Electrochemical Determination of Diclofenac by Using ZIF-67/ g- C 3 N 4 Modified Electrode

Abstract

A facial differential pulse voltammetric procedure using a glassy carbon electrode modified with zeolite imidazolate framework-67/graphitic carbon nitride (ZIF-67/g-C₃N₄) for the diclofenac (DCF) determination is demonstrated. ZIF-67/g-C₃N₄ with different mass ratios of the components was synthesized in a self-assembly process. The obtained materials were characterized by using X-ray diffraction, scanning electron microscopy (SEM), EDX-mapping, and nitrogen adsorption/desorption isotherms. The peak current varies linearly with the DCF concentration in the range of 0.2–2.2 μmol·L⁻¹ and has a detection limit of 0.071 μmol·L⁻¹. The modified electrode exhibits acceptable repeatability, reproducibility, and selectivity towards DCF. The proposed electrode allows determining DCF in human urine without pretreatment, and the results are comparable with those determined with HPLC.

1. Introduction

Diclofenac, 2-(2 $^{'}$ ,6 $^{'}$ -dicholoroanilino) phenylacetic acid (denoted as DCF), is used for the treatment of several diseases, such as ankylosing spondylitis, rheumatoid arthritis, and osteoarthritis [1]. However, diclofenac causes acute hepatotoxicity, and this chemical-driven liver damage leads to the change in the kidney function and gills in rainbow trout (O. mykiss). Diclofenac also presents acute toxicity to phytoplankton and zooplankton. Moreover, the possible synergetic effects with other pharmaceuticals or chemicals in the aquatic environment increase the environmental risk [2]. Various techniques have been developed to determine diclofenac because of the prominence of DCF in the environment and pharmaceutical and clinical applications. The techniques include capillary zone electrophoresis with electrochemical detection [3], high-performance liquid chromatography (HPLC) [4], HPLC combined with solid-phase extraction [5], and spectrofluorimetry [6]. Besides these techniques, electrochemical methods possess several advantages, such as high sensitivity, selectivity, and quick, cheap analysis for actual samples. These techniques use various types of porous materials to modify the working, such as ionic liquid/carbon nanotube-paste electrode [7], carboxyl/multiwalled carbon nanotubes/screen-printed carbon electrode [8], and gold/multiwalled carbon nanotube/glassy carbon electrode [9].

Zeolite imidazolate framework-67 (ZIF-67) is a subclass of metal-organic frameworks (MOFs). It is an organic-inorganic hybrid solid with infinite and uniform crystalline coordination networks consisting of cobalt ions (II) and imidazolate ligands [10]. ZIF-67 exhibits various unique properties, such as thermal and chemical stability, high surface area, large pores, accessible coordinative unsaturated sites, and excellent chemical and solvent stability [10]. At present, ZIF-67 attracts increasing attention from researchers in various fields, such as adsorption and separation [11], catalysis [12], and gas separation [13]. However, its poor electroconductivity leads to limited applications in electrochemistry [14]. Graphitic carbon nitride (g-C₃N₄) with graphitic-like structure possesses a unique ability to be simply prepared by thermally condensation of cheap nitrogen-rich compounds such as urea, melamine, and cyanimide [15, 16], and this is unlike graphene, reduced graphene oxide, and graphitic oxide that require the more complex synthesis processes. It has gradually attracted attention in multidisciplinary areas due to its characteristic physicochemical properties, such as ability to resist attacks from strong acid/alkaline solution [17], moderate bandgap (~2.7 eV), and superior electronic properties [18]. Therefore, the combination of highly electroconductive g-C₃N₄ with large surface area ZIF-67 might lead to versatile materials with properties of both components.

To the best of our knowledge, only a few papers have been reported on the voltammetric or amperometric detection of DCF on a ZIF-67/g-C₃N₄ modified electrode. Therefore, to fabricate new electrodes, we expand our research on modifying glassy carbon electrodes (GCE). In the present work, we describe the determination of DCF by using a GCE electrode modified with ZIF-67/g-C₃N₄. This modified electrode exhibits sound electrocatalytic and accumulative effects on DCF and enables us to determine the DCF content in human urine with satisfactory results.

2. Experimental

2.1. Materials

Melamine (C₃N₃(NH₂)₃), absolute ethanol (C₂H₅OH), methanol (CH₃OH), cobalt nitrate hexahydrate (Co(NO₃)₂·6H₂O), and 2-methylimidazole (CH₃C₃H₂N₂H) were purchased from Merck company. Diclofenac sodium salt (C₁₄H₁₀Cl₂NNaNO₂) was procured from Sigma-Aldrich. Acetic acid (CH₃COOH), phosphoric acid (H₃PO₄), boric acid (H₃BO₃), and potassium hydroxide (KOH) were purchased from Daejung (Korea).

The phosphate buffer solution (PBS) with pH 7 was prepared from 0.5 M Na₂HPO₄, 0.5 M KH₂PO₄, 0.5 M NaCl, and 0.5 M KCl solutions. The Britton–Robinson buffer solution (B–RBS) with pH 3–9 was prepared from 1 M H₃BO₃, 1 M H₃PO₄, and 1 M CH₃COOH solutions and adjusted with a 1 M KOH solution. The stock solution was prepared by dissolving 29.6 mg of diclofenac in a 10 mL volumetric flask containing a pH 6 buffer solution. The flask was subjected to ultrasonication in a cold water bath and stored in a refrigerator at 5°C. The stock sample was prepared 30 min before analysis.

