The electrochemical behavior of paracetamol (PA) and dopamine (DA) has been investigated by cyclic voltammetry (CV), differential pulse voltammetry (DPV) and square wave voltammetry (SWV) using a selective and sensitive iron oxide (Fe2O3) nanoparticle modified carbon paste electrode (IOCPE).
Journal of Science: Advanced Materials and Devices (2019) 442e450 Contents lists available at ScienceDirect Journal of Science: Advanced Materials and Devices journal homepage: www.elsevier.com/locate/jsamd Original Article Iron oxide (Fe2O3) nanoparticles modified carbon paste electrode as an advanced material for electrochemical investigation of paracetamol and dopamine M.M Vinay, Y Arthoba Nayaka* Department of Chemistry, School of Chemical Science, Kuvempu University, Shankaraghatta, 577451, Karnataka, India a r t i c l e i n f o a b s t r a c t Article history: Received 10 April 2019 Received in revised form 22 July 2019 Accepted 28 July 2019 Available online 12 August 2019 The electrochemical behavior of paracetamol (PA) and dopamine (DA) has been investigated by cyclic voltammetry (CV), differential pulse voltammetry (DPV) and square wave voltammetry (SWV) using a selective and sensitive iron oxide (Fe2O3) nanoparticle modified carbon paste electrode (IOCPE) The PA and DA showed an anodic peak potential at 0.458 V and 0.247 V and a cathodic peak potential at 0.088 V and 0.11 V (vs Ag/AgCl), respectively In the DPV mode, PA and DA gave linear responses over the concentration range of 2e150 mM (R2 ¼ 0.998) and 2e170 mM (R2 ¼ 0.989), respectively The limit of detection (LOD ¼ s/m) for PA and DA were found to be 1.16 and 0.79 mM, respectively IOCPE possesses an excellent electrocatalytic activity towards the determination of PA and DA The proposed method could be successfully validated for the simultaneous and individual determination of PA and DA present in pharmaceutical and real samples © 2019 The Authors Publishing services by Elsevier B.V on behalf of Vietnam National University, Hanoi This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) Keywords: Carbon paste electrode Differential pulse voltammetry Electrochemical impedance spectroscopy Iron oxide nanoparticles Introduction Paracetamol (PA) (N-acetyl-p-aminophenol or acetaminophen) is one of the most widely used analgesic and antipyretic drugs [1] PA releases the pain associated with headache, backache, arthritis and postoperative effect, and it is commonly used for reducing fever [2] PA having a pKa value of 9.5, rapidly gets distributed after oral administration and is easily excreted in urine PA does not exhibit any harmful side effects, but in few cases, it leads to the formation of liver damage and nephrotoxic metabolites [3] An overdose of PA leads to hepatic toxicity, liver and kidney damage and in some cases causes death [4] Dopamine (DA), another most leading catecholamine-based neurotransmitter drug, is monitoring the central nervous system (CNS) by arbitrating the multiple CNS functions such as memory, learning, neuroendocrine secretion, cognition and control of locomotion The difference in the concentration of the DA level may lead to severe causes such as Parkinson's disease, depression, schizophrenia and Huntington's disease, HIV infection, epilepsy and senile dementia [5] So, it is necessary to determine the drugs present in pharmaceutical * Corresponding author Fax: ỵ9108282 256255 E-mail address: drarthoba@yahoo.co.in (Y Arthoba Nayaka) Peer review under responsibility of Vietnam National University, Hanoi samples and human biological fluids (urine and blood) Therefore, the development of simple, rapid, sensitive, and precise analytical procedures for the detection and quantification of these drugs is of great importance [6] Numerous methods are available for the determination of PA and DA such us spectrophotometry [7], TLC [8], HPLC [9,10], LC-MS [11], flow-injection analysis [12], UV-Vis spectrometry [13], electrochemical methods [14], fluorimetry methods [15] and chemiluminescence methods [16] The electrochemical techniques have received a remarkable consideration due to their unique qualities such as a simple pretreatment procedure, good sensitivity, better selectivity, less time-consumption and low cost [17] In recent years, the modification of the electrode surface fascinated significant attention because of its extremely enhanced sensitivities A literature survey reveals that PA and DA undergo electrochemical reactions at different electrodes, such as graphite electrodes (GE) [18], polyurethane modified GE [19], glassy carbon electrodes (GCE) [20], modified GCE [21], screen-printed electrodes [22], carbon paste electrodes (CPE) [23], modified CPE [24], carbon fiber microelectrodes [25], carbon ionic liquid electrodes [26], platinum electrodes [27], gold electrodes [28] and boron doped diamond electrode (BDDE) [29] Currently, metal nanoparticles, nanodiamonds, fullerenes, carbon nanotubes, etc., are being used in biomedical and sensor applications, since nanomaterials possess fundamental features https://doi.org/10.1016/j.jsamd.2019.07.006 2468-2179/© 2019 The Authors Publishing services by Elsevier B.V on behalf of Vietnam National University, Hanoi This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) M.M Vinay, Y Arthoba Nayaka / Journal of Science: Advanced Materials and Devices (2019) 442e450 like smaller size, good optical, magnetic and mechanical properties [30] Metal nanoparticles have much more considerations during the last few decades due to their unique properties as well as to a large surface-to-volume ratio as compared to their bulk counter parts [31] The various electrochemical methods are available for the determination of drugs and these have been reported in the literature The modification of carbon paste electrode with different metal nanoparticles can improve the performance