and multiwall carbon nanotubes

For pharmaceutical formulations, two THP tablets were taken 2

Microchemical Journal 149 (2019) 104005

S.A. Rezvani and A. Soleymanpour

a b

c

d

(a)

Fig. 1. (a) The XRD pattern of WO3 nanoparticles (arrows show the reference peaks of WO3) and the reference pattern (inset), (b) the EDX image of WO3/MWCNT composite, (c) the SEM image of carbon nanotubes and (d) the SEM image of WO3/MWCNT composite.

separately, weighed and milled to a fine powder using a mortar with a pestle. Exactly a weight equal to one tablet was dissolved in doubled distilled water, sonicated for 15 min and then filtered by Whatman filter paper to remove any undissolved impurity. The filtrate was delivered to a 100 mL flask which was then filled up to the mark with doubled distilled water. Finally, from this solution a 5 μM solution of THP was prepared in H2SO4 0.05 M (as unknown sample). Aliquots of 6 mL urine sample (obtained from healthy volunteers) was transferred to a 50 mL calibrated flask, made up to the mark with H2SO4 (0.05 M) and shaken for 5 min. 5 mL of this solution was transferred into the electrochemical cell. Different amounts of THP solution were spiked into the cell separately and the voltammogram was recorded. Then, theophylline content of the solution was determined by using the standard addition method.

WO3nanoparticles was obtained using Debye–Scherrer equation from the XRD spectrum at dominant peak (2θ = 25.6) [49].

D=

k cos

where D is diameter size of the particles, k is a constant equals 1, λ is the wavelength of X-ray source (λ = 0.15 nm), β is the full width at half maximum (FWHM) and θ is the diffraction angle. The average crystallite size based on this equation was obtained equal to 32.4 nm. Scanning electron microscopy (SEM) was employed to study the morphology of the electrode surface. Fig. 1c and d represent the SEM scans of carbon nanotubes and WO3/MWCNT composites, respectively. As it is clear in the figures, WO3 nanoparticles are dispersed in carbon nanotubes. This develops the roughness of the MWCNTs [50] and increases the surface area of the modified electrode. Moreover, the energy dispersive X-ray (EDX) analysis was applied to characterize the modifier film. As shown in Fig. 1b, the EDX results exhibited that W, C and oxygen were the major elements.

3. Results and discussion 3.1. Characterization of WO3 nanoparticles X-ray diffraction analysis (XRD) was used to characterize some properties of synthesized nanoparticles. The XRD pattern is shown in Fig. 1a. By comparison with the XRD database (PANalytical X'Pert HighScore), it was found that the synthesized particles of single-walled tungsten trioxide (WO3.H2O) were crystallized in the orthorhombic crystal system. The XRD pattern of reference is also shown in Fig. 1a (inset). As seen, the relative intensities and position of main peaks are in agreement with the reference pattern. The size of the

3.2. Electrochemical behavior of THP It was known that THP is protonated in the acidic environment and oxidized by the loss of two electrons [51]. This process is shown in Fig. 2. The cyclic voltammogram of THP is shown in Fig. S1 indicating the oxidation of THP at the electrode surface is an irreversible process. 3

Microchemical Journal 149 (2019) 104005

S.A. Rezvani and A. Soleymanpour

O H N

H3C N

+ N

H2 N

H3C

+

N

Acid

O

O

O

H N

H3C H2O

N

O

H+

- 2e- - H+

N

O

CH3

O

N

N

N H

N CH3

CH3 Fig. 2. The oxidation mechanism of THP. 15

25

11

15

7

Bare GCE

10

ΔI (µA)

20

I (µA)

ΔI (µA)

12 8 4 0 3

5

7

9

11

ʋ1/2 3

MWCNT-GCE WO3/MWCNT-GCE

5

-1

0 1.05

-5

1.11

1.17

1.23

1.29

1.35

0.9

1

1.1

1.4

appears at potential of +1.18 V. The observed shift of THP oxidation potential can be due to the presence of carbon nanotubes which increase the anodic current by decreasing the electron transfer resistance and also increasing the effective surface of the electrode. On the other hand, the presence of tungsten nanoparticles in WO3/MWCNT/GCE increases the absorption of the analyte on the electrode surface which improves the anodic current.

1250

b

a

1000

Z′′ ((Ω)

1.3

Fig. 5. Cyclic voltammograms of THP (1.0 × 10−3 M) at WO3/MWCNT/GCE obtained in H2SO4 0.05 M employing various scan rates (10, 20, 30, 40, 50, 60, 70, 80, 90 and 100 mVs−1). Inset: the plot of pick current vs.ʋ1.2.