2.2. Material Synthesis

ZIF-67 was synthesized according to Qian et al. [10]. Briefly, 1.16 g of Co(NO₃)₂·6H₂O and 1.31 g of 2-methylimidazole (Hmim) were dissolved in 100 mL of methanol separately. These two solutions were mixed so that the resulting mixture has the following molar composition: $C o^{2 +} / Hmim / C H_{3} OH = 1 : 4 : 1.2$ and stirred for 24 h at ambient temperature. Then, the purple solid (ZIF-67) was collected by centrifuging, washed with ethanol five times, and dried at 80°C for 24 h.

The g-C₃N₄ was synthesized according to Yan et al. [19]. In brief, 10 g of melamine powder was put into an alumina crucible with a cover and heated at 500°C in a muffle furnace for 2 h.

The ZIF-67/g-C₃N₄ was synthesized as follows: 0.5 g of the g-C₃N₄ and ZIF-67 mixture was distributed in 100 mL of ethanol under ultrasonication for 6 h. The ZIF-67/g-C₃N₄ mass ratio is as follows: 0 : 10, 3 : 7, 4 : 6, 5 : 5, 6 : 4, and 10 : 0. The samples are denoted as (0/10)ZIF-67/g-C₃N₄, (3/7)ZIF-67/g-C₃N₄, (4/6)ZIF-67/g-C₃N₄, (5/5)ZIF-67/g-C₃N₄, (6/4)ZIF-67/g-C₃N₄, and (10/0)ZIF-67/g-C₃N₄.

2.3. Instruments

The material was characterized by using X-ray diffraction (XRD) with a D8-Advance device (Bruker, USA; Cu Kα radiation, $λ = 1.5406 Å$ ), scanning electron microscopy (SEM) with JMS-5300LV (USA), Raman spectroscopy with Xplora Plus (Horiba with 785 nm laser excitation), transmission electron microscopy (TEM) with JEM-2100, and nitrogen adsorption/desorption isotherms with a Micromeritics 2020 volumetric adsorption analyzer system (the sample was degassed at 150°C for 12 h). The specific surface area was calculated according to the Brunauer–Emmett–Teller (BET) model. The meso/microsurface area was calculated with the $t$ -plot method. Electrochemical measurements were conducted with a CPA-HH5 computerized polarography analyzer (Vietnam). A three-electrode system consisting of a working electrode (GCE, 0.28 cm²), a reference electrode (Ag/AgCl in saturated KCl), and a counter electrode (platinum wire) was used for the measurements. The high-performance liquid chromatography (HPLC) was performed to measure DLF for the sake of comparison. The HPLC measurements were conducted on an HPLC Shimadzu with LC 20 AD pump, PDA SPD–M20A detector (Japan), C18 column ( $250 \times 4.6$ mm; particle size 5 μm). The mobile phase is a mixture of methanol/5 mM NaH₂PO₄ (pH 2.3) (66 : 34 v/v). The flow rate was 1 mL·min^–1 with an injection volume of 20 μL. For HPLC analysis, DCF detection was performed at a wavelength of 274 nm.

2.4. Preparation of Electrode and Actual Sample

2.4.1. Electrode Preparation

Prior to modification, the GCE was first polished with alumina slurry (0.05 μm) on a polishing pad, followed by successive ultrasonication in ethanol and distilled water. Then, the electrode was washed with double distilled water and dried at ambient temperature. The suspension of ZIF-67/g-C₃N₄ was prepared by mixing 10 mg of ZIF-67/g-C₃N₄ with 10 mL of ethanol under ultrasonication for 24 h. Five microliters of suspension was cast dropwise on the GCE surface and dried in an oven for a few minutes. The as-prepared electrode was denoted as ZIF-67/g-C₃N₄-GCE.

2.4.2. Real Samples

Human urine samples were received from five healthy persons aged 25–30 and stored in a refrigerator at 5°C. About 5 mL of the sample was filtered through a 0.2 μm membrane. One milliliter of the supernatant was collected and diluted with 2 mL of pH 6.5 BRS to avoid complex interference. The resulting solution was transferred to a 100 mL electrochemical cell for analysis.

3. Results and Discussion

3.1. Characterization of Materials

The XRD patterns of g-C₃N₄, ZIF-67, and ZIF-67/g-C₃N₄ are shown in Figure 1. Two peaks at around 13.7 and 27.1° are found in g-C₃N₄ ((0/10)ZIF-67/g-C₃N₄)). It is well known that g-C₃N₄ consists of tri-s-triazine building blocks [20]. The higher peak at 27.1° is assigned to the characteristic interlayer of aromatic systems, indexed for graphitic materials as (002), while the peak at 13.7°, indexed as (100), is attributed to the periodic arrangement of the condensed tri-s-triazine units in the sheets [21] (the inset of Figure 1). For the XRD pattern of (10/0)ZIF-67/g-C₃N_4, the characteristic peaks for ZIF-67 at 18.20, 30.22, 35.68, 43.28, 53.68, 57.18, and 62.76°, indexed as (111), (220), (311), (400), (422), (511), and (440) according to CCDC 671073, are clearly observed indicating that the (10/0)ZIF-67/g-C₃N₄ is ZIF-67. The intensity of these peaks in ZIF-67/g-C₃N₄ increases with an increase in the ZIF-67/g-C₃N₄ fraction. This increase manifests the coexistence of g-C₃N₄ and ZIF-67 phases in the composite. Clear characteristic peaks of ZIF-67 witness that the hybrid of ZIF-67 with g-C₃N₄ has no significant effects on the crystal structure of ZIF-67.

