Electroanalytical Sensing of Ivermectin Using a Carbon-Black-Modified Glassy-Carbon Electrode

Abstract

During the severe acute respiratory syndrome coronavirus (SARS-CoV-2) pandemic, ivermectin (IVM), a broad-spectrum antiparasitic drug, was one of the medications prescribed to manage symptoms. However, its effectiveness against the virus has not been conclusively demonstrated. The increased consumption of IVM raised environmental and health concerns, including bioaccumulation and microbial resistance. To address these issues, electroanalytical methods have been explored for IVM detection, offering advantages such as low cost, portability, and high sensitivity. Super-P carbon black (SPCB) is a conductive nanomaterial used to modify glassy carbon electrodes, enhancing electrochemical performance. In this work, electrochemical sensors based on SPCB were developed using the drop-casting technique for IVM sensing. Through studies using cyclic voltammetry (CV), it was determined that the mass transport for the glassy carbon electrode modified with Super-P carbon black (SPCB/GCE) is governed by the adsorption of the species. After parameter optimization for differential pulse voltammetry technique, the sensor exhibited a linear working range of 10-100 µmol L^-1, a limit of detection (LOD) of 1.3 µmol L^-1, a limit of quantification (LOQ) of 4.2 µmol L^-1, and a sensitivity of 0.101 µA µmol L^-1. The developed method was applied to analysis of pharmaceutical tablets, tap water, and synthetic urine.

Keywords:
carbon nanoparticles; electrochemical sensors; differential pulse voltammetry; COVID-19; ivermectin

Introduction

Ivermectin (IVM) is an antiparasitic drug belonging to the class of macrocyclic lactones. It is used to treat infections caused by arthropods and nematodes that affect humans, domestic animals, and livestock. In addition to its widespread use in treating conditions such as mites, roundworms, and parasites, particularly in the livestock sector, IVM gained attention in 2020 during the pandemic as a potential treatment for severe acute respiratory syndrome coronavirus (SARS-CoV-2). However, its effectiveness against the virus has not been scientifically proven.¹ During this period, the consumption of IVM increased significantly, raising concerns among health authorities due to its toxicity to humans and its potential as an emerging contaminant in terrestrial and aquatic environments. This raises issues such as bioaccumulation, microbial resistance, and chronic toxicity in organisms.²

Despite its extensive use in veterinary and human medicine, there is currently no specific legislation establishing limits for ivermectin in water or wastewater. However, it is classified as a contaminant of emerging concern due to its high persistence in sediments and extreme toxicity to aquatic invertebrates. For instance, lethal effects on organisms such as Daphnia magna are observed at concentrations in the low ng L^-1 range. Consequently, the lack of regulation does not imply a lack of risk, but rather underscores the urgent need for accessible and sensitive analytical methodologies to monitor this compound and support the creation of future environmental guidelines.³,⁴

Given the negative environmental and health impacts associated with its indiscriminate use, various techniques have been explored for IVM detection, including chromatography coupled with mass spectrometry,⁵-⁸ capillary electrophoresis-UV,⁹ and optical immunobiosensors.¹⁰ However, these methods have limitations, such as high equipment costs, the need for specialized operators, and the generation of large volumes of waste with regard to chromatography methods. In this context, electroanalytical techniques emerge as a viable alternative, offering portable equipment, low-cost materials, and high sensitivity for the detection of target analytes.¹¹

Electroanalytical methods stand out for their advantages over traditional techniques, making them suitable for the detection of IVM under various analytical conditions. In the literature, certain electrodes, such as boron-doped diamond (BDD)¹² and laser-induced graphene (LIG),¹³ are used to determine IVM, indicating a good detection and quantification range. However, known limitations, such as the elevated cost of BDD and the limited sensitivity of unmodified LIG electrodes, pose significant challenges for electroanalytical methods. Thus, some studies have highlighted modifications that enhance the sensitivity of the analytical signal, allowing the development of more advanced methods with a wide range of materials. Some reported sensors include a reduced graphene oxide decorated with silver nanoparticles doped with B and S heteroatoms,¹ β-cyclodextrin/graphene,¹⁴ and glutaraldehyde¹⁵ as modifiers. The exploration of accessible and low-cost materials is crucial for the electroanalytical detection and quantification of IVM.