Fig. 3. Differential pulse voltammograms of THP (2.0 × 10−5 M) at various electrodes in 0.05 M H2SO4, scan rate = 40 mVs−1, accumulation potential = 0.2 V and accumulation time = 210 s.

c

1.2 E (V)

E (V)

750

3.4. Electrochemical impedance spectroscopy and effective surface area

500

Electrical behavior of the bare and modified electrodes were investigated by electrochemical impedance spectroscopy (EIS) method in 0.5 mM [Fe(CN)6]3−/[Fe(CN)6]4− and 0.05 M H2SO4 solution. The obtained Nyquist plots are shown in Fig. 4. According to Fig. 4, it is indicated that the charge transfer resistance value (Rct) of the modified WO3/MWCNT/GCE (473 Ω) is less than MWCNT/GCE (603 Ω) and also bare GCE (945 Ω) indicating the better conductivity of WO3/MWCNT which surely is due to the enhanced charge transfer rate by the increased conductivity and capacitive behavior of the composite [47]. Moreover, the calculated CPEdl (constant element illustrating the capacitance of double layer) values (756, 927 and 974 pF for GCE, MWCNT/GCE and WO3/MWCNT/GCE, respectively) represent that the effective surface of the rGO/PWA is increased. To show the increasing of the electrode surface due to the modification, the effective surface area of the bare and modified electrodes were calculated by recording the cyclic voltammetry of K3Fe(CN)6 at various scan rates and using Randles-Sevcik equation [52] as following:

250

0 0

400

800

1200

1600

2000

Z′ (Ω)

Fig. 4. Nyquist plots for GCE (a), MWCNT/GCE (b) and WO3/MWCNT/GCE (c) in 0.5 mM [Fe(CN)6]3−/[Fe(CN)6]4− and 0.05 M H2SO4 solution.

3.3. The electrochemical behavior of THP at various electrodes In order to study the ability of the modifier composite to improve the performance of the electrode, the electrochemical response of THP was investigated at various electrodes including the bare GCE, carbon nanotubes modified GCE (MWCNT/GCE) and WO3/MWCNT/GCE by differentialpulsed voltammetry technique. The resulted voltammograms are displayed in Fig. 3. At the unmodified GCE, the peak current due to the oxidation of THP is negligible and appears at potential of +1.26 V. For the MWCNT/GCE, the peak current is increased and appears at potential of +1.17 V. Finally, at the presence of WO3/ MWCNT/GCE, the peak current is more increased dramatically and

Ip = (2.69 × 105) n3/2 A D1/2

1/2C

where Ip refers to the anodic peak current in Ampere, D is diffusion coefficient of K3Fe(CN)6 (5 × 10−6 cm2/s), n is the number of transferred electrons (n = 1), ν is the scan rate (vs−1), A is the effective surface area of the electrode in cm2 and C is the concentration of K3Fe 4

Microchemical Journal 149 (2019) 104005

S.A. Rezvani and A. Soleymanpour

1.25

15

b

1.2

12

1.15

9

ΔI (µA)

E (V)

a

1.1

6

1.05

3

1

0 0

1.3

2.6

3.9

5.2

6.5

0

1.3

2.6

pH

3.9

5.2

6.5

pH

Fig. 6. The effect of electrolyte solution pH on the peak potential (a) and peak current (b) of the electro-oxidation of THP (2.0 × 10−6 M) at scan rate = 40 mVs−1, accumulation potential = 0.2 V and accumulation time = 210 s.

12

12

a

b 9

ΔI (µA)

ΔI (µA)

9

6

3

6

3

0

0 0

100

200

300

400

-0.4

-0.1

Time (s)

0.2

0.5

0.8

E (V)

Fig. 7. The effect of accumulation time (a) and potential (b) on the THP peak current at the scan rate of 40 mVs−1in the presence of 2.0 × 10−6 M THP. Table 1 Measurement of THP contents in pharmaceutical tablet and urine samples.