Figure 1

XRD patterns of ZIF-67, g-C₃N₄, and ZIF-67/g-C₃N (the inset presents the XRD partten of (0/10)ZIF-67/g-C₃N₄).

Nitrogen adsorption/desorption isotherms are employed to evaluate the samples’ specific surface area and porosity (Figure 2). The isotherm curves of ZIF-67 have a type I isotherm, indicating the presence of a microporous material. The g-C₃N₄ has a type IV isotherm with an H3 hysteresis loop at high relative pressure between 0.46 and 1.0, confirming the existence of a mesoporous structure. The BET surface area (S _BET) and total pore volume (V _pore) are listed in Table 1.

Figure 2

Nitrogen adsorption/desorption isotherms of ZIF-67, g-C₃N₄, and ZIF-67/g-C₃N₄.

Table 1

Textural properties of ZIF-67/g-C₃N₄.

Notation	$S_{BET}$ (m²·g^–1)	$S_{meso}$ (m²·g^–1)	$S_{micro}$ (m²·g^–1)	$V_{total}$ (cm³·g^–1)
(0/10)ZIF-67/g-C₃N₄	4.2	2.7	1.5	26.9
(3/7)ZIF-67/g-C₃N₄	335.6	25.1	310.5	140.4
(4/6)ZIF-67/g-C₃N₄	449.0	9.8	439.2	197.3
(5/5)ZIF-67/g-C₃N₄	492.0	10.5	481.5	178.2
(6/4)ZIF-67/g-C₃N₄	731.9	10.6	721.3	225.0
(10/0)ZIF-67/g-C₃N₄	1217.1	6.9	1210.1	400.6

Compared with pure ZIF-67, the ZIF-67/g-C₃N₄ has the $S_{BET}$ declining from 1217.1 to 335.6 m²·g^–1 as the amount of g-C₃N₄ increases. This decline might result from the low surface area of g-C₃N₄ and blockage of micropores of the increasing g-C₃N₄ amount in the composite. The primary test reveals that the (5/5)ZIF-67/g-C₃N₄ sample has the highest electrocatalytic activity for DCF oxidation. Therefore, (5/5)ZIF-67/g-C₃N₄ is selected for further experiments.

As shown in Figure 3(a), smooth rhombic dodecahedral-shaped crystals with 1.5 μm in width are observed for ZIF-67. The surface of g-C₃N₄ exhibits a layered and platelet-like morphology (Figure 3(b)). Although several inclusions of g-C₃N₄ appear on the ZIF-67 surface, the rhombic dodecahedral structure of ZIF-67 remains (Figure 3(c)). The TEM image illustrates a sheet-like structure of g-C₃N₄ embroiled with dark-colored ZIF-67 crystals (Figure 3(d)). These results indicate the coexistence of ZIF-67 and g-C₃N₄ via self-assembly.

Figure 3

(a) SEM image of ZIF-67, (b) TEM image of g-C₃N₄, (c) SEM image of ZIF-67/g-C₃N₄, and (d) TEM image of (5/5)ZIF-67/g-C₃N₄.

(b)

(c)

(d)

The ZIF-67/g-C₃N₄ structure is characterized by using Raman spectra (Figure 4). Typical characteristic peaks of g-C₃N₄ at 470, 543, 702, 746, 978, and 1147 cm^–1 are observed, and they are consistent with those in a previously published report [22]. The peaks at 702 and 978 cm^–1 indicate the existence of the heptazine ring structure [23]. The peak at 702 cm^–1 is ascribed to the inplane bending vibrations of the heptazine linkages, whereas the 978 cm^–1 peak is assigned to the symmetric N-breathing mode of the heptazine units [24]. For ZIF-67, characteristic peaks at 686, 831, 951, 1044, 1147, 1178, 1307, 1385, 1459, and 1506 cm^–1 are attributed to the cobalt ion [25], imidazolium ring puckering, δ H (out of plane), bending C–H (out of plane) (C4–C5), bending C–H (out of plane) (C2–H), stretching C–N, N–H wag, bending of CH₃, stretching of C2–N1, and stretching of C–H (methyl), respectively [26]. The characteristic vibrations of ZIF-67 and g-C₃N₄ in the Raman spectrum of ZIF-67/g-C₃N₄ confirm the coexistence of ZIF-67 and g-C₃N₄ again.

Figure 4

Raman spectra of (a) g-C₃N₄, (b) ZIF-67, and (c) ZIF-67/g-C₃N₄.

(b)

(c)

The elemental composition of ZIF-67/g-C₃N₄, derived from the EDX spectrum, is presented in Figure 5. As expected, the elements in (5/5)ZIF-67/g-C₃N₄ are only carbon (at 0.3 keV), nitrogen (0.4 keV), oxygen (0.6 keV), and cobalt (0.8; 7.0; 7.7 keV), indicating that the obtained material has high purity (Figures 5(a) and 5(b)). The EDX mapping of carbon (Figure 5(c)), cobalt (Figure 5(d)), nitrogen (Figure 5(e)), and oxygen (Figure 5(f)) on the ZIF-67/g-C₃N₄ surface shows that all these elements are not confined to a single site. Instead, they are distributed in the matrix.

Figure 5

EDX-mapping of electron image for ZIF-67/g-C₃N₄ (a, b), carbon element (c), cobalt element (d), nitrogen element (e), and oxygen element (f).