in terms of sensitivity and selectivity and, hence, fastens the rate of electron transfer between the electroactive species and the electrode surface Several metal nanoparticles are reported in literature, such as platinum [32], gold [33], silver [34], copper [35] as well as metal oxide nanoparticles MnO2 [36], NiO [37] CuO [38], and ZnO [39] that were used for the development of electrochemical sensors The Fe2O3 nanoparticles revealed sole features which powerfully differ from those of massiveness phases The electronic, magnetic and optical properties of Fe2O3 nanoparticles have a wide applicability in many industrial processes including extended new electronic and optical devices, information storage, magnetocaloric refrigeration, color imaging, bioprocessing, ferrofluid technology or the manufacture of magnetic recording media [40] The present work reports on the determination of PA and DA simultaneously, using electrochemical techniques such as CV, DPV, SWV and EIS The analytical applications of IOCPE have been tested via the redox reaction of PA and DA present in biological (urine and serum) and pharmaceutical samples The proposed modified electrode IOCPE has got a low limit of detection, good sensitivity, better selectivity and so it could be used for the estimation of PA and DA present in pharmaceutical and real samples Experimental 2.1 Apparatus All the voltammetric experiments were carried out using the Electrochemical Workstation (Model number: CH Instrument 660D, USA) The electrochemical experiments were performed using a conventional three-electrode system The IOCPE, platinum wire and silver/silver chloride were used as working, auxiliary and reference electrode, respectively The Equiptronics EQ-611 pH meter was used for the pH measurements All the electrochemical studies were carried under lab temperature 2.2 Chemicals and reagents The standard drugs Paracetamol (Acetaminophen) (!99%) and Dopamine hydrochloride (!99%) have been procured from Sigma Aldrich (USA and Germany, respectively), di-Potassium hydrogen phosphate anhydrous (!98%), Potassium hydrogen phosphate (!98%) and Potassium chloride purified (!99%) were procured from Merck (Mumbai, India) Silicon oil and Potassium ferricyanide (III) (99%, A.R.) were obtained from Himedia (Mumbai, India) Paracetamol tablets and Dopamine injection tubes have been purchased from the local market (Shivamogga, India) PBS of 0.1 M was prepared (lab temperature at 26 ± C) and the pH was adjusted using NaOH and H3PO4 All the solutions were prepared using doubly distilled water 2.3 Procedure 2.3.1 Preparation of iron oxide nanoparticles (ION's) Iron oxide nanoparticles have been synthesized by a simple precipitation method under laboratory condition using FeCl3.6H2O and liquid ammonia The stoichiometric ratio of FeCl3.6H2O powder 443 has been dissolved in doubly distilled water and stirred well To this constant stirring solution, 14% of NH4OH solution has been added drop-wise (0.2 ml minÀ1) with maintaining the pH-value of 8.0 The obtained brown colored iron oxide was filtered The excess of base was washed with water and the remains were dried in an oven for about 12 h, and finally subjected to calcination at 500 C for h The so obtained Fe2O3 sample has been characterized by scanning electron microscopy (SEM), energy dispersive X-Ray analysis (EDAX) and X-ray diffraction (XRD) techniques [41,42] 2.3.2 Preparation of bare carbon paste electrode (BCPE) and IOCPE The working electrode (IOCPE) was developed by mixing graphite powder, silicon oil and ION's in the ratio 76:20:4 (w/w) and the resultant mixture was thoroughly homogenized using mortar and pestle The obtained paste was tightly packed into a glass tube (60 mm height, mm diameter) without any air gap The electrical contact has been made at one end by inserting a copper wire through the center of the paste packed glass tube without any crack The exposed end of the electrode was mechanically polished and renewed using butter sheet to get a reproducible smooth and shiny working surface This operation has been repeated before start of each experiment The BCPE has been prepared in the same way without the addition of a modifier Result and discussion 3.1 Characterization of the prepared ION's and IOCPE The prepared ION's sample has been characterized by a powder X-ray diffractometer (Cu-Ka, radiation at l ¼ 1.5406 Å) to confirm the physical properties like structure, crystallinity, lattice planes etc Fig 1(a) depicts the reflection planes (220), (311), (400), (422), (511), (440) corresponding to the 2q angles values of 30.26, 35.65, 43.32, 53.77, 57.32 and 62.98, respectively These values were well matches with standard JCPDS file no.: 39e1346 (volume-582.5, lattice-primitive, system-cubic, space group-P4132, cell parameter a ¼ 8.351) The sharp peak with the small FWHM (full width at half maximum) showed that the sample has got a good crystallinity The DebyeeScherrer formula has been used for the calculation of the crystallite size and was found to be 27 nm Fig 1(b) represents the SEM image of synthesized iron oxide nanoparticles, which shows that the prepared nanoparticles were agglomerated The EDAX analysis has shown energy peaks of iron oxide nanoparticles in the range 0.5e6.5 keV corresponding to iron and oxygen atoms of the prepared iron oxide nanoparticles (figure not shown) and has revealed that iron oxide has got a crystalline nature [43] Fig 1(c) represents the SEM (analysis of surface morphology) image of the prepared IOCPE d¼ 0:963l bcosq (1) 3.2 Electrochemical behavior of [Fe(CN)6]3À/4À couple The electrochemical behavior of IOCPE has been monitored through the redox process of [Fe(CN)6]3À/4Àcouple Fig shows the cyclic voltammograms obtained a) in the absence of analyte at IOCPE; b) at BCPE and c) at IOCPE in mM K3[Fe(CN)6] containing 0.1 M KCl solution In