There are three main categories of commercially produced carbon black materials, such as furnace black, acetylene black, and thermal black. Super-P carbon black (SPCB) belongs to the furnace black category, and it is produced through the partial combustion of hydrocarbons, including petroleum derivatives. It exhibits characteristics like high electrical and thermal conductivity and lubrication. Due to these properties, SPCB is used in various applications, including rubber reinforcement, printing inks, and electrochemical energy storage systems like batteries.¹⁶ SPCB is a conductive nanomaterial known for its low cost and is considered a recyclable material option for developing electrochemical devices aimed at detecting various analytes. It is comparable to well-known carbon nanomaterials like graphene, carbon nanotubes, carbon aerogel, carbon xerogel, and fullerenes in terms of electrical conductivity and porosity.¹⁷-²² Some studies have reported the use of SPCB for the detection of analytes such as azithromycin,²³ hydrochlorothiazide,²⁴ and nimesulide.²⁵

In this study, a sensitive and cost-effective electrochemical sensor was developed for the detection of IVM in different samples. The sensor fabrication involved modifying a glassy carbon electrode via a drop-casting technique, employing a simple suspension of Super-P carbon black (SPCB) in dimethylformamide (DMF). This approach takes advantage of the conductive properties and surface area of carbon black to enhance sensor performance, providing a robust platform for efficient and selective IVM detection.

Experimental

Reagents and solutions

All reagents used in this work were of analytical grade and used as received. The stock solution of IVM (10 mmol L^-1) (Sigma-Aldrich, USA) was prepared in ethanol (Sciavicco, Brazil), and before the experiments, it was diluted in an appropriate supporting electrolyte. The aqueous solutions were prepared with high-purity deionized water with the resistivity of at least 18 mΩ cm, obtained from a Millipore Direct 8 water purification system (Millipore, Germany). A 0.1 mol L^-1 phosphate buffer (PB) solution was prepared using monosodium phosphate, and disodium phosphate (Sigma-Aldrich, USA) and a 0.1 mol L^-1 sulfuric acid solution (Vetec, Brazil) were used as supporting electrolytes. All electrolytic solutions containing IVM were prepared in the presence of 30% ethanol (v/v) to avoid any IVM precipitate due to its low solubility in water. The pH-values of the PB solutions (2.0, 7.0 and 12.0) were adjusted with sodium hydroxide solution (3.0 mol L^-1).

Preparation of the modified electrode

For the preparation of the modifier (Figure 1), a suspension of SPCB in DMF was used at a ratio of 1.0 mL of DMF per 1.0 mg of SPCB. This suspension was prepared in a 2.0 mL vial and then subjected to ultrasonic bath treatment for 2 h to ensure homogenization. Before each modification, the 3 mm diameter glassy carbon electrode (GCE) was carefully cleaned and manually polished with alumina slurry (0.05 µm) followed by rinsing thoroughly with deionized water. For the electrode modification, an aliquot of 5.0 µL of the suspension was applied to the surface of the GCE. The electrode was then dried using a 2000 W heat gun (Vonder^®, Brazil) at 50 °C for approximately 8 min. After the modification, the GCE was called SPCB/GCE.

Figure 1
Schematic presentation of the electrode preparation process and electrochemical analysis system. (a) preparation of the modifying mixture based on Super P carbon black; (b) ultrasonic bath for homogenization of the mixture; (c) modification of the GCE surface by drop casting with the modifier; (d) drying with heat gun Vonder^®; (e) electrochemical detection by DPV.

Electrochemical measurements

Cyclic voltammetry (CV) and differential-pulse voltammetry (DPV) measurements were performed with a portable potentiostat Ivium CompactStat.h (IviumTechnologies, Netherlands), connected to a computer with an IviumSoft software (version 2.783). The electrochemical experiments were carried out in a cylindrical shape electrochemical cell (internal volume ca. 50 mL) using a Pt wire as the counter electrode, a miniaturized reference electrode (Ag|AgCl|KCl_{(3 mol L}-1₎) and an SPCB/GCE as the working electrode.