(b)

(c)

(d)

(e)

(f)

Although Figure 6 shows that ZIF-67 could attach to the surface of g-C₃N₄, such self-assembly can be further confirmed by studying the surface charges of ZIF-67, g-C₃N₄, and their composite (Figure 6). These values are determined with the drift pH method [27]. As seen from the figure, the material’s surface is positively charged when $pH < 9.2$ for ZIF-67 and $pH < 3.8$ for g-C₃N₄. Therefore, the electrostatic attraction between ZIF-67 and g-C₃N₄ could form ZIF-67/g-C₃N₄ with a positively charged surface at pH below 8.4.

Figure 6

Point of zero charge (pH_PZC) of (5/5)ZIF-67/g-C₃N₄, ZIF-67, and g-C₃N₄.

The stability of (5/5)ZIF-67/g-C₃N₄ in the solutions with different pHs is essential for the electrochemical application. Figure 7 presents the XRD patterns of (5/5)ZIF-67/g-C₃N₄ immersed in water with different pHs for 5 hours. At pH less than 4, the characteristic diffractions of ZIF-67 are absent, revealing that the material is destroyed at these pHs. The peaks of ZIF-67 remain in the solutions with pH 5–10, indicating that ZIF-67 is stable in this pH range.

Figure 7

XRD patterns of (5/5)ZIF-67/g-C₃N₄ at pH 2–10.

3.2. Electrochemical Determination of Diclofenac by Using (5/5)ZIF-67/g-C₃N₄

3.2.1. The Cyclic Voltammetry of DCF on (5/5)ZIF-67/g-C₃N₄ Modified Electrode (ZC-GCE)

The cyclic voltammograms (CVs) (Figure 8) are obtained in the presence of 5 mM DCF on GCE, ZIF-67-GCE, g-C₃N₄-GCE, and ZIF-67/g-C₃N₄-GCE in 0.2 M BRS pH 6. The bare GCE does not exhibit any electrochemical signals, indicating that this electrode cannot detect DCF. The modified electrodes (with ZIF-67, g-C₃N₄, or ZIF-67/g-C₃N₄) exhibit an oxidation peak of DCF at around 0.68 V. In particular, the ZIF-67/g-C₃N₄ modified electrode significantly enhances the electrochemical response, and the intensity of peak current depends on the ZIF-67 and g-C₃N₄ mass ratio. The (5/5)ZIF-67/g-C₃N₄-GCE (henceforth denoted as ZC-GCE) provides the highest intensity with a peak potential of 0.671 V. The peak current is 2.1-fold and 2.12-fold higher than that of g-C₃N₄/GCE and ZIF-67-GCE, respectively. The substantial enhancement in the anodic peak current clearly shows the catalytic effect of ZIF-67/g-C₃N₄. No reduction peaks are observed on the reverse scan, indicating that the electron transfer on the ZC modified electrode is irreversible. In addition, the ZC-GCE does not exhibit an oxidation/reduction peak on the voltammogram in the solution without DCF, indicating the ZC-GCE is inactive in the studied potential range.

Figure 8

Cyclic voltammograms of 5 mM DCF in 0.2 M BRB pH 6 on GCE, ZIF-67-GCE, g-C₃N₄-GCE, and ZIF-67/g-C₃N₄-GCE.

(1) Effect of pH. The influence of pH on the oxidation peak current of the $5.0 \times 10^{- 3}$ M DCF solution is studied by using CV in the BR buffer. At pH 3–5, DCF oxidation at the electrode is not observed. It is possibly due to the unstable structure of ZIF-67 in ZIF-67/g-C₃N₄ in this pH range (Figure 7). The peak current increases with pH and has the highest value at pH 6.5. Higher pHs witness a decrease of the peak current up to pH 8, and then the current increases again (Figure 9(c)). Therefore, pH 6.5 is selected for further experiments. The point of zero charge of ZIF-67/g-C₃N₄ is 8.4, and the pK _a of DCF is around 4 [28]. The pH dependence of peak currents of DCF oxidation could not be explained by the electrostatic interaction between charged species on the opposite sites. This process may follow a mechanism different from electrostatic interaction.

Figure 9

CVs of 5 mM DCF with (a) pH 3–5, (b) pH 6–9 in 0.2 M BRB, (c) $I_{p}$ vs. pH, and (d) $E_{p}$ vs. pH.

(b)

(c)

(d)

When pH is greater than 5, the peak potential decreases, suggesting the involvement of protons in the oxidation reaction (Figure 9(d)). The peak potential in the DCF oxidation on the ZC-GCE decreases linearly with the pH of the buffer solution according to the following equation: $E_{pa} (V) = - 0.0514 \times pH + 0.9409 (r^{2} = 0.9988)$ . The slope of the equation is close to the Nernstian value (−0.0592 mV) for the electrochemical processes involving an equal number of protons and electrons.

(2) Effect of Scan Rate. The scan rate of CVs is chosen from 0.1 to 0.5 mV·s^–1. In this range, the anodic peak current increases (Figure 10(a)). The highly linear relationship between $I_{p}$ and the scan rate manifests that the electrode process is predominantly controlled by adsorption [29] (Figure 10(b)). The scan rate effect is also examined from the function $I_{p} = f (v^{1 / 2})$ plot. A straight line passing the origin suggests an adsorption-controlled electrode process [30]. This relationship in our study is $I_{p} = (0.003 \pm 0.011) + (0.028 \pm 0.006) \times v^{1 / 2}; r = 0.927$ . With the 95% confident interval, the intercept passes 0 (between –0.008 and 0.014) and confirms an adsorption-controlled process again.