the forward scan (positive scan) Fe[(CN)6]3was electrochemically oxidized from Fe[(CN)6]4- (anodic process) and in the reverse scan (negative scan) this Fe[(CN)6]3- has been reduced back to Fe[(CN)6]4- (cathodic process) The obtained voltammogram of [Fe(CN)6]3À/4Àcouple shows a peak to peak separation potential (DEp) of 309 mV and 136 mV, at BCPE and IOCPE, 444 M.M Vinay, Y Arthoba Nayaka / Journal of Science: Advanced Materials and Devices (2019) 442e450 Fig Characterization of the prepared ION's: (a) X-ray diffraction spectrum; (b) SEM image of the iron oxide nanoparticles; (c) SEM image of the prepared IOCPE 1=2 Ip ¼ 2:69 Â 105 A n3=2 D0 C *0 v1=2 (2) where Ip and n refer to the peak current (mA) and scan rate (V sÀ1), A is the active surface area of electrode (cm2), Do and C0* represent the diffusion co-efficient (cm2 sÀ1) and bulk concentration of K3[Fe(CN)6] (mol cmÀ3), respectively The diffusion co-efficient for mM K3[Fe(CN)6] in 0.1 M KCl can be obtained by plotting Ipa vs n1/ (n ¼ 1, Do ¼ 7.6 Â 10À6 cm2 sÀ1) [9] On substituting the above values, the effective surface areas of BCPE and IOCPE were found to be 0.116 cm2 and 0.1786 cm2, respectively 3.3 Effect of modifier (ION's) concentration Fig Cyclic voltammograms of: (a) blank at IOCPE; (b) BCPE; (c) IOCPE in mM K3[Fe(CN)6] containing 0.1 M KCl (at scan rate 100 mV sÀ1) respectively The value of DEp has been decreased at IOCPE compared to BCPE and it clearly indicated the more-reversible charge-transfer process at IOCPE than that of BCPE Also the peak currents for [Fe(CN)6]3À/4À couple have been enhanced at IOCPE compared to BCPE The decrease in DEp value with the increase in peak current suggested that the IOCPE has got an increased surface area compared to BCPE This may be due to the presence of iron oxide nanoparticles that enhance the electron transfer rate The surface area of BCPE and IOCPE have been calculated by the Randles-Sevcik equation using mM K3[Fe(CN)6] in 0.1 M KCl solution at different scan rate [44] The effect of the modifier concentration was studied by cyclic voltammetry using the mM PA in PBS (pH 7.0) and plotting the graph of current vs potential (Fig - supplementary) The 4-wt% of ION's in carbon paste electrode demonstrates a good redox behavior of PA compared to other compositions The resistive electrochemical signal was observed for more than 4-wt% of the modifier This may be an indication that the saturation point of iron oxide nanoparticles has been attained and, hence, this electrode composition has been selected for further electrochemical studies 3.4 Electrochemical characterization of IOCPE Electrochemical impedance spectroscopy (EIS) is an efficient method to analyze the interfacial properties of surface modified electrodes and it provides valuable information regarding the impedance change at the electrode surface EIS uses the frequency sweep of very minute AC voltage modulated over DC bias to extract the equivalent circuit The circuit has been obtained by plotting the M.M Vinay, Y Arthoba Nayaka / Journal of Science: Advanced Materials and Devices (2019) 442e450 real and imaginary part of impedance (Nyquist diagram) [45] The electron charge transfer resistance (Rct) has been measured from the semicircle diameter of the Nyquist plots Fig explains the Nyquist diagram of mM K3[Fe(CN)6] containing 0.1 M KCl at BCPE and IOCPE in the frequency range from 0.1 to 103 kHz An equivalent circuit has been preferred to fit the obtained impedance data and the results showed that the Rct value of BCPE was found to be 181.3 kU (open circuit potential (OCP) ¼ 0.2891 V and error ¼ 0.421) and for IOCPE it was 34.06 kU (OCP ¼ 0.2931 V and error ¼ 0.3857) A decrease in the diameter of the semicircle was observed for IOCPE due to the fast-interfacial electron transfer process and low resistance value A ow resistance value of IOCPE indicates the presence of ION's in carbon paste which accelerates the electron transfer process and leads to good electrical conductivity The smaller semicircle diameter was viewed due to synergistic effect of ION's The synergistic consequence could significantly develop the interfacial electron transfer capability and redox reaction of the probe on the electrode surface This indicated that the presence of mediator ION's on CPE played a significant role in increasing the charge transfer capability [46e48] 3.5 Voltammetric behaviors of PA and DA at BCPE and IOCPE The BCPE and IOCPE electrodes were used for the investigation of the PA signal by cyclic voltammetry The curve a in Fig depicts the cyclic voltammogram (CV) of a blank solution at IOCPE and curve b and c shows the cyclic voltammograms (CVs') in presence of mM PA in PBS (pH 7.0) at BCPE and IOCPE, respectively at a scan rate 100 mV sÀ1 (Fig 5) At IOCPE, PA exhibits the quasi-reversible redox behavior with an anodic (Epa) and cathodic peak potential (Epc) of 45 and 8.8 mV, respectively The significant enhancement of the anodic (Ipa) and cathodic peak currents (Ipc) provides a clear evidence for the catalytic effect of IOCPE towards the redox behavior of PA [44,49] After 120 days, the same procedure has been performed for the determination of PA and DA using the same IOCPE The curves e and f show CVs' for blank solution and mM DA at BCPE, respectively, and curve d and g represents the redox behavior of mM PA and mM DA at IOCPE, respectively in PBS (pH 7.0) at scan rate 100 mV sÀ1 (Fig 5) The results have shown that even after long storage, the working electrode IOCPE has retained its good sensitivity and stability for the determination of PA and DA 3.6 Effect of scan rate and pH The influence of the scan rate on the peak currents (Ip) of PA at IOCPE was investigated by cyclic voltammetry Fig 6(a) shows the Fig Nyquist plots of mM K3[Fe(CN)6] containing 0.1 M KCl at: (a) BCPE; (b) IOCPE (frequency range from 0.1 to 103 