MWCNTs nanocomposite for enhanced electrochemical determination of epinephrine and tramadol simultaneously

Journal Pre-proof Designing and characterization of a novel sensing platform based on Pt doped NiO/MWCNTs nanocomposite for enhanced electrochemical determination of epinephrine and tramadol simultaneously

Aliyeh Dehdashti, Ali Babaei PII:

S1572-6657(20)30132-6

DOI:

https://doi.org/10.1016/j.jelechem.2020.113949

Reference:

JEAC 113949

To appear in:

Journal of Electroanalytical Chemistry

Received date:

18 September 2019

Revised date:

9 February 2020

Accepted date:

12 February 2020

Please cite this article as: A. Dehdashti and A. Babaei, Designing and characterization of a novel sensing platform based on Pt doped NiO/MWCNTs nanocomposite for enhanced electrochemical determination of epinephrine and tramadol simultaneously, Journal of Electroanalytical Chemistry(2020), https://doi.org/10.1016/j.jelechem.2020.113949

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© 2020 Published by Elsevier.

Journal Pre-proof Designing and characterization of a novel sensing platform based on Pt doped NiO/MWCNTs nanocomposite for enhanced electrochemical determination of epinephrine and tramadol simultaneously

Aliyeh Dehdashtia, Ali Babaeia,b,1 a

Institute of Nanosciences & Nanotechnology, Arak University, Arak, I.R. IRAN

Jo

ur

na

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re

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ro

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b

Department of Chemistry, Faculty of Science, Arak University, Arak, I.R. IRAN

Abstract 1

Corresponding author. Tel.: +98 863 4173415; Fax: +98 863 4173406. E‒mail address: ali‒[email protected]

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Journal Pre-proof In the present study, we have designed a novel sensing platform based on Pt doped NiO nanoparticles and multi-walled carbon nanotubes (MWCNTs) modified glassy carbon electrode (Pt-NiO/MWCNTs/GCE) to determine epinephrine (EP) and tramadol (TR) simultaneously. To synthesize Pt doped NiO nanoparticles, a simple sol-gel procedure was applied. The structures of the synthesized Pt doped NiO nanoparticles and Pt doped NiO/MWCNTs nanocomposite were characterized using field emission scanning electron microscopy (FESEM), X-ray diffraction

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(XRD) and energy dispersive X-ray spectroscopy (EDX) techniques. According to

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electrochemical studies, the fabricated sensor could accelerate electron transfer reactions of EP

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and TR and boost their oxidation signal. Under the optimal conditions, the PtNiO/MWCNTs/GCE displayed wide linear dynamic ranges of 0.5-300 μM and 1.0-240 μM with

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low detection limits of 0.035 μM and 0.084 μM toward EP and TR, respectively. The proposed

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sensor has several advantages including high effective surface area, comfortable preparation,

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excellent sensitivity, stability and satisfiable reproducibility towards EP and TR determination. The results suggested that the Pt-NiO/MWCNTs/GCE is a hopeful sensor to determine EP and

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TR in biological and pharmaceutical samples with a significant recovery.

Keywords: Pt doped NiO nanoparticles; Multi-walled carbon nanotubes; Epinephrine; Tramadol.

1. Introduction

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Journal Pre-proof Epinephrine (EP), known as adrenaline, is the main catecholamine neurotransmitter that is involved significantly in the mammalian central nervous system and hormones [1]. EP is a firstline pharmacologic drug, which has been known as an effective treatment for anaphylaxis in emergencies [2, 3]. Besides, the effects of adrenaline on the reduction of postoperative bleeding and post-tonsillectomy pain are one of the strategies, which have been developed [4]. Different methods have been employed for determination of EP in biological and pharmaceutical samples

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such as spectrophotometry [5, 6], high performance liquid chromatography (HPLC) [7, 8], flow-

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injection chemiluminescence [9, 10], capillary electrophoresis [11], thermal lens microscopy

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(TLM) [12], fluorimetry [13] and electrochemiluminescence [14]. These procedures regularly

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have some drawbacks like time-consuming analysis, being expensive and tedious sample pretreatment steps. However, electrochemical procedures are favored to determine EP because of

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their advantages such as high sensitivity, low response time, inexpensive, less interference,

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simplicity, and without tedious procedures [15, 16]. Tramadol (TR) is considered a centrally acting analgesic. It is used as a non-steroidal anti-

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inflammatory drug with mild opioid agonist properties for treatment of moderate to severe pain