Sample preparation

The determination of IVM was performed by DPV, with 0.1 mol L^-1 H₂SO₄ as the supporting electrolyte. The proposed method was applicated using addition/recovery experiments in tap water and synthetic urine samples. For tap water analysis, two samples were tested: sample A, collected from Paço do Lumiar (Maranhão, Brazil), and sample B, collected from São Luís (Maranhão, Brazil). The procedure involved diluting the sample at a 1:10 (v/v) ratio in the supporting electrolyte (0.1 mol L^-1 H₂SO₄) and spiking the samples A and B with 10 and 20 µmol L^-1 of IVM, respectively. The synthetic urine sample was obtained according to the procedure described by Laube e al.,²⁶ dissolving 0.73 g of NaCl, 0.40 g of KCl, 0.28 g of CaCl₂·2H₂O, 0.56 g of Na₂SO₄, 0.35 g of KH₂PO₄, 0.25 g of NH₄Cl, and 6.25 g of urea in deionized water in a 250 mL volumetric flask. This sample was diluted at a 1:10 (v/v) ratio using the supporting electrolyte (0.1 mol L^-1 H₂SO₄) and was spiked with 20 µmol L^-1 of IVM. For pharmaceutical analysis, a formulation containing 6.0 mg of IVM per capsule was purchased from a local pharmacy in São Luís. Ten capsules were finely ground using a mortar, followed by weighing out approximately 22.0 mg of the resulting powder and diluting to 10.0 mL with ethanol in a volumetric flask.

Results and Discussion

As characterized in a previous work²⁷ by scanning electron microscopy (SEM), carbon black aggregates exhibit an amorphous, porous, and rough surface. The interfacial properties of the electrodes were evaluated using electrochemical impedance spectroscopy (EIS) in another work.²⁴ The Nyquist plot obtained for the GCE showed a characteristic profile, consisting of a highfrequency semicircle, attributed to the charge-transfer process, and a low-frequency linear region, indicative of a diffusion-limited process. Analogously, the modified electrode (SPCB/GCE) also exhibited a profile with a semicircle and a linear portion. However, the diameter of the semicircular arc for the SPCB/GCE was notably smaller, which denotes a significant reduction in the charge-transfer resistance (Rct). The quantified Rct values were 1125 Ω for the GCE and 14 Ω for the SPCB/GCE, confirming the superior performance of the modified electrode.

Electrochemical behavior of IVM

The first step of this study was to evaluate the electrochemical behavior of IVM on the SPCB/GCE and on the bare GCE using the cyclic voltammetry technique, as shown in Figure 2. The cyclic voltammograms were recorded in H₂SO₄ solution (0.1 mol L^-1, 30% ethanol, v/v) in the absence and presence of 100 µmol L^-1 IVM. It was observed that, in the absence of IVM, no voltammetric peaks were present, indicating that the electrode surface was clean and free from electroactive impurities. In contrast, in the presence of 100 µmol L^-1 IVM, two anodic peaks were detected at approximately +1.37 V (peak I) and +1.48 V (peak II) vs. Ag|AgCl|KCl (3 mol L^-1), with no reduction peaks within the applied potential range (0.0 to +1.6 V), suggesting that the oxidation process of IVM is irreversible. The presence of a second oxidation peak suggests a complex reaction mechanism. This additional signal could arise from the further oxidation of the functional groups of the molecule or from the electrochemical activity of reaction byproducts formed at the electrode surface.

Figure 2
Cyclic voltammograms recorded in 0.1 mol L^-1 H₂SO₄ solution (30% ethanol, v/v) in the absence (modified (black solid line) and unmodified (black dash line)) and presence (modified (blue line) and unmodified (red line)) of 100 µmol L^-1 IVM. Instrumental conditions: scan rate = 50 mV s^-1 and step potential = 5 mV.

Additionally, the current obtained with the unmodified electrode was 1.65 µA for the first peak and 1.08 µA for the second peak. In comparison, the modified electrode exhibited a current of 5.05 µA for the first peak and 2.56 µA for the second peak, approximately 3 times higher for the first peak and 2 times higher for the second peak compared to the unmodified electrode. The results (Figure 2) confirmed that the modification with SPCB significantly enhanced the analyte signal, indicating that the SPCB/GCE electrode provided good sensitivity for IVM detection. The increased surface area due to the presence of SPCB on the electrode surface was assessed in a study of the doublelayer capacitance as a function of the scan rate (Figure S1, Supplementary Information (SI) section), using the GCE and SPCB/GCE electrodes. This revealed that the electrode surface area increased by approximately two-fold for the modified electrode, compared to the plain GCE.