12.5 16

ΔI (µA)

12

ΔI (µA)

10

7.5

8

Sample

Added (μM)

Founda (μM)

Recovery (%)

t-Value (4.30)c

4

Tablet

0.000b 0.100 1.000 0.050 0.500

0.097 0.197 1.120 0.052 0.491

– 98.5 101.8 104.0 98.2

– 1.30 2.66 1.15 1.95

0 0

0.6

1.2 1.8 CTHP (µM)

2.4

3

Urine

5 a b

2.5

c

1.14

1.18

1.22

1.26

0.002 0.004 0.013 0.003 0.008

Average value of three replicate determinations. The THP concentration in the unknown sample was 0.1 μM. t-Value calculated at 95% confidence limit and two degrees of freedom.

current of the THP oxidation at the WO3/MWCNT/GCE surface was studied in a solution of 1.0 × 10−3 M THP and H2SO4 0.05 M by cyclic voltammetry. The obtained voltammograms are shown in Fig. 5. It is concluded that with the increasing of scan rates from 10 to 100 mVs−1, the oxidation peak current also enhanced. The resulted peak currents were proportional to the square root of scan rates (ʋ1/2) in the range of 10–100 mV.s−1 (inset graph) indicating the oxidation process was diffusion controlled. The equation of linear regression was I (μA) = 1.267ʋ1/2–3.3837 (R2 = 0.9936).

0 1.1

± ± ± ± ±

1.3

E (V)

Fig. 8. AdSDPV curves obtained for different concentrations of THP (2.6, 2.1, 1.9, 1.4, 1.1, 0.6, 0.3, 0.125, 0.075, 0.05 and 0.025 μM) at WO3/MWCNT/GCE obtained in H2SO4 = 0.05 M at scan rate = 40 mVs−1 and modulation amplitude 50 mV. Inset: Calibration plot for concentration ranges of THP from 2.5 × 10−8 to 2.6 × 10−6 M.

(CN)6 (mol/cm3). The surface area can be obtained from the slope of the Ip versus ν1/2 plot. The resulted effective surfaces were equal to 0.091 cm2, 0.058 cm2 and 0.037 cm2 for the WO3/MWCNT/GCE, MWCNT/GCE and bare-GCE, respectively. The results showed that the active surface area of the WO3/MWCNT/GCE increased significantly by a confident of 2.5 times compared to the bare GCE indicating the higher electrochemical activity of the modified electrode.

3.6. Effect of pH To investigate the relationship between pH and peak potential, the supporting solutions with different pH (0.7–6.0) were prepared by addition a certain volume of NaOH solution into 0.2 M H2SO4 solution. In this pH range, a linear dependence was observed between the peak potentials and pH (Fig. 6a) with a regression equation equal to Epa(V) = −0.0289pH + 1.228 (R2 = 0.994). The slope of 28.9 mV pH −1 confirms an oxidation mechanism including the transference of one proton and two electrons in accordance with the represented

3.5. The scan rate effect The effect of potential sweep rate on the peak potential and peak 5

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S.A. Rezvani and A. Soleymanpour

Table 2 Analytical performance comparison of the WO3/MWCNT/GCE sensor with some previously reported modified electrodes for THP. Modifier/electrode c

CdSe/GCE BBFT-IL-GPEd Au-NPs-CHIT–IL-graphene/GCEe AuNPs/MIP/GCEf Aminotriazole-AuNPs/GCEg WO3/MWCNT/GCE a b c d e f g

LWRa (μM)

LODb (μM)

Sensitivity (μA μM−1)

Ref.

1-40 12-1200 0.025-2.1 0.4-15 0.04-100 0.025–2.6

0.4 9.2 0.001 0.1 0.009 0.008

0.12 0.01 3.08 – 0.09 4.50

[8] [9] [10] [11] [12] This work

Linear working range. Limit of detection. CdSe microparticles/GCE. 1-(4-bromobenzyl)-4-ferrocenyl-1H-[1,2,3]-triazole (1,4-BBFT)- ionic liquid/GPE. Gold nanoparticles–chitosan–ionic liquid-graphene/GCE. Molecular imprinting polymer based on gold nanoparticles/ GCE. Aminotriazole grafted gold nano.

mechanism in Fig. 2. On the other hand, the peak current magnitudes were decreased with increasing the pH of solution (Fig. 6b). At lower pH the protonation of THP is more convenient and thus must be accumulated more effectively on the electrode surface due to the electrostatic interactions [50]. Thus, pH = 1.3 was chosen as the optimum pH for measurement of THP due to the higher peak current.

considered as the most concentration limit of interference that the measured current deviates from the defined range (the mean of measurements in the absence of the interfere ± three times of this measurement standard deviation). As seen, there is no interference species at the studied concentration ranges. Therefore, it can be concluded that the effects of the probable foreign species or excipients present in biological and pharmaceutical samples in determination process of THP are very low.