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[17, 18]. Besides its systemic influence, clinical and laboratory studies have reported the local anesthetic effect of TR on peripheral nerves [19, 20]. Some analytical procedures have been prospered to determine TR in several matrices, including HPLC [21, 22], liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) [23], gas chromatography with mass spectrometry (GC-MS) [24, 25], flow injection with multiple pulse amperometric detection (FIA–MPA)

[26],

spectrophotometry

[27],

and

capillary

Electrophoresis

with

electrochemiluminescence detection [28]. However, according to the mentioned advantages of

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Journal Pre-proof electrochemical methods respect to other analytical techniques, some electrochemical procedures have been suggested to determine TR [29, 30]. Some studies have reported that TR 5% plus adrenaline was capable of providing safe and efficient local anesthesia during circumcision and postoperative periods in children [31]. Other studies argued that submucous TR 50 mg enhanced the anesthetic effectiveness of mepivacaine with EP without extending the duration of anesthesia of soft tissue [32]. Still, other investigations

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indicated that TR mixed with adrenaline could be applied as an alternative local anesthetic in

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oral and maxillofacial surgery, particularly when the conventional local anesthetic method

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cannot be done [33]. Consequently, quick and reliable simultaneous determination of EP and TR

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is very important for efficient therapy and controlling of these drugs. Electrochemical sensors are a mighty choice for the simultaneous analysis of electro-active

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drugs in biological fluids and pharmaceutical products [34, 35]. To use the unmodified electrodes

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for electrochemical detection drugs in real samples, electrochemists should mount hard challenges. Carbon nanotubes (CNTs) have distinctive characteristics like small dimensions,

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large surface area, good electrical conductivity, chemical stability and sensitivity; therefore, they

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have been used favorably as a modifier in electrochemical sensors [36, 37]. Recently, the carbon composite sensors have performed better via surface modification by numerous types of nanomaterials [38, 39]. Among these, metal oxide nanostructures such as ZnO [40], CuO [41], SnO2 [42] and NiO [43] and others have been widely utilized in sensors. Nanostructured nickel oxide (NiO) is considered one of the most important transparent p-type semiconducting metal oxides with a wide band gap in the range of 3.6 eV- 4.0 eV for sensor applications due to their excellent catalytic activities, high conductivities, low cost, abundant sources, low toxicity and environmentally benign nature [44, 45]. Therefore, nanostructured

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Journal Pre-proof NiO has been proved a promising modifier in electrochemical sensors for highly sensitive detection of numerous important compounds such as; Nitrite [46], urea [47] and dopamine [48]. Doping of metal oxide semiconductor is capable of generating either a surplus or a deficiency in number of valance electrons, which could be capable of modulating the conductivity of the semiconductor. Doping with noble metals like Au [49], Ag [50], Pd [51] and Pt [52] increases the active surface area and improves the electronic properties of the NiO nanostructures, which

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can lead to higher sensor response than that of pure NiO. Among the noble metals, doping with

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platinum is believed to boost the electro-catalytic activity of the NiO nanostructures [53].

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In this work, a novel nanocomposite based on Pt doped NiO/MWCNTs modified glassy carbon

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electrode (Pt-NiO/MWCNTs/GCE) is proposed for fast and trustworthy determination of EP and TR simultaneously. As far as we know, there has been no investigation on the simultaneous

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determination of EP and TR yet. The Pt-NiO/MWCNTs/GCE exhibited superior electro-catalytic

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activity, high sensitivity, low response time, and good stability. In addition, this sensor was

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2. Experimental

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successfully used to determine EP and TR simultaneously in real sampels.

2.1. Chemicals and reagents

Nickel (II) nitrate hexahydrate (Ni(NO3)2.6H2O), (NH4)2[PtCl6], sodium hydroxide and TR were purchased from Sigma-Aldrich Co. EP was supplied from ACROS Co. MWCNTs (purity > 95%) with the tube length of 1–10 μm and number of walls of 3–15 were supplied from Plasma Chem GmbH Co. The phosphate buffer solution (PBS) as a supporting electrolyte was prepared from 0.1 M KH2PO4 and 0.1 M K2HPO4 solutions for adjusting pH values. Stock standard solutions of 0.01 M EP and 0.01 M TR was newly prepared in 0.1 M PBS (pH 7.0). All

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Journal Pre-proof of the chemicals were of analytical reagent grade and applied with no purifications. All solutions were prepared using double distilled water. Tramal®50 mg/mL and Adernalin®1 mg/mL injection solutions were purchased from a local pharmacy and used for real sample analysis without any further pretreatment. Fresh human urine and blood serum samples were supplied by a local

pathology clinic. About 10 mL of the blood serum and urine samples were centrifuged; then, after filtering, they were diluted 10-times with phosphate buffer solution of pH 7 and applied to

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determine spiked EP and TR in real sample without any further pretreatment.