kHz, inset: Randle's equivalent circuit) 445 Fig CV's of: (a) and (e) buffer at IOCPE; mM PA at (b) BCPE; (c) and (d) IOCPE; and mM DA at (f) BCPE; (g) IOCPE at scan rate of 100 mV sÀ1 ((d), (e), (f) and (g) obtained at IOCPE after 120 days) voltammetric response of mM PA at IOCPE at different scan rates of 50e350 mV sÀ1 The redox peak current increases linearly with increasing scan rate and the reduction peak shifts towards a more negative potential whereas the oxidation peak shifts towards a more positive potential which indicates to the diffusion-controlled kinetics of the electron transfer reaction at the electrode surface Linear regression equations were obtained from the graph Ipa and Ipc vs n1/2 (square root of scan rate) as follows; Ipa ẳ 11.11 106 ỵ 6.892 n1/2, (R2 ẳ 0.999; N ¼ 12); Ipc ¼ 22.85 Â 10À6 - 5.516 n1/ , (R2 ¼ 0.9977; N ¼ 12) for the anodic and cathodic process, respectively, which indicates that the reaction of PA at IOCPE is diffusion controlled [49] The linear relationship between log Ipa vs log n can be obtained as follows; log Ipa ẳ 5.383 ỵ 0.572 log n(mV sÀ1), (R2 ¼ 0.9993; N ¼ 12) The slope value 0.57 is very close to the theoretical value of 0.5 and confirms that the reaction at the electrode surface is diffusion controlled [50,51] For comparison, the scan rate from 50 to 250 mV sÀ1 was performed for PA and DA individually using a long-stored working electrode (IOCPE) The redox peak currents of both PA and DA were obtained and found to be increased linearly with increase in scan rate (Fig 6(b) and (c)) The linear correlation equations have been given by: Ipa ẳ 28.07 106 ỵ (4.87 Â 10À6) v1/2, (R2 ¼ 0.9965; N ¼ 9); Ipc ẳ 27.85 106 ỵ 3.503 106 v1/2, (R2 ¼ 0.9993; N ¼ 9) for PA and Ipa ¼ 5.8 106 ỵ (3.21 106) v1/2, (R2 ẳ 0.9937; N ẳ 9); Ipc ẳ 14.49 106 ỵ 2.56 Â 10À6 v1/2, (R2 ¼ 0.9984; N ¼ 9) for DA The plots of log Ipa vs log n for PA and DA as follows; log Ipa ¼ À4.744 þ 0.417 log n(mV sÀ1), (R2 ¼ 0.9917; N ¼ 9) and log Ipa ẳ 5.237 ỵ 0.41 log n(mV sÀ1), (R2 ¼ 0.9903; N ¼ 9), respectively The slope values for PA and DA have been found to be 0.417 and 0.41, respectively and these confirmed that the redox processes of PA and DA at IOCPE were diffusion controlled [42,50,51] The CVs' were performed in the scan rate from 50 to 225 mV sÀ1 for determination of the number of electrons transferred and the electron transfer coefficients in PA and DA The linear regression equations (Epa and Epc vs log n) for PA and DA are as follows: Epa (PA) ẳ 0.3438 ỵ 0.08 log n (R2 ẳ 0.9948); Epc (PA) ¼ 0.2512e0.09 log v (R2 ¼ 0.9927) and Epa (DA) ẳ 0.254 ỵ 0.061 log v (R2 ẳ 0.9969); Epc (DA) ¼ 0.2431e0.078 log v (R2 ¼ 0.9927) According to Laviron's equation, the slopes of line obtained from the above linear regression equations have been found to be 2.303RT/(1-a)nF and À2.303RT/anF, where R is the gas constant (8.314 J KÀ1 molÀ1), T is the temperature (298 K), F is Faraday's constant (96,485 C), n and a are the electron-transfer number and electron-transfer coefficient, respectively The electron-transfer number and electron- 446 M.M Vinay, Y Arthoba Nayaka / Journal of Science: Advanced Materials and Devices (2019) 442e450 Fig Effect of pH (from 4.0 to 9.0) on SWV's of 20 mM PA and 50 mM DA: (frequency 15 Hz; amplitude 25 mV; inset: linearity plot of pH vs potential) Fig (a) CV's of mM PA at different scan rate from 50 to 350 mV sÀ1 in 0.1 M PBS at pH 7.0; (inset: linearity plot of current vs scan rate and log current vs log scan rate) (b) and (c) CV's of individual scan rates of mM PA and mM DA, respectively at different scan rate from 50 to 250 mV sÀ1 (a to i) in 0.1 M PBS (pH 7.0) at long stored IOCPE (inset: linearity plot of PA and DA from log peak current vs log scan rate) transfer coefficients for PA and DA have been found to be 1.7 (z2), 1.9 (z2) and 0.43, 0.51 respectively The square wave voltammetric method (frequency 15 Hz; amplitude 25 mV) has been employed to investigate the effect of pH on the electrochemical behavior of PA (20 mM) and DA (50 mM) in 0.1 M PBS Fig shows the variation of peak currents at different pH and the inset plot shows the variations of the peak potentials with pH The shift in the peak potentials towards the negative side with increase in pH indicates the involvement of protons in the reaction The increase in the peak current with the increase in pH (from 4.0 to 6.0) in case of PA is attributed to the formation of pbenzoquinone The maximum peak current obtained at pH 7.0 is due to the formation of N-acetyl-p-quinone-imine which exists in unprotonated stable form [52,53] At higher pH values (above 8.0) the peak current is found to decrease which is due to the dimerization of N-acetyl-p-benzoquinone-imine [54] The above results clearly indicated that at pH 7.0 a good electrostatic interaction exists between unprotonated PA and IOCPE which, in turn, is responsible for the fast electron transfer reaction Hence PBS of pH 7.0 has been selected as an appropriate standard electrolytic medium for further studies [55] The square wave peak potential for PA has a linear relationship with pH (from 4.0 to 8.0) and the corresponding regression equation has been given by the following equation: Ep (V) ¼ 0.739e0.050 pH (R2 ¼ 0.9993) Further from pH 4.0 to 6.0, the square wave peak potential of DA is found to be shifted towards the negative side and at pH 7.0 a rapid increase in the peak current was observed Above pH 8.0, the peak potential again shifted towards the negative side with a decrease in peak current that may be due to self-polymerization of DA into polydopamine in an alkaline medium [56] The corresponding linear regression equation for DA is as follows: Ep (V) ¼ 0.562e0.0558 pH (R2 ¼ 0.9993) The slope value for PA and DA were found to be 50 and 55 mV pHÀ1 respectively These values are nearly equal to the theoretical value of 59 mV pHÀ1 which