Figure 10

CVs of 5 mM DCF at various scan rates in 0.2 M BRS pH 6.5 on ZIF-67/g-C₃N₄ (a), the plot of $I_{p}$ vs. $v^{1 / 2}$ (b), and $E_{p}$ vs. lnv (c).

(b)

(c)

The relationship between the peak potential and the natural logarithm of the scan rate can provide the number of electrons transferred ( $n$ ) on the electrode surface. For an irreversible system, this relationship is described by Laviron’s equation [31]: $\begin{matrix} (1) & E_{p} = E^{0} - \frac{R \times T}{(1 - α) \times n \times F} \times \ln \frac{R \times T \times K_{s}}{(1 - α) \times n \times F} + \frac{R \times T}{(1 - α) \times n \times F} \times \ln v, \end{matrix}$ where $α$ is the electron-transfer coefficient, $K_{s}$ is the apparent charge-transfer rate constant, $n$ is the number of electrons transferred, $v$ is the scan rate (V·s^–1), $R = 8.314 J \cdot mo l^{- 1} \cdot K^{- 1}$ , and $F = 96500 C \cdot mo l^{- 1} at 298 K$ . The linear regression of $E_{p}$ versus ln(v) is as follows: $\begin{matrix} (2) & E_{p} = (0.751 \pm 0.002) + (0.025 \pm 0.001) \times \ln v; r = 0.991 . \end{matrix}$

The value of $(1 - α) \times n$ calculated from the slope of this straight line is 0.95. For an irreversible system, $α$ is considered as 0.5 [32]; therefore, the value of $n$ is equal to 1.9 (≈2). Considering the pH effect on the anodic peak current, we can conclude that the redox reaction on the modified electrode involves the transfer of two electrons and two protons.

These results are consistent with those reported by Madsen et al. [33] and Goyal et al. [34], in which DCF is oxidized to 5-hydrodiclofenac via losing two electrons and two protons, as shown in Scheme 1.

Scheme 1

Oxidation mechanism of DCF on ZC-GCE.

The enhancement of electrochemical signals could result from the synergic effect of ZIF-67 and g-C₃N₄. The open Co(II) sites, as a Lewis acid [35], could attract the carboxyl group in DCF, and as a Lewis base via acid-base interaction, the graphitic rings in g-C₃N₄ could attract the benzene rings in DCF via π–π interaction. These arguments are schematically illustrated in Scheme 2.

Scheme 2

Schematic illustration of the formation of ZIF-67/g-C₃N₄ modified GCE and its oxidation of DCF.

3.2.2. Linear Range, Detection Limit, Repeatability, and Interference

(1) Linear Range and Detection Limit. The relationship between the peak current and DCF concentration is studied by using differential pulse voltammetry (DPV). In this case, the peak current increases linearly with the concentration of DCF, from 0.2 to 2.2 μM (Figure 11). The regression equation is $I_{p} = (0.941 \pm 0.02) + (3.889 \pm 0.03) \times C; r = 0.999$ . The LOD (3S/n) is 0.071 μM. The detection limit, the linear range, and the sensitivity of the proposed DPV method are compared with previously reported values for the determination of DCF (Table 2). Although the proposed electrode has a relatively narrow linear range, it has high sensitivity and a lower detection limit. This method can be used to determine DCF in pharmaceuticals and water samples in the micromole range.

Figure 11

DPV curves of DCF with different concentrations (0.2–2.2 μM) in 0.2 M BRS pH 6.5 at the modified electrode (a). The plot of $I_{p}$ vs. concentration (b).

(b)

Table 2

Comparison of the analytical performance of the different modified electrodes for the determination of DCF.

Electrodes	Technique	Linear range (μM)	LOD (μM)	References
Gold nanoparticle/multiwalled carbon nanotube modified glassy carbon electrode	SWV	0.03–200	0.02	[9]
Cu-doped zeolite-expanded graphite-epoxy electrode	DPV	0.3–20	0.05	[36]
APTES-amino-AT-silica/GCE	SWV	0.3–20	0.053	[37]
Gold nanoparticles decorated multiwalled carbon nanotubes/graphene oxide/AuE	DPV	0.4–80	0.09	[38]
Ionic liquid modified carbon nanotube paste electrode	DPV	0.5–300	0.2	[7]
Amino-AT/GCE	SWV	0.3–20	0.204	[37]
Au-Pt bimetallic nanoparticles decorated multiwalled carbon nanotubes/gold electrode	DPV	0.5–1000	0.3	[39]
ZIF-67/g-C₃N₄	DPV	0.2–2.2	0.071	The present work

Square wave voltammetry: SWV.

(2) Reproducibility and Repeatability. The reproducibility is studied from four replicates measurements of DCF determination. To investigate the repeatability of this modified electrode, we conduct the measurements ten times with the sample electrode. Figure 12(a) shows very similar DPV curves of four scans on the same working electrode. The small RSD of 1.32% indicates good reproducibility of the proposed method. Figure 12(b) presents the values of peak currents measured on 10 distinct working electrodes under the same modified electrode procedure. The RSD varies from 0.151% to 5.315% in run 1 to run 10, manifesting excellent repeatability.

Figure 12

The DPV of four replicates measurement (a) and the values of peak current of DCF on ZC-GCE modified using (5 μL ZC (1 mg/mL) for ten times on the same electrode (b).