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2.2. Apparatus

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Voltammetric investigations were done using a regular three‒electrodes system including the PtNiO/MWCNTs/GCE electrode as the working electrode, a platinum rod as an auxiliary electrode

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and saturated Ag/AgCl electrode as the reference electrode. DPV, CV, CA experiments were

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done by applying an Autolab PGSTAT 30 Potentiostat/Galvanostat (EcoChemie, The Netherlands). A Metrohm 744 pH meter and a combined glass electrode were applied for the pH

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measurements of the PBS. The XRD patterns were registered by X-ray diffraction instrument

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(PHILIPS, model PW1730) with Cu Kα radiation (λ = 1.5406 Å) in the step size 0.05 (°2Th.) and scan step time 1.00 s. The corresponding detection limit of the method was 2 wt%. A field effect scanning electron microscope (FESEM, TESCAN, model MIRA III) was used for morphological investigation.

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Journal Pre-proof 2.3. Synthesis of Pt doped NiO Nanoparticles The synthesis of Pt doped NiO nanoparticles was done by a simple sol-gel procedure. Briefly, 0.03g of ammonium hexachloroplatinate was added to 50 mL Ni(NO3)2.6H2O (0.5 M) solution. Afterward, 0.2 g starch was dissolved in 20 mL of deionized water at 40 ºC for 10 min entirely; then, the two solutions were mixed and stirred for 45 min at room temperature. sodium hydroxide (1.0 M) was added dropwise to the solution uninterruptedly until the pH reached 9 and

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mixed under vigorous stirring for 3.0 h. Then, the resulting light-green gel was washed and

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centrifuged continually in deionized water and ethanol to remove any impurities; it was put to

2.4. Preparation of Pt-NiO/MWCNTs/GCE

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dry in a vacuum oven at 70 ºC for 24 h and then calcinated at 500 ºC for 3h.

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In the first step, the GCE surface was polished using an aqueous slurry of 0.3 and 0.05μm of

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alumina, which was rinsed thoroughly with double-distilled water. Thereafter, it was sonicated in a 1:1 mixture of water-ethanol for 5 min and then dried under a nitrogen gas flow. In the next

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step, the amounts of Pt doped NiO nanoparticles and MWCNTs in dimethylformamide (DMF)

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were altered to reach the highest sensitivity of the sensor. According to the results, it was possible to have the best sensitivity for the modified electrode through a suspension mixture of 10% Pt doped NiO and 90% MWCNTs in dimethylformamide (DMF). In order to coat the surface of GCE, 20 μL of prepared suspension was cast on the cleaned GCE surface and the electrode let to dry at room temperature to achieve the Pt doped NiO/MWCNTs modified glassy carbon electrode (Pt-NiO/MWCNTs/GCE).

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Journal Pre-proof

3. Results and discussion 3.1. Characterizing Pt doped NiO/ MWCNTs nanocomposite To investigate the surface morphology of the NiO and Pt doped NiO nanoparticles the FESEM images were used (Fig. 1a, b). According to these images, similar observations have been seen on both the samples, except that the increase in Pt doping leads to decrease in

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nanoparticle size. Fig. 1c illustrate FESEM images of Pt doped NiO/MWCNTs nanocomposite.

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According to this image, the Pt doped NiO nanoparticles are well distributed on the MWCNTs

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surface.

Fig. 2a exhibits the XRD pattern of pure NiO nanoparticles and the prominent peaks at 37.20,

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43.30, 63.10, 75.60 and 79.40, which can be well corresponding to the diffraction of NiO with

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cubic structure from (111), (200), (220), (311) and (222) planes (JCPDS No. 73-1523),

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respectively [54]. The XRD pattern of Pt doped NiO nanoparticles is shown in Fig. 2b. As can be seen, no trace of platinum as pure metal, platinum oxides or any binary phases were observed.