is in good agreement with the Nernst equation These results indicated that the electrochemical redox process of PA and DA at IOCPE involves two protons and two electrons transfer reactions [52,57] The probable redox reaction mechanisms of PA and DA are shown in (Scheme Supplementary) 3.7 Effect of concentration The DPV method has been employed for the electrochemical detection of PA at IOCPE Fig shows the differential pulse voltammograms (DPVs') for different concentration of PA (1 mMe14 mM) in 0.1 M PBS at pH 7.0 The oxidation peak current is directly proportional to the concentration of PA and increases linearly with the increase in concentration The linear regression equation for PA is as follows: Ip(mA) ¼ À7.65 Â 10À7 2.19 Â 10À2 C(mM) and the correlation coefficient R2 ¼ 0.9994 The limit of detection (LOD) can be detected by using the formula LOD ¼ s/m where s indicates the standard deviation of the first five runs and where m indicates the slope obtained from a linear graph (concentration vs current) and where LOD has been found to be equal to 0.904 The IOCPE has shown an enhanced performance for the electrochemical determination of PA After 120 days, the above experimental procedure has been repeated for the analysis of PA and DA using the same IOCPE Fig 9(a) shows DPVs' of PA keeping the concentration of DA at a constant value and Fig 9(b) represents DPVs' of DA keeping the concentration of PA at a constant value Fig 9(c) shows DPVs' for the simultaneous estimation M.M Vinay, Y Arthoba Nayaka / Journal of Science: Advanced Materials and Devices (2019) 442e450 447 Fig DPV plots at IOCPE of different concentration from to 14 mM (a to l) obtained at IOCPE in 0.1 M PBS at pH 7.0; (inset: linearity graph of current vs concentration) of PA and DA The concentration of PA has been varied from to 150 mM keeping the DA concentration at 15 mM where the regression equation is given by: Ipa (PA) ¼ 7.74 107 ỵ 1.7 102 C(mM) with correlation coefcient R2 ¼ 0.9982 Similarly, the DA concentration has been varied from to 170 mM keeping PA at 14 mM where the corresponding regression equation is as follows: Ipa (DA) ẳ 1.45 106 ỵ 2.49 102 C(mM) with correlation coefficient R2 ¼ 0.989 From the regression equations, the LOD values have been calculated as 1.16 and 0.79 mM (S/N¼3) for PA and DA, respectively It was observed that the change in concentration of one species does not alter the peak potential and current of the other species Further, the concentrations of both PA and DA have been varied from to 170 mM and they exhibited well- separated peaks with the following regression equations: 9.35 107 ỵ 1.367 Â 10À2 C(mM) (R2 ¼ 0.9924) for PA and 1.44 106 ỵ 1.81 102 C(mM) (R2 ẳ 0.9786) for DA From the above equations, the LOD values were found to be 1.44 and 1.09 mM and these values are in good agreement with the individual determination of PA and DA The above results show that the modified electrode IOCPE exhibited good and acceptable LOD and LR values compared to other modified electrodes reported in literature (Table - Supplementary) 3.8 Interference, stability and repeatability In order to estimate the optionality of IOCPE, the effect of interference has been studied via the DPV technique by adding a known concentration of important interfering organic compounds like glucose, vitamin-c, cysteine, methionine, tyrosine and inorganic species Naỵ, Kỵ, Ca2ỵ, Mg2ỵ, Cl, SO2À into the analytical solution containing 20 mM PA and 20 mM DA The obtained results showed that interfering compounds have no effect on the peak current and peak potential of PA and DA The percent recovery of both analyte PA and DA in presence of interfering substance has been calculated and the obtained RSD value is 1.2% In sensor applications, long-lasting stability was the most important criterion So, the stability of the prepared modified Fig DPV's plots at IOCPE after 120 days; (a) variation of PA under fixed concentration of 15 mM DA (from a to m; 2, 4, 6, 10, 20, 30, 40, 50, 60, 80, 110, 150 mM respectively); (b) variation of DA under fixed concentration of 14 mM PA (from a to j; 2, 4, 6, 10, 30, 50, 50, 80, 120, 170 mM respectively); (c) variation of both PA and DA (from a to m; 1, 2, 4, 7, 11, 16, 22 30, 50, 80, 120, 170 mM respectively) in 0.1 M PBS at pH 7.0: (all inset: linearity graph of current vs concentration) 448 M.M Vinay, Y Arthoba Nayaka / Journal of Science: Advanced Materials and Devices (2019) 442e450 Table Analytical application of PA and DA in pharmaceutical sample (standard addition method, n ¼ 3) Analyte Tablet-1 (Dolo-650) 2 Tablet-2 (Oromol-650) Injection (Dopamine Hydrochloride) Table Analytical application of PA alone in real sample (standard addition method, n ¼ 3) Analyte Serum Spiked (mM) Found (mM) % Recovery 12 4.160 ± 0.5 7.830 ± 0.5 11.66 ± 0.5 96.15 102.17 102.91 electrode has been evaluated by CV in the presence of mM PA Even after being stored at the lab temperature (25 ± C) for 120 days, the peak potential of PA remained almost constant in the applied potential range À0.2e0.8 V but the current response was slight decreased of its preliminary value Further repeatability of IOCPE towards the estimation of PA and DA has been analyzed by preparing four different electrodes under the same experimental condition with the RSD value found to be equal to 2.4% These results have shown that the prepared electrode has good stability, reproducibility and could be used for determination of PA and DA 3.9 Real sample analysis 3.9.1 Determination of PA and DA in pharmaceutical samples The analytical applicability of the prepared IOCPE has been tested by determining PA present in tablets Dolo (Dolo-650, IP 650 mg) and Oromol (Oromol-650, IP 650 mg), and DA present in an injected sample (Dopamine hydrochloride, U S P 200 mg) The Dolo and Oromol tablets were weighed separately and powdered using a