(b)

The biological sample is a very complex mixture consisting of various ions and molecules. Possible interfering electroactive species on the biological samples include inorganic salts (KHCO₃, Na₂SO₄, CaCl₂, and NH₄NO₃) and organic compounds (uric acid, caffeine, paracetamol, and ascorbic acid). Table 3 reveals that inorganic salts do not significantly interfere with the measurement even at extremely high content (100–320 fold). Ascorbic acid does not seem to affect the peak current at 480-fold concentration. Paracetamol, uric acid, and caffeine exert a medium effect on the peak current at a concentration of 40 to 80-fold higher than that of DCF. These results confirm the relevant selectivity of the proposed method for DCF detection.

Table 3

Effect of some foreign substances on the determination of 1 μM DFC in 0.2 M BRBS pH 6.5.

Interferents	Tolerance level (M/M)	Rev. (%)
KHCO₃	320	6.80
Na₂SO₄	480	13.57
CaCl₂	320	12.86
NH₄NO₃	80	6.58
Uric acid	80	6.34
Caffeine	80	10.14
Paracetamol	40	5.13
Ascorbic acid	480	9.38

3.2.3. Real Sample Analysis

This DPV method is used to analyze five actual human urine samples. To determine the method’s accuracy, we spike each sample with 50 μM of DCF, and the relative recovery (Rev.) is calculated. All the values fall in the expectable range of 95.4–105% (Table 4). The content of DCF in the samples is also determined with the HPLC method for comparison. When $α = 0.05$ , the paired samples $t$ -test proves that there is no statistically significant difference between the two methods ( $p_{two - tailed} = 0.388 (> 0.05)$ ; $t (4) = 0.968$ ). These results demonstrate a good performance of the presented method for the determination of DCF in urine samples.

Table 4

The results of DCF analysis in urine by the proposed DPV method and HPLC.

Sample	DPV analysis			Rev (%)	HPLC analysis
Sample	Original content (μM)	Spiked (μM)	Found (μM)	Rev (%)	Original content (μM)	Found (μM)
Urine 1	—	50	$51.243 \pm 0.229$	102.49	—	$48.931 \pm 0.015$
Urine 2	—	50	$48.102 \pm 0.085$	96.20	—	$47.823 \pm 0.204$
Urine 3	—	50	$49.215 \pm 0.081$	98.43	—	$50.387 \pm 0.139$
Urine 4	0.257 ± 0.074	50	$54.013 \pm 0.167$	104.96	$0.261 \pm 0.009$	$52.715 \pm 0.077$
Urine 5	—	50	$47.692 \pm 0.073$	95.38	—	$47.570 \pm 0.008$

(–): not found.

4. Conclusion

In this research, we successfully synthesized ZIF-67/g-C₃N₄ with the self-assembly method and used the material to modify a glassy carbon electrode for the electrocatalytic determination of diclofenac. The g-C₃N₄ is highly dispersed in ZIF-67 through an ultrasonic assisted stir to form a composite of g-C₃N₄ and ZIF-67. The enhancement of electrochemical signals is due to the synergic effect of ZIF-67 and g-C₃N₄. The oxidation of diclofenac on the modified electrode takes place with a two-electron-proton mechanism. The electrode process is controlled by adsorption. The proposed DPV method exhibits high sensitivity with a low detection limit and can be used to determine diclofenac at trace levels.

Footnotes

Data Availability

The data used to support the findings of this study are available from the corresponding author upon request.

Conflicts of Interest

The authors declare that they have no conflicts of interest.

Acknowledgments

This work was supported by the Hue University under the Core Research Program No. NCM.DHH.2019.08.

References

Arancibia

J. A.

Escandar

G. M.

Complexation study of diclofenac with β-cyclodextrin and spectrofluorimetric determination

Analyst 1999 124

7896286

12 1833 1838

10.1039/a906719a

2-s2.0-0033381267

10746311

Cleuvers

Mixture toxicity of the anti-inflammatory drugs diclofenac, ibuprofen, naproxen, and acetylsalicylic acid

Ecotoxicology and Environmental Safety 2004 59

7896286

3 309 315

10.1016/S0147-6513(03)00141-6

2-s2.0-1642393941

15388270

Jin

Zhang

Determination of diclofenac sodium by capillary zone electrophoresis with electrochemical detection

Journal of Chromatography. A 2000 868

7896286

1 101 107

10.1016/S0021-9673(99)01149-8

2-s2.0-0033972853

Alquadeib

B. T.

Development and validation of a new HPLC analytical method for the determination of diclofenac in tablets

Saudi pharmaceutical journal 2019 27

7896286

1 66 70

10.1016/j.jsps.2018.07.020

2-s2.0-85051650782

30662308

Arcelloni

Lanzi

Pedercini

Molteni

Fermo

Pontiroli

Paroni

High-performance liquid chromatographic determination of diclofenac in human plasma after solid-phase extraction

Journal of Chromatography. B, Biomedical Sciences and Applications 2001 763

7896286

1–2 195 200

10.1016/S0378-4347(01)00383-8

2-s2.0-0035813550

11710578

Arancibia

J. A.

Boldrini

M. A.

Escandar

G. M.

Spectrofluorimetric determination of diclofenac in the presence of α-cyclodextrin

Talanta 2000 52

7896286

2 261 268

10.1016/S0039-9140(00)00338-6

2-s2.0-0034697837

18967984

Ensafi

A. A.

Izadi

Karimi-Maleh

Sensitive voltammetric determination of diclofenac using room-temperature ionic liquid-modified carbon nanotubes paste electrode

Ionics 2013 19

7896286

1 137 144

10.1007/s11581-012-0705-0

2-s2.0-84871938940

Sasal

Tyszczuk-Rotko

Wójciak

Sowa

First electrochemical sensor (screen-printed carbon electrode modified with carboxyl functionalized multiwalled carbon nanotubes) for ultratrace determination of diclofenac

Materials 2020 13

7896286

3 781

10.3390/ma13030781

32046335

Afkhami

Bahiraei

Madrakian

Gold nanoparticle/multi-walled carbon nanotube modified glassy carbon electrode as a sensitive voltammetric sensor for the determination of diclofenac sodium

Materials Science and Engineering: C 2016 59

7896286

168 176

10.1016/j.msec.2015.09.097

2-s2.0-84943798736

26652361

10.