3.7. Effect of accumulation time and potential The increase in the accumulation time can lead to increase the voltammetric peak current which consequently affects the electrode sensitivity. The influence of accumulation time was examined at a constant accumulation potential (0.2 V) for different accumulation time in the range of 0 to 300 s at the presence of 2 × 10−6 M THP (Fig. 7a). According to the obtained data, the anodic peak current firstly increased, and then attained approximately to a constant level after 210 s. The constant level of the current can be ascribed to the saturation of the electrode surface with the electro-active species. The dependence of the peak current to the accumulation potential was also studied by applying various potentials from −0.3 to 0.6 V after 210 s accumulation time and the obtained results are shown in Fig. 7b. It was concluded that the peak current was enhanced due to the increasing of applied potential up to 0.2 V. Thus, for all following experiments, 210 s and 0.2 V were applied as the optimum accumulation time and potential.

3.10. Analytical application The application ability of the proposed modified GCE was examined by the measurement of THP content in pharmaceutical tablets (Dr Abidi Company, Tehran, Iran). The calibration curve method was applied for the measurement and the results are shown in Table 1. The THP content of tablets was found to be 194 ± 5 mg which was consistent with the declared amount. The selectivity of the proposed procedure makes it efficient for THP analysis in biological samples. Thus, it was applied to the measurement of THP in urine sample as a good real matrix to assess more practical application of the proposed modified electrode. Various quantities of THP were added to the diluted (eightfold) urine sample and the amounts of THP were determined by standard addition procedure and the mean results were obtained. The corresponding standard addition plot is shown in Fig. S2 and the obtained values are summarized in Table 1. The results indicated that the recoveries were quantitative at different THP concentrations indicating the modified GCE can be useful in determination of THP and with good precision and accuracy.

3.8. Calibration curve and analytical parameters To establish a calibration curve for the proposed sensor, the determination of THP using WO3/MWCNT/GCE was performed with adsorptive stripping differential pulse voltammetry under the optimized experimental parameters and the obtained data are shown in Fig. 8. The current was found to be linear in the concentration ranges from 2.5 × 10−8 to 2.6 × 10−6 M (R2 = 0.997) with linear regression equation as Ip(μA) = 4.5062C (×10−6 M) – 0.1175 (Fig. 8). The detection limit (based on the signal-to-noise ratio of 3) for 10 replicates determination of the blank solution was found to be 8.3 × 10−9 M. The low detection limit ensures that the optimized sensor can be employed for sensitive determination of THP content in different media. The relative standard deviation (RSD) for successive measurements of 0.4 and 0.1 μM THP was obtained 2.6% and 3.3% (n = 5), respectively.

3.11. Comparison of developed method with previous electrochemical methods Table 2 shows the analytical performance of the proposed modified electrode and those previously reported methods for the electrochemical determination of THP to in order to make a comparison. The comparative data showed the superiority of the developed method, in most cases, over the earlier reported methods, especially, in terms of the sensitivity, linear working range and limit of detection. These features of the modified electrode are most likely due to the unique the electrochemical characteristics of WO3/MWCNT composite such as large surface area, high absorption capability and excellent conductivity on the GCE surface.

3.9. Interference study

4. Conclusions

The effect of foreign species as potentially interference in the determination process of THP was investigated under the optimal conditions with 2.0 μmol L−1 THP at 0.05 M H2SO4. The results are shown in Table S1. The interferent criterion for the diverse species was

An electrochemical sensor for the fast and selective determination of THP was developed by the modification of a GCE with the composite of tungsten trioxide nanoparticles and multiwall carbon nanotubes. The 6

Microchemical Journal 149 (2019) 104005

S.A. Rezvani and A. Soleymanpour

WO3/MWCNT/GCE characteristics were studied by the various techniques. It was demonstrated that the modified electrode exhibited better electrochemical performance than the bare GCE and MWCNT/ GCE which was related to the larger electroactive area and more conductivity of WO3/MWCNT. The sensor showed high sensitivity, very low detection limit and good selectivity toward THP. THP can be accurately determined up to 2.5 × 10−8 M by the proposed sensor. The sensor permits the measurement of THP in different real samples such as pharmaceutical formulation and urine without any prior separation steps. Furthermore, the sensor is comparable, even superior, to those previous reported electrochemical sensor with respect to detection limit and linear range.

[16]

[17]

[18]

[19]

Acknowledgement [20]

We gratefully acknowledge the support of this work by Damghan University Research Council.

[21]

Appendix A. Supplementary data

[22]

Supplementary data to this article can be found online at https:// doi.org/10.1016/j.microc.2019.104005.

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