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However, upon adding up the dopant, the decrease in the intensity of diffraction peaks,

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accompanied by a small broadening in the width has been observed. This can due to the decrease of nanoparticle size. This result corresponds with the FESEM results. Therefore, it is believed that the Pt ions could be substituted for the Ni ions and incorporated into NiO nanostructures with no alteration in its rutile structure [52]. Figs. 2c and 2d display the EDX investigations of the Pt doped NiO nanoparticles and Pt-doped NiO/MWCNTs nanocomposite. According to Fig. 2c, the EDX investigation of the Pt doped NiO nanoparticles showed the existence of Ni, O, and Pt. This result demonstrates that Pt ions are successfully doped into the NiO nanoparticles, although for Pt no XRD diffraction peaks were observed in Fig. 2b. According to Fig. 2d, the

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Journal Pre-proof EDX investigation of the Pt-doped NiO/MWCNTs nanocomposite showed the existence of C, Ni, O, and Pt. The presence of Ni, O, and Pt peaks along with of C peak verified that MWCNT was successfully modified with Pt doped NiO nanoparticles.

Please insert Fig. 1 here

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Please insert Fig. 2 here

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3.2. Electrochemical studies of modified Pt-NiO/ MWCNTs/GCE

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To investigate electrochemical performance of Pt-NiO/MWCNTs/GCE, CV experiments were carried out using 4 mM K3[Fe(CN)6] containing 0.1 M KCl as a redox probe at the surface of

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GCE, MWCNTs/GCE, NiO/MWCNTs/GCE and Pt-NiO/MWCNTs/GCE (Fig. 3). As shown Pt-

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NiO/MWCNTs/GCE displayed excellent improvement in redox peak current for [Fe(CN)6]3−/4− pair compared to NiO/MWCNTs/GCE, MWCNTs/GCE and GCE (Fig. 3). The cyclic

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voltammograms were applied at different scan rates to study the impact of amplification of the

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electrode on active surface area (Supplementary data Fig. S1). The [Fe(CN)6]3−/4− redox system and the Randles–Sevcik equation for a reversible process were applied to estimate the active surface areas of modified and unmodified electrodes [55]: Ipa = (2.69 × 105) An3/2D1/2C0υ1/2

(1)

Pursuant to Randles-Sevcik equation and the slopes of Ipa versus υ1/2 (Fig. S2), the active surface areas of MWCNTs/GCE, NiO/MWCNTs/GCE, and Pt-NiO/MWCNTs/GCE were calculated about 10.01, 14.27, and 20.88 times more than the GCE electrode, respectively.

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Journal Pre-proof Consequently, Pt doped NiO/MWCNTs were able to boost the effectiveness of the modifier on the GCE by increasing active surface area and facilitating the electron transfer. Please insert Fig. 3 here

3.3. Effect of supporting electrolyte and pH of supporting electrolyte The electrochemical responses for EP and TR at the Pt-NiO/MWCNTs/GCE were investigated

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in different electrolyte solutions including 0.1 M of phosphate buffer solution (PBS), citrate

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buffer solution (CBS) and acetate buffer solution (ABS) using DPV method (Fig. S3). The best

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sensitivity and peak shapes for EP and TR were obtained in 0.1M PBS. Accordingly, it was

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chosen as the optimum supporting electrolyte for further voltammetric measurements in simultaneous analysis of EP and TR on the surface of the Pt-NiO/MWCNTs/GCE.

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The DPV method was implemented in 0.10 M PBS to study the influence of pH of the

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supporting electrolyte on peak currents and potentials at the Pt-NiO/MWCNTs/GCE (Fig.4). As shown in Fig. 4a, the anodic peak currents (Ipa) increased from pH 4.0 to 7.0 and 4.0 to 8.0 for

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EP and TR, respectively, and then decreased gradually with a decrease in pH values. Thus, PBS

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with a pH of 7.0, which is close to biological pH value, was applied for subsequent experiments. Moreover, the results indicated that variation the anodic peak potentials (Epa) of EP and TR with pH is linear (Fig. 4b) as follows: EP: Epa (V) = − 0.069 pH + 0.624 (R2= 0.998) TR: Epa (V ) = − 0.067 pH + 1.126 (R2= 0.992) From the plot of Epa vs. pH, slopes of −0.069 and −0.067 were determined for EP and TR, respectively, which are close to the Nernstian value of 0.059 V/pH. These results suggest that the

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Journal Pre-proof number of transferred electrons and protons in the electro‒oxidation process of EP and TR are equal on the surface of the amplified electrode as offered earlier [56, 57].