Qian

Sun

Qin

Hydrothermal synthesis of zeolitic imidazolate framework-67 (ZIF-67) nanocrystals

Materials Letters 2012 82

7896286

2012 220 223

10.1016/j.matlet.2012.05.077

2-s2.0-84863104726

11.

Yang

Ren

S. S.

Zhao

Hang

Chen

Zheng

Selective separation of methyl orange from water using magnetic ZIF-67 composites

Chemical Engineering Journal 2018 333

7896286

49 57

10.1016/j.cej.2017.09.099

2-s2.0-85033476475

12.

Jin

Zhao

Performance of ZIF-67 - Derived fold polyhedrons for enhanced photocatalytic hydrogen evolution

Chemical Engineering Journal 2020 382

7896286

123051

10.1016/j.cej.2019.123051

2-s2.0-85073165798

13.

Liu

Zong

Yang

Ren

Shi

Wang

Jiang

Nanoporous ZIF-67 embedded polymers of intrinsic microporosity membranes with enhanced gas separation performance

Journal of Membrane Science 2018 548

7896286

309 318

10.1016/j.memsci.2017.11.038

2-s2.0-85034862022

14.

Sohouli

Karimi

M. S.

Khosrowshahi

E. M.

Rahimi-Nasrabadi

Ahmadi

Fabrication of an electrochemical mesalazine sensor based on ZIF-67

Measurement 2020 165

7896286

108140

10.1016/j.measurement.2020.108140

15.

Wang

Maeda

Thomas

Takanabe

Xin

Carlsson

J. M.

Domen

Antonietti

A metal-free polymeric photocatalyst for hydrogen production from water under visible light

Nature Materials 2009 8

7896286

1 76 80

10.1038/nmat2317

2-s2.0-57849130247

18997776

16.

Shen

Hong

Lin

Gao

Chen

A facile approach to synthesize novel oxygen-doped g-C 3 N 4 with superior visible-light photoreactivity

Chemical Communications 2012 48

7896286

98 12017 12019

17.

Zhang

Thomas

Antonietti

Wang

Activation of carbon nitride solids by protonation: morphology changes, enhanced ionic conductivity, and photoconduction experiments

Journal of the American Chemical Society 2009 131

7896286

1 50 51

18.

Chen

Zhang

Liu

Alharbi

N. S.

Rabah

S. O.

Wang

Synthesis and fabrication of g-C₃N₄-based materials and their application in elimination of pollutants

Science of The Total Environment 2020 731, article 139054

7896286

10.1016/j.scitotenv.2020.139054

19.

Yan

S. C.

Z. S.

Zou

Z. G.

Photodegradation performance of g-C3N4 fabricated by directly heating melamine

Langmuir 2009 25

7896286

17 10397 10401

10.1021/la900923z

2-s2.0-69949171130

20.

Thomas

Fischer

Goettmann

Antonietti

Müller

J. O.

Schlögl

Carlsson

J. M.

Graphitic carbon nitride materials: variation of structure and morphology and their use as metal-free catalysts

Journal of Materials Chemistry 2008 18

7896286

41 4893 4908

10.1039/b800274f

2-s2.0-54049153179

21.

Bojdys

M. J.

Müller

Antonietti

Thomas

Ionothermal synthesis of crystalline, condensed, graphitic carbon nitride

Chemistry - A European Journal 2008 14

7896286

27 8177 8182

10.1002/chem.200800190

2-s2.0-53849099698

22.

Bai

Wang

Yao

Zhu

Enhanced oxidation ability of g-C3N4 photocatalyst via C60 modification

Applied Catalysis B: Environmental 2014 152

7896286

262 270

23.

Tonda

Kumar

Kandula

Shanker

Fe-doped and -mediated graphitic carbon nitride nanosheets for enhanced photocatalytic performance under natural sunlight

Journal of Materials Chemistry A 2014 2

7896286

19 6772 6780

10.1039/c3ta15358d

2-s2.0-84898842140

24.

Long

Lin

Wang

Thermally-induced desulfurization and conversion of guanidine thiocyanate into graphitic carbon nitride catalysts for hydrogen photosynthesis

Journal of Materials Chemistry A 2014 2

7896286

9 2942 2951

10.1039/c3ta14339b

2-s2.0-84893494843

25.

Lin

K.-Y. A.

Lee

W.-D.

Self-assembled magnetic graphene supported ZIF-67 as a recoverable and efficient adsorbent for benzotriazole

Chemical Engineering Journal 2016 284

7896286

1017 1027

26.

Awadallah-F

Hillman

Al-Muhtaseb

S. A.

Jeong

H.-K.

On the nanogate-opening pressures of copper-doped zeolitic imidazolate framework ZIF-8 for the adsorption of propane, propylene, isobutane, and n-butane

Journal of Materials Science 2019 54

7896286

7 5513 5527

10.1007/s10853-018-03249-y

2-s2.0-85058943096

27.