mortar A known amount of Dolo (0.5 g) and Oromol (0.5 g) tablets was dissolved separately in 100 ml of PBS of pH 7.0 and sonicated for 15 and filtered Similarly, the Dopamine hydrochloride injection sample (5 ml injection containing 200 mg Dopamine hydrochloride) was also dissolved in 100 ml of 0.1 M PBS The concentration of the so prepared tablets and of the injection sample solutions has been studied using the DPV technique within the adjusted calibration range as shown in Fig 9(C) Also, the concentration of PA present in a synthetic serum sample has been determined The obtained DPV results indicate the applicability of IOCPE for the estimation of PA and DA present in pharmaceutical samples and PA in serum samples (Tables and 3) Conclusion The prepared ION's and IOCPE have been characterized by SEM, EDAX, XRD techniques The surface area and impedance of IOCPE have been studied by CV and EIS The ION's present in the carbon paste enhances the good electron transfer ability, sensitivity and selectivity towards the determination of redox behavior of PA In the DPV mode, PA gave the linear response over the concentration range 3.0e14 mM with a LOD value of 0.904 mM Similarly, the effects of scan rate, pH, concentration, interference, stability and reproducibility of the IOCPE (long stored electrode for 120 days) have been analyzed for PA and DA simultaneously In the DPV mode, PA and DA gave linear responses over the concentration range 2e150 mM (R2 ¼ 0.998) and 2e170 mM (R2 ¼ 0.989), Spiked (mM) Found (mM) 30 40 25 50 30 40 29.33 40.33 25.16 49.50 29.66 40.66 ± ± ± ± ± ± 1.0 1.0 0.5 0.5 1.0 1.0 % Recovery 102.28 99.18 99.36 101.01 101.14 98.37 respectively The LOD values of PA and DA were found to be 1.16 and 0.79 mM, respectively The results have shown that IOCPE possesses the good stability, better sensitivity, selectivity, reproducibility, wide linear concentration range and low limit of detection towards the determination of PA and DA So, the proposed method can be successfully validated for the individual and simultaneous determination of PA and DA present in pharmaceutical and real samples Acknowledgements The authors are grateful to acknowledge the UGC-BSR (University Grant Commission-Basic Scientific Research; UGC letter No F.25-1/2013-14 (BSR)/7-229/2009/dated: 30-07-2014), SERB (DST), New Delhi, India for providing financial support and instrument facility Appendix A Supplementary data Supplementary data to this article can be found online at https://doi.org/10.1016/j.jsamd.2019.07.006 References [1] A.P.P Eisele, D.N Clausen, C.R.T Tarley, L.H.D Antonia, E.R Sartori, Simultaneous square-wave voltammetric determination of paracetamol, caffeine and orphenadrine in pharmaceutical formulations using a cathodically pretreated boron doped diamond electrode, Electroanalysis 25 (2013) 1734e1741 https://doi.org/10.1002/elan.201300137 [2] R.T Kachoosangi, G.G Wildgoose, R.G Compton, Sensitive adsorptive stripping voltammetric determination of paracetamol at multiwalled carbon nanotube modified basal plane pyrolytic graphite electrode, Anal Chim Acta 618 (2008) 54e60 https://doi.org/10.1016/j.aca.2008.04.053 [3] R.N Goyal, S.P Singh, Voltammetric determination of paracetamol at C-60modified glassy carbon electrode, Electrochim Acta 51 (2006) 3008e3012 https://doi.org/10.1016/j.electacta.2005.08.036 [4] A.R Khaskhelia, J Fischerb, J Barekb, V Vyskocil, Sirajuddina, M.I Bhangera, Differential pulse voltammetric determination of paracetamol in tablet and urine samples at a micro-crystalline natural graphite-polystyrene composite film modified electrode, Electrochim Acta 101 (2013) 238e242, https:// doi.org/10.1016/j.electacta.2012.09.102 [5] A Ejaz, Y Joo, S Jeon, Fabrication of 1,4-bis (aminomethyl) benzene and cobalt hydroxide at graphene oxide for selective detection of dopamine in the presence of ascorbic acid and serotonin, Sens Actuators B Chem 240 (2017) 297e307, https://doi.org/10.1016/j.snb.2016.08.171 [6] A.M Santos, F.C Vicentini, P.B Deroco, R.C.R Filho, O.F Filho, Square-Wave Voltammetric determination of paracetamol and codeine in pharmaceutical and human body fluid samples using a cathodically pretreated boron-doped diamond electrode, J Braz Chem Soc 26 (2015) 2159e2168 https://doi org/10.5935/0103-5053.20150203 [7] U.G Gonullu, N Erk, Rapid and accurate determination of acetaminophen and phenprobamate in binary mixtures by derivative-differential UV spectrophotometry and ratio-spectra derivative spectrophotometry, Anal Lett 32 (1999) 2625e2639 https://doi.org/10.1080/00032719908542993 [8] N Erk, Application of derivative-differential UV spectrophotometry and ratio derivative spectrophotometric determination of mephenoxalone and acetaminophen in combined tablet preparation, J Pharm Biomed Anal 21 (1999) 429e437 https://doi.org/10.1016/S0731-7085(99)00157-0 [9] I Baranowska, B Kowalski, The development of SPE procedures and an UHPLC method for the simultaneous determination of ten drugs in water samples, Water, Air, Soil Pollut 211 (2010) 417e425 https://doi.org/10.1007/s11270009-0310-7 [10] C Ji, W Li, X dan Ren, A.F.E Kattan, R Kozak, S Fountain, C Lepsy, Diethylation labeling combined with UPLC/MS/MS for simultaneous determination M.M Vinay, Y Arthoba Nayaka / Journal of Science: Advanced Materials and Devices (2019) 442e450 [11] [12] [13] [14] [15] [16] [17] [18] [19] [20] [21] [22] [23] [24] [25] [26] [27] [28] [29] [30] [31] of a panel of monoamine neurotransmitters in rat prefrontal cortex microdialysates, Anal Chem 80 (2008) 9195e9203 https://doi.org/10.1021/ ac801339z W Lohmann, U Karst, Simulation of the detoxification of paracetamol using on-line electrochemistry/liquid chromatography/mass spectrometry, Anal Bioanal Chem 386 (2006) 1701e1708, https://doi.org/10.1007/s00216-0060801-y A.R Medina, M.L Fernandez de cordova, M.J.A Canada, M.I.P Reguera, M