Please insert Fig. 4 here

3.4. Effect of accumulation time

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The effect of accumulation time (tacc) on the anodic peak currents of TR and EP were studied

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to achieve the highest sensitivity in an operational condition (Fig. S4). According to the results

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indicated, the anodic peak current of EP and TR increased with accumulation time up to 50 s for

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EP and up to 60 s for TR and then leveled off at higher accumulation times because of saturation

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optimal time for further analyses.

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of the electrode surface with EP and TR. Thus, an accumulation time of 60 s was set as an

3.5. Electrochemical behavior of EP and TR at the surface of various electrodes

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Fig. 5 displays DPV responses of a mixture of 8 μM EP and 12 μM TR in PBS (pH 7.0) at GCE,

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MWCNTs/GCE, NiO/MWCNTs/GCE and Pt-NiO/MWCNTs/GCE. As shown, The PtNiO/MWCNTs/GCE shows highest oxidation peaks for EP and TR in comparison with other electrodes.The highest peak currents at Pt-NiO/MWCNTs/GCE were attributed to largest surface area and the highest electrical conductivity of Pt doped NiO/MWCNTs nanocomposite. Moreover, Pt-NiO/MWCNTs/GCE reveals the potential shift to lowest positive that could be because of the highest electro-catalytic behavior of Pt doped NiO/MWCNTs nanocomposite on oxidation of EP and TR. Hence, the Pt-NiO/MWCNTs/GCE was applied for enhanced electrochemical determination of EP and TR simultaneously.

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Journal Pre-proof Please insert Fig. 5 here

3.6. Effect of scanning rate To investigate the influence of scan rate on the oxidation peak currents (Ipa) and oxidation potential (Epa) of EP and TR at the surface of the Pt-NiO/MWCNTs/GCE, CV experiments were carried out (Figure 6). It is possible to acquire valuable information involving electrochemical

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mechanism from CV experiments through the investigation of the relevance between the peak

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currents (Ipa) and scan rate (υ). The anodic peak currents of EP and TR showed a linear

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relationship with the scan rate (υ) over the range of 10 to 200 mV s−1 (Fig. S5). The corresponding linear regression equations are as follows: R2 = 0.993

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EP: Ipa (µA) = 0.929 υ (mV s−1) + 24.47

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TR: Ipa (µA) = 0.895 υ (mV s−1) + 24.81 R2 = 0.994

processes at those scan rates.

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According to these results, electron-transfer reactions of EP and TR were adsorption-controlled

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At sweep rates from 200 to 400 mV s−1, the anodic peak currents were linked linearly to the

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square root of scan rate (υ1/2) showing the oxidations of EP and TR at proposed electrode surface were diffusion controlled processes (Fig. S6). The corresponding linear regression equations are as follows: EP: Ipa (A) = 14.86 υ1/2 (mV s−1)1/2 − 10.16

R2 = 0.998

TR: Ipa (A) = 15.69 υ1/2 (mV s−1)1/2 − 28.73 R2 = 0.998 Therefore, the results confirmed both adsorption and diffusion control during electrochemical reaction of EP and TR at the surface of Pt-NiO/MWCNTs/GCE

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Journal Pre-proof For an irreversible anodic reaction, the electron transfer rate constant (ks) and charge transfer coefficient (α) can be obtained by determining the difference of Ep versus lnʋ using Laviron’s theory, and followed by the following equations [58]: Ep = E0 – (RT/αanF) ln (RTKs / αanF) + (RT/αanF) lnʋ

(2)

It is possible to determine the formal potential (E˚) from the intercept of Ep versus ʋ curve by

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extrapolating to the vertical axis at ʋ=0 [59]. The values of αa for EP and TR were calculated to

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be 0.46 and 0.44, respectively, by considering the slope of the straight line of Ep versus lnʋ (inset of Fig. 5). Using E˚ and αa values, the values of Ks for EP and TR were calculated to be 0.87

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s−1and 0.52 s−1respectively. The high value of Ks indicated the significant capability of the Pt-

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NiO/MWCNTs nanocomposite to elevate electron transfer between the EP, TR and the electrode

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surface.