Jiao

Han

Rong

Fang

Liu

Han

Characterization of pine-sawdust pyrolytic char activated by phosphoric acid through microwave irradiation and adsorption property toward CDNB in batch mode

Desalination and Water Treatment 2017 77

7896286

247 255

10.5004/dwt.2017.20780

2-s2.0-85026246592

28.

Adeyeye

C. M.

P.-K.

Diclofenac sodium

Analytical profiles of drug substances 1990 19

7896286

Elsevier

123 144

29.

Bard

A. J.

Faulkner

L. R.

Fundamentals and applications

Electrochemical methods 2001 2

7896286

482 580 632

30.

Soleymani

Hasanzadeh

Shadjou

Khoubnasab Jafari

Gharamaleki

J. V.

Yadollahi

Jouyban

A new kinetic-mechanistic approach to elucidate electrooxidation of doxorubicin hydrochloride in unprocessed human fluids using magnetic graphene based nanocomposite modified glassy carbon electrode

Materials Science and Engineering: C 2016 61

7896286

638 650

10.1016/j.msec.2016.01.003

2-s2.0-84953791181

26838892

31.

Laviron

General expression of the linear potential sweep voltammogram in the case of diffusionless electrochemical systems

Journal of Electroanalytical Chemistry and Interfacial Electrochemistry 1979 101

7896286

1 19 28

10.1016/S0022-0728(79)80075-3

2-s2.0-49249148639

32.

Electrochemical determination of dipyridamole at a carbon paste electrode using cetyltrimethyl ammonium bromide as enhancing element

Colloids Surfaces B Biointerfaces 2007 55

7896286

1 77 83

10.1016/j.colsurfb.2006.11.009

2-s2.0-33846799332

17178451

33.

Madsen

K. G.

Skonberg

Jurva

Cornett

Hansen

S. H.

Johansen

T. N.

Olsen

Bioactivation of diclofenac in vitro and in vivo: correlation to electrochemical studies

Chemical Research in Toxicology 2008 21

7896286

5 1107 1119

10.1021/tx700419d

2-s2.0-47549117734

18419141

34.

Goyal

R. N.

Chatterjee

Agrawal

Electrochemical investigations of diclofenac at edge plane pyrolytic graphite electrode and its determination in human urine

Sensors and Actuators B: Chemical 2010 145

7896286

2 743 748

10.1016/j.snb.2010.01.038

2-s2.0-77949303968

35.

X. D.

Wang

C. C.

Liu

J. G.

Zhao

X. D.

Zhong

Y. X.

Wang

Extensive and selective adsorption of ZIF-67 towards organic dyes: performance and mechanism

Journal of Colloid and Interface Science 2017 506

7896286

437 441

10.1016/j.jcis.2017.07.073

2-s2.0-85025641348

28753488

36.

Manea

Ihos

Remes

Burtica

Schoonman

Electrochemical determination of diclofenac sodium in aqueous solution on cu-doped zeolite-expanded graphite-epoxy electrode

Electroanalysis 2010 22

7896286

17-18 2058 2063

10.1002/elan.201000074

2-s2.0-77956639876

37.

Jiokeng

S. L. Z.

Tonle

I. K.

Walcarius

Amino-attapulgite/mesoporous silica composite films generated by electro- assisted self-assembly for the voltammetric determination of diclofenac

Sensors and Actuators B: Chemical 2019 287

7896286

296 305

10.1016/j.snb.2019.02.038

2-s2.0-85061795446

38.

Nasiri

Rounaghi

G. H.

Ashraf

Deiminiat

A new electrochemical sensing platform for quantitative determination of diclofenac based on gold nanoparticles decorated multiwalled carbon nanotubes/graphene oxide nanocomposite film

International Journal of Environmental Analytical Chemistry 2021 101

7896286

2 153 166

10.1080/03067319.2019.1661396

2-s2.0-85072015651

39.

Eteya

M. M.

Rounaghi

G. H.

Deiminiat

Fabrication of a new electrochemical sensor based on AuPt bimetallic nanoparticles decorated multi-walled carbon nanotubes for determination of diclofenac

Microchemical Journal 2019 144

7896286

254 260

10.1016/j.microc.2018.09.009

2-s2.0-85053760568

Electrochemical Determination of Diclofenac by Using ZIF-67/ g- C 3 N 4 Modified Electrode

Abstract

1. Introduction

2. Experimental

2.1. Materials

2.2. Material Synthesis

2.3. Instruments

2.4. Preparation of Electrode and Actual Sample

2.4.1. Electrode Preparation

2.4.2. Real Samples

3. Results and Discussion

3.1. Characterization of Materials

3.2. Electrochemical Determination of Diclofenac by Using (5/5)ZIF-67/g-C3N4

3.2.1. The Cyclic Voltammetry of DCF on (5/5)ZIF-67/g-C3N4 Modified Electrode (ZC-GCE)

3.2.2. Linear Range, Detection Limit, Repeatability, and Interference

3.2.3. Real Sample Analysis

4. Conclusion

Footnotes

Data Availability

Conflicts of Interest

Acknowledgments

References

3.2. Electrochemical Determination of Diclofenac by Using (5/5)ZIF-67/g-C₃N₄

3.2.1. The Cyclic Voltammetry of DCF on (5/5)ZIF-67/g-C₃N₄ Modified Electrode (ZC-GCE)