Diaz, A flow-through solid phase UV spectrophotometric biparameter sensor for the sequential determination of ascorbic acid and paracetamol, Anal Chim Acta 404 (2000) 131e139 https://doi.org/10.1016/S00032670(99)00693-5 Y.Z Fang, D.J Long, J.N Ye, Study of acetaminophen by parallel incident spectroelectrochemistry, Anal Chim Acta 342 (1997) 13e21 https://doi.org/ 10.1016/S0003-2670(96)00619-8 A.M Galvez, J.V.G Mateo, J.M Calataynd, Study of various indicating redox systems on the indirect flow-injection biamperometric determination of pharmaceuticals, Anal Chim Acta 396 (1999) 161e170 https://doi.org/10 1016/S0003-2670(99)00440-7 G.M Hendy, C.B Breslin, A spectrophotometric and NMR study on the formation of an inclusion complex between dopamine and a sulfonated cyclodextrin host, J Electroanal Chem 661 (2011) 179e185 https://doi.org/10 1016/j.jelechem.2011.07.041 S Saha, P Sarkar, A.P.F Turner, Interference-free electrochemical detection of nanomolar dopamine using doped polypyrrole and silver nanoparticles, Electroanalysis 26 (2014) 2197e2206, https://doi.org/10.1002/ elan.201400332 J Li, J Liu, G Tan, J Jiang, S Peng, M Deng, D Qian, Y Feng, Y Liu, Highsensitivity paracetamol sensor based on Pd/graphene oxide nanocomposite as an enhanced electrochemical sensing platform, Biosens Bioelectron 54 (2014) 468e475, https://doi.org/10.1016/j.bios.2013.11.001 I Baranowska, P Markowski, A Gerle, J Baranowski, Determination of selected drugs in human urine by differential pulse voltammetry technique, Bioelectrochemistry 73 (2008) 5e10, https://doi.org/10.1016/j.bioelechem.2 008.04.022 P Cervini, E.T.G Cavalheiro, Determination of paracetamol at a graphite polyurethane composite electrode as an amperometric flow detector, J Braz Chem Soc 19 (2008) 836e841 https://doi.org/10.1590/S0103-50532008000500005 Q Chu, L Jiang, X Tian, J Ye, Rapid determination of acetaminophen and paminophenol in pharmaceutical formulations using miniaturized capillary electrophoresis with amperometric detection, Anal Chim Acta 606 (2008) 246e251 https://doi.org/10.1016/j.aca.2007.11.015 S.F Wang, F Xie, R.F Hu, Carbon-coated nickel magnetic nanoparticles modified electrodes as a sensor for determination of acetaminophen, Sens Actuators, B 123 (2007) 495e500 https://doi.org/10.1016/j.snb.2006.09.031 N Karikalana, R Karthika, S.M Chena, M Velmurugana, C Karuppiah, Electrochemical properties of the acetaminophen on the screen printed carbon electrode towards the high performance practical sensor applications, J Colloid Interface Sci 483 (2016) 109e117, https://doi.org/10.1016/ j.jcis.2016.08.028 P Norouzi, F Dousty, M.R Ganjali, P Daneshgar, Dysprosium nanowire modified carbon paste electrode for the simultaneous determination of naproxen and paracetamol: application in pharmaceutical formulation and biological fluid, Int J Electrochem Sci (2009) 1373e1386 M.M Ardakani, H Beitollahi, B Ganjipour, H Naeimi, M Nejati, Electrochemical and catalytic investigations of dopamine and uric acid by modified carbon nanotube paste electrode, Bioelectrochemistry 75 (2009) 1e8 https:// doi.org/10.1016/j.bioelechem.2008.11.006 A.G Caballero, M.A Goicolea, R.J Barrio, Paracetamol voltammetric microsensors based on electrocopolymerized-molecularly imprinted film modified carbon fiber microelectrodes, Analyst 130 (2005) 1012e1018, https://doi.org/ 10.1039/b502827b A Safavi, N Maleki, O Moradlou, A selective and sensitive method for simultaneous determination of traces of paracetamol and p-aminophenol in pharmaceuticals using carbon ionic liquid electrode, Electroanalysis 20 (2008) 2158e2162 https://doi.org/10.1002/elan.200804292 N.F Atta, M.F.E Kady, Poly (3-methylthiophene)/palladium sub-micro modified sensor electrode Part II: voltammetric and EIS studies and analysis of catecholamine neurotransmitters, ascorbic acid and acetaminophen, Talanta 79 (2009) 639e647, https://doi.org/10.1016/j.talanta.2009.04.040 R.N Goyal, V.K Gupta, M Oyama, N Bachheti, Differential pulse voltammetric determination of paracetamol at nanogold modified indium tin oxide electrode, Electrochem Commun (2005) 803e807 B.C Lourencao, R.A Medeiros, R.C Rocha, L.H Mazo, O Fatibello, Simultaneousvoltammetric determination of paracetamol and caffeine in pharmaceutical formulations using a boron-doped diamond electrode, Talanta 78 (2009) 748e752 https://doi.org/10.1016/j.talanta.2008.12.040 V Biju, Chemical modifications and bioconjugate reactions of nanomaterials for sensing, imaging, drug delivery and therapy, Chem Soc Rev 43 (2014) 737e962, https://doi.org/10.1039/C3CS60273G J.M Campelo, D Luna, R Luque, J.M Marinas, A.R Antonio, Sustainable preparation of supported metal nanoparticles and their applications in [32] [33] [34] [35] [36] [37] [38] [39] [40] [41] [42] [43] [44] [45] [46] [47] [48] [49] [50] [51] [52] [53] 449 catalysis, Chem Sus Chem (2009) 18e45 https://doi.org/10.1002/cssc 200800227 D Rathod, C Dickinson, D Egan, E Dempsey, Platinum nanoparticle decoration of carbon materials with applications in non-enzymatic glucose sensing, Sens Actuators B Chem 143 (2010) 547e554 https://doi.org/10.1016/j.snb 2009.09.064 E.R Sartori, F.C Vicentini, O.F Filho, Indirect determination of sulfite using a polyphenol oxidase biosensor based on a glassy carbon electrode modified with multi-walled carbon nanotubes and gold nanoparticles within a poly (allylamine hydrochloride) film, Talanta 87 (2011) 235e242 https://doi.org/ 10.1016/j.talanta.2011.10.003 K Tschulik, C.B McAuley, H.S Toh, E.J.E Stuart, R.G Compton, Electrochemical studies of silver nanoparticles: a guide for experimentalists and a perspective, Phys Chem Chem Phys 16 (2014) 616e623, https://doi.org/10.1039/ C3CP54221A R.C Carvalho, A Mandil, K.P Prathish, A Amine, C.M.A Brett, Carbon nanotube, carbon black and copper nanoparticle modified screen printed electrodes for amino acid determination, Electroanalysis 