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Please insert Fig. 6 here

3.7. Calibration curve and limits of detection

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To study the proposed sensor in terms of analytical performance and determine EP and TR quantitatively, DPV technique was applied using Pt-NiO/MWCNTs/GCE with simultaneously changing the concentrations of EP and TR in 0.1M PBS with pH 7.0 (Fig. 7). The calibration plot of the mixture of EP and TR are shown in Figs. 7a and b, in the respective order. As shown, the oxidation peak currents were proportionate to EP and TR concentrations in the range of 0.5– 300 μM with a linear regression equation Ipa (µA) = 1.139 CEP (µM) + 5.901 (R2 = 0.997) and 1.0–240 μM with a linear regression equation Ipa (µA) = 0.537 CTR (µM) + 3.190 (R2 = 0.998) respectively. Also, the detection limits were calculated to be 0.035 μM and 0.084 μM for EP and 13

Journal Pre-proof TR, respectively (S/N=3). According to the results, Pt-NiO/MWCNTs/GCE is capable of providing high sensitivity and wide linear dynamic range with low detection limit. Please insert Fig. 7 here

3.8. Repeatability and stability of the Pt-NiO/MWCNTs/GCE

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The repeatability of the proposed sensor was investigated by successive determinations (n =

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10) of 60 μM EP and 100 μM TR solution using DPV method under optimum conditions. The

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relative standard deviations (RSDs) were obtained 2.67% and 3.54% for EP and TR,

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respectively. According to the results, the Pt-NiO/MWCNTs/GCE was not subjected to surface contaminate during the voltammetric analysis that makes the sensor excellent in terms of

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repeatability. To study the stability of the Pt-NiO/MWCNTs/GCE under wet condition, DPV

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experiments of EP and TR were carried out after immersion of the modified electrode in 0.1M PBS (pH 7.0). It was found that the Pt-NiO/MWCNTs/GCE was subjected to six experiments

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during 12 h leading to a less than 4.7% and 5.3% reduction in the DPV responses of EP and TR,

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respectively. In addition, by keeping the modified electrode in the air for 10 days (about 5 measurements), the oxidation peak currents of EP and TR at the Pt-NiO/MWCNTs/GCE retained 92.6% and 90.8% of their initial response values, respectively, which confirms the high stability of the Pt-NiO/MWCNTs/GCE for sensing of EP and TR (Fig. 8). Please insert Fig. 8 here

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Journal Pre-proof 3.9. Interference studies The effects of some the usual interfering species on the sensing of 60 μM EP and 100 μM TR at the Pt-NiO/MWCNTs/GCE were examined under optimum conditions using DPV technique (Fig. S7). The tolerance limit for each interfering species is shown in Table 1; it was taken as the concentration of the interferent that gives an error less than 10% in peak current of target analytes. The results reveal that the usual interfering species did not influence the sensing of EP

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and TR in biological samples and pharmaceutical formulations at the proposed sensor

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significantly.

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Please insert Table 1 here

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3.10. Real sample analysis

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To investigate the capability of the Pt-NiO/MWCNTs/GCE for the determination of EP and

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TR in biological samples and pharmaceutical formulations, the standard addition method was examined using DPV method. The application of the standard addition method excludes matrix

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effect during measurements. The electrochemical outcomes were compared with HPLC results as

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a reference method. Statistical calculations were indicated that both methods are in good agreement with no significant difference for the 95% confidence level. Tables 2 and 3 represent the results. Significant recoveries were observed from spiked samples indicating that proposed method is valid to determine of EP and TR simultaneously in real samples with no need for special pretreatments and using time-consuming analysis. Please insert Table 2 here Please insert Table 3 here

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Journal Pre-proof 4. Conlusion In summary, the Pt doped NiO/MWCNTs was introduced as a novel sensing platform for constructing a highly-sensitive voltammetric sensor based on modified glassy carbon electrode to

determine EP and TR simultaneously. The responses of the Pt-NiO/MWCNTs/GCE were significantly improved for EP and TR compared to the NiO/MWCNTs/GCE because of Pt ions doping into NiO matrix that increase the active surface area and improve the electro-catalytic

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properties of the NiO nanoparticles. Table 4 compares the electrochemical parameters of the

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proposed sensor to determine EP and TR with those reported previously. The proposed sensor

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showed wide linear range with comparable detection limit to determine EP and TR

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simultaneously. In addition, the proposed sensor presented the simple and cost-effective preparation process, high sensitivity and stability, good repeatability, high tolerance limit for

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common interfering agents and satisfactory recovery to determine of analytes in real samples

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feasible applications.

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which can recommend Pt-NiO/MWCNTs/GCE as a excellent and marvelous candidate for

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Please insert Table 4 here

Acknowledgment The authors gratefully acknowledge the research council of Arak University for providing financial support (No. 98.662) for this work.

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Journal Pre-proof References

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[14] Y. Su, J. Wang, G. Chen, Determination of epinephrine based on its enhancement for electrochemiluminescence of lucigenin, Talanta 65 (2005) 531-536.

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[15] S. Bahmanzadeh, M. Noroozifar, Fabrication of modified carbon paste electrodes with Ni-

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crystal/carbon nanotubes-based electrochemical sensor, J. Electroanal. Chem. 839 (2019) 48-58

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Journal Pre-proof Figure captions Fig. 1 FESEM images of the pure NiO nanoparticles (a) , Pt doped NiO nanoparticles (b) and Pt doped NiO/MWCNTs nanocomposite (c). Fig. 2 The XRD patterns of the pure NiO nanoparticles (a) and Pt doped NiO nanoparticles (b) and EDX spectrums of the Pt doped NiO nanoparticles (c) and Pt doped NiO/MWCNTs nanocomposite (d).

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Fig. 3 Cyclic voltammograms of 4 mmol L–1 K3[Fe(CN)6] containing 0.1 M KCl on GCE,

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MWCNTs/GCE, NiO/MWCNTs/GCE and Pt-NiO/ WCNTs/GCE; scan rate 0.1 V s−1, tacc

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= 60 s.

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Fig. 4 DPVs of Pt-NiO/MWCNTs/GCE in 60 μM EP and 100 μM TR (0.1 M PBS, pH: 4, 5, 6,

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7, 8, 9); scan rate 0.01 V s–1. Insets: effect of pH on the peak currents (a) and peak potentials (b).

DPV voltammograms of GCE, MWCNTs/GCE, NiO/MWCNTs/GCE and Pt-NiO/

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Fig. 5

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tacc= 60 s.

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MWCNTs/GCE for 8 μM EP and 12 μM TR in 0.1M PBS (pH 7.0); scan rate 0.01 V s–1,

Fig. 6 Cyclic voltammetry curves of Pt-NiO/MWCNTs/GCE in 60 μM EP and 100 μM TR at different scan rates (10 ‒ 400 mV s–1), Inset: Plot of Ep vs. lnʋ for EP and TR. Fig. 7 DPVs of Pt-NiO/MWCNTs/GCE in various concentrations of EP and TR in buffer solution. Insets: Plot of linear dependence of peak current with EP concentrations (a). Plot of linear dependence of peak current with TR concentrations (b). Fig. 8. The oxidation peak currents for 60 μM EP and 100 μM TR at Pt-NiO/ MWCNTs/GCE in different days (Days; 1, 3, 5, 7, 10). 26

Journal Pre-proof Table1. Maximum tolerable concentrations for usual interfering species EP

TR

Cint/(µM)

Cint/(µM)

L-cysteine

650

400

L-Glutamic acid

500

600

Ascorbic acid

450

800

Uric acid

150

550

Codeine

500

100

Acetaminophen

300

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Interference

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450

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na

lP

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Cint refers to interfering species concentration.

27

Journal Pre-proof Table 2. Results of EP and TR determination (µM) in human serum and urine samples.

Human urine

TR

EP

TR

EP



—

—


105.0

96.2

—

—

2.00

2.00

1.89±0.11

2.10±0.13

94.5

4.00

4.00

4.13±0.09

3.85±0.14

103.2

—

—



—

2.00

2.00

2.11±0.09

2.15±0.12

105.5

4.00

4.00

3.83±0.16

4.12±0.08

95.7

na

lP

re

Average of three determinations at optimum conditions. The theoretical values of F and t at p = 0.05 are 39 and 2.78, respectivel

ur

b

Reference method Founda (µM)

EP

Jo

a

TR

—

107.5

ro

Human serum

EP

Proposed method Recovery (%)

103.0

-p

Spiked (µM)

Proposed method Founda (µM)

28

TR

F-testb (%)

EP

TR

t-testb (%)

EP

TR

—

—

—

—

2.08±0.09 1.92±0.07

1.49

3.45

2.32

2.11

4. 07±0.05 4.09±0.09

3.24

2.42

1.01

2.49

—

—

—

—

2.05±0.04 1.95±0.07

5.06

2.94

1.05

2.50

4.08±0.09 3.94±0.11

3.16

0.53

2.35

2.29


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Added (µM)



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Table 3. Results of EP and TR determination (µM) in injection samples. Added (µM)

Spiked (µM)