25 (2013) 903e913 https://doi.org/10.1002/elan.201200499 R Liu, J Duay, S.B Lee, Redox Exchange induced MnO2 nanoparticle enrichment in poly (3,4-ethylenedioxythiophene) nanowires for electrochemical energy storage, ACS Nano (2010) 4299e4307 https://doi.org/10.1021/nn1010182 M Roushani, Z Abdi, A Daneshfar, A Salimi, Hydrogen peroxide sensor based on riboflavin immobilized at the nickel oxide nanoparticle-modified glassy carbon electrode, J Appl Electrochem 43 (2013) 1175e1183 https://doi.org/ 10.1007/s10800-013-0603-9 D.W Kim, K.Y Rhee, S.J Park, Synthesis of activated carbon nanotube/copper oxide composites and their electrochemical performance, J Alloy Comp 530 (2012) 6e10 https://doi.org/10.1016/j.jallcom.2012.02.157 X.Y Kong, Y Ding, R Yang, Z.L Wang, Single-crystal nanorings formed by epitaxial self-coiling of polar nanobelts, Science 303 (2004) 1348e1351, https://doi.org/10.1126/science.1092356 C.C Desmond, R.H Gilbert, Industrial applications of the mossbauer effect, Hyperfine Interact 139/140 (2002) 597e606, https://doi.org/10.1007/978-94010-0299-8 S Sankadiya, N Oswal, P Jain, N Gupta, Synthesis and characterization of Fe2O3 nanoparticles by simple precipitation method, Am Inst Phy 1724 (2016) 1e4 https://doi.org/10.1063/1.4945184 C Hao, Y Shen, Z Wang, X Wang, F Feng, C Ge, Y Zhao, K Wang, Preparation and characterization of Fe2O3 nanoparticles by solid-phase method and its hydrogen peroxide sensing properties, ACS Sustain Chem Eng (2016) 1069e1077 https://doi.org/10.1021/acssuschemeng.5b01150 M Vijayakumar, K Priya, F.T Nancy, A Noorlidah, A.B.A Ahmed, Biosynthesis, characterisation and anti-bacterial effect of plant-mediated silver nanoparticles using artemisia nilagirica, Ind Crops Prod 41 (2013) 235e240 https://doi.org/10.1016/j.indcrop.2012.04.017 B.K Chethana, S Basavanna, Y.A Naik, Voltammetric determination of diclofenac sodium using tyrosine-modified carbon paste electrode, Ind Eng Chem Res 51 (2012) 10287e10295 https://doi.org/10.1021/ie202921e Ullmann's encyclopedia of industrial Chemistry: sixth, completely revised edition Volumes 1À40 edited by wiley-VCH, J Am Chem Soc 125 (35) (2003), https://doi.org/10.1021/ja0335566, 10768-10768 H.C.B Kalachar, S Basavanna, R Viswanatha, Y.A Naik, D.A Raj, P.N Sudha, Electrochemical determination of L-Dopa in mucuna pruriens seeds, leaves and commercial siddha product using gold modified pencil graphite electrode, Electroanalysis 23 (2011) 1107e1115 https://doi.org/10.1002/elan.201000558 W Feng, P He, S Ding, G Zhang, M He, F Dong, J Wen, L Dua, M Liu, Oxygen-doped activated carbons derived from three kinds of biomass: preparation, characterization and performance as electrode materials for supercapacitors, RSC Adv (2016) 5949e5956, https://doi.org/10.1039/ C5RA24613J M Mahanthappaa, S Yellappaa, N Kottamb, C.S.R Vusa, Sensitive determination of caffeine by copper sulphide nanoparticles modified carbon paste electrode, Sens Actuators A Phys 248 (2016) 104e113 https://doi.org/10 1016/j.sna.2016.07.013 X Kang, J Wang, H Wu, J Liu, I.A Aksay, Y Lin, A graphene-based electrochemical sensor for sensitive detection of paracetamol, Talanta 81 (2010) 754e759 https://doi.org/10.1016/j.talanta.2010.01.009 M Zidan, T.W Tee, A.H Abdullah, Z Zainal, G.J Kheng, Electrochemical oxidation of paracetamol mediated by nanoparticles bismuth oxide modified glassy carbon electrode, Int J Electrochem Sci (2011) 279e288 J Fuller, R.T Carlin, R.A Osteryoung, The room Temperature ionic liquid 1ethyl-3-methylimidazolium tetrafluoroborate: electrochemical couples and physical properties, J Electrochem Soc 144 (1997) 3881e3886, https:// doi.org/10.1149/1.1838106 W Si, W Lei, Z Han, Y Zhang, Q Hao, M Xi, Electrochemical sensing of acetaminophen based on poly (3,4-ethylenedioxythiophene)/graphene oxide composites, Sens Actuators B Chem 193 (2014) 823e829 https://doi.org/10 1016/j.snb.2013.12.052 T.G Gete, M.M Kassaw, Cyclic voltammetric study of paracetamol at Nickel hexacyanoferrate modified carbon paste electrode, J Nat Sci Res (2016) 28e34 450 M.M Vinay, Y Arthoba Nayaka / Journal of Science: Advanced Materials and Devices (2019) 442e450 [54] D Nematollahi, H.S Jam, M Alimoradi, S Niroomand, Electrochemical oxidation of acetaminophen in aqueous solutions: kinetic evaluation of hydrolysis, hydroxylation and dimerization process, Electrochem Acta 54 (2009) 7407e7415 https://doi.org/10.1016/j.electacta.2009.07.077 [55] B.K Chethana, Y.A Naik, Electrochemical oxidation and determination of ascorbic acid present in natural fruit juices using a methionine modified carbon paste electrode, Anal Methods (2012) 3754e3759, https://doi.org/ 10.1039/C2AY25528F [56] I Kaminska, M.R Das, Y Coffinier, J.N Jonsson, J Sobczak, P Woisel, J Lyskawa, M Opallo, R Boukherroub, S Szunerits, Reduction and functionalization of graphene oxide sheets using biomimetic dopamine derivatives in one step, ACS Appl Mater Interfaces (2012) 1016e1020 https://doi.org/10.1021/am201664n [57] T.L Lu, Y.C Tsai, Sensitive electrochemical determination of acetaminophen in pharmaceutical formulations at multiwalled carbon nanotube-aluminacoated silica nanocomposite modified electrode, Sens Actuators B Chem 153 (2011) 439e444 https://doi.org/10.1016/j.snb.2010.11.013 ... determination of drugs and these have been reported in the literature The modification of carbon paste electrode with different metal nanoparticles can improve the performance in terms of sensitivity and. .. to iron and oxygen atoms of the prepared iron oxide nanoparticles (figure not shown) and has revealed that iron oxide has got a crystalline nature [43] Fig 1(c) represents the SEM (analysis of. .. Dousty, M.R Ganjali, P Daneshgar, Dysprosium nanowire modified carbon paste electrode for the simultaneous determination of naproxen and paracetamol: application in pharmaceutical formulation and biological