EP

TR

Injection

—

—

1.56±0.08

1.72±0.06

95.3

1.00

1.00

2.70±0.11

2.59±0.09

2.00

2.00

3.52±0.13

3.57±0.15

TR

EP

TR

Reference method Founda (µM) EP

EP

TR

EP

TR

2.56

0.44

0.92

2.08

102.4

97.1

2.57±0.08 2.63±0.05

1.89

3.24

1.35

0.67

96.8

97.3

3.71±0.11 3.62±0.07

1.40

4.59

1.93

0.52

ro -p re lP na

t-testb (%)

1.61±0.05 1.59±0.09

Average of three determinations at optimum conditions. The theoretical values of F and t at p = 0.05 are 39and 2.78, respectively

29

TR

F-testb (%)

103.2

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EP

ur

b

Proposed method Recovery (%)

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a

Proposed method Founda (µM)

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Table 4. Comparison of the response characteristics of the EP and TR at different modified electrodes

Modifier

Method

Analyte

carbon film

MWCNT in a chitosan matrix

DPV

EP

10-100

0.9

Not reported

No

No

Yes

[60]

Glassy carbon

nickel oxide nanoparticles and carbon nanotubes within a dihexadecylphosphate film

DPV

EP

0.3-9.5

0.082

0.54

Yes

No

No

[38]

Glassy carbon

hybrid material SiO2/graphene Oxide content Ag nanoparticles

SWV

2.0-8.0

0.27

Not reported

Yes

No

No

[61]

Gold

AgNPs-penicillamine

CA

EP

0.1-100

0.49

Yes

No

No

[62]

screen printed

ZnO -graphene oxide nanocomposite

DPV

EP

0.5-500

0.07

Not reported

No

Yes

Yes

[63]

Carbon paste

Ni-doped Lewatit FO36 nano ion exchange resin

DPV

EP

7 -560

-p

0.45

0.75

Yes

Yes

No

[15]

Glassy carbon

molecularly imprinted polymer (MIP)/gold nanoparticles (AuNPs) composite

DPV

EP

0.09-100

re

0.076

Not reported

No

No

Yes

[16]

Platinum

poly 1,8diaminonaphthalene derivative

TR

5-30

0.327

Not reported

Yes

No

Yes

[29]

Carbon paste

NiFe2O4/graphene nanocomposite

TR

0.01 -9.0

0.0036

Not reported

Yes

Yes

No

[64]

Glassy carbon

poly(Nile blue)

DPV

TR

1.0 - 310

0.5

Not reported

No

No

No

[65]

pencil graphite

—

DPV

TR

0.1-1.1

0.0038

0.43

Yes

No

No

[66]

magneto layer double hydroxide (LDH)/Fe3O4

DPV

TR

1.0-200

0.03

Not reported

Yes

Yes

No

[67]

Nafion-coated tetrahedral amorphous

DPV

TR

1.0-12.5

0.13

Not reported

Yes

No

No

[30]

nanocobalt oxide/ionic liquid crystal/carbon nanotubes

DPV

TR

0.06-10

0.62× 10–3

Not reported

No

No

No

[68]

EP TR

0.5-300 1.0-240

0.035 0.084

0.46 0.44

Yes

Yes

Yes

This work

Tetrahedral amorphous

carbon Carbon paste

Pt doped NiO/MWCNTs DPV nanocomposite SWV: Square wave voltammetry; CA: Chronoamperometry

Glassy carbon

0.0005

ro

lP

na SWV

ur

Jo

Glassy carbon

SWV

of

Electrode

EP

LOD / (µmol L-1)

Charge Analytical Sample transfer Serum coefficient or Urine Injection (α) Plasma

LDR / (µmol L-1)

.

30

Ref

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Fig. 1

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Fig. 3

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Fig. 4

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Fig. 5

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Fig. 6

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Fig. 8

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Journal Pre-proof Credit Author Statement: Aliyeh Dehdashti: Investigation, Methodology, Validation, Writing - Original Draft

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Ali Babaei: Supervision, Conceptualization, Writing - Review & Editing

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Journal Pre-proof Declaration of interests

 The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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☐The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:

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Journal Pre-proof Highlights  A novel sensing platform based on Pt doped NiO/MWCNTs was designed as the modifier. 

Modified glassy carbon electrode used to determine epinephrine (EP) and tramadol (TR) simultaneously.



The sensor showed electro-catalytic activities towards the electro‒oxidation process of EP and TR.

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 The proposed sensor was applied for enhanced sensing of both analytes in real samples.

42