The influence of the pH of the medium was studied, but during the measurements, there was no clear response for ivermectin oxidation. Consequently, the effect was evaluated in four different conditions: alkaline (pH 12.0), neutral (pH 7.0), acidic (pH 2.0), and sulfuric acid (H₂SO₄, pH 1.75) The cyclic voltammograms recorded at pH 12.0 and 7.0, Figures S2a and S2b, respectively, the signal exhibited poor definition, while at pH 2 (Figure S2c), a more defined signal was observed near a potential of +1.39 V, indicating that an acidic medium is more favorable for the oxidation of IVM. When compared to a more acidic solution, specifically 0.1 mol L^-1 H₂SO₄ (Figure S2d), an improvement in signal definition and peak intensity of the analyte was observed. Therefore, the 0.1 mol L^-1 H₂SO₄ solution was selected as the electrolyte for subsequent studies, this result is supported with literature reports, which indicate that ivermectin exhibits greater stability in acidic environments.¹²

To evaluate the effect of electrode surface poisoning by IVM oxidation byproducts, a study was performed with consecutive CV measurements (n = 12) on GCE and SPCB/GCE. In Figure S3a it is possible to observe the unstable behavior of the GCE in sequential IVM measurements, dropping below the signal in the absence of ivermectin. In contrast, Figure S3b demonstrates that the SPCB/GCE minimizes this effect during repeated scans. Additionally, this behavior indicates that the proposed modification serves to attenuate the poisoning effect caused by IVM redox products on the GCE surface, enhancing the repeatability and stability of the measurements.

The process of electron transfer between IVM species at the proposed electrode was performed using 0.1 mol L^-1 H₂SO₄ (30% ethanol) solution containing of 100 μmol L^-1 IVM in the scan rate range from 10 to 90 mV s^-1, see Figure 3a. The linear relationship between the peak current and the scan rate (Figure 3b) and the linear relationship between the peak current and the square root of the scan rate (Figure 3c) showed linearities of 0.995 and 0.983, respectively, indicating that the electron transfer process may occur through adsorption. One way to verify this result is by analyzing the dependence between the logarithm of the peak current and the logarithm of the scan rate (Figure 3d), which yielded the equation log Ip = 0.870 log ν + 1.038, where Ip is peak current and ν is scan rate. In this study, angular coefficients close to 0.5 or 1.0 indicate predominant charge transfer control by diffusion or adsorption, respectively, implying that the electron transfer process of IVM at the proposed electrode occurs through adsorption.

Figure 3
(a) Cyclic voltammograms recorded using 100 μmol L^-1 IVM in 0.1 mol L^-1 H₂SO₄ (30% ethanol), (b) peak current (Ip) vs. scan rate, (c) peak current (Ip) vs. square root of scan rate, and (d) logarithm of peak current vs. logarithm of scan rate, for the SPCB/GCE. Instrumental conditions: scan rate from 10 to 90 mV s^-1 and step potential of 5 mV s^-1.

The linear relationship between peak potential (Ep) and natural logarithm of scan rate (ln v) was studied and illustrated in Figure S4 (SI section), the equation Ep = 1.304 + 0.020ln (v) was obtained. Using the angular coefficient from this equation, along with equation 1 and the calculated α from Ep - Ep/2 = 47.7/(1 - α), where Ep/2 is half-peak potential and α is the electron transfer coefficient which is equal to 0.29, it was possible to determine the number of electrons involved in the process, resulting in a value of 2 electrons, approximately.²⁸ To date, there are no reports in the literature presenting the calculation of the number of electrons for this process, which precludes a direct comparison. Consequently, a definitive reaction mechanism could not be proposed, as the specific protonto-electron ratio involved could not be determined. The construction of an oxidation potential versus pH curve was not possible due to the lack of a well-defined response for ivermectin in PB at pH values above 2.0. Furthermore, the voltammetric profiles obtained in PB and H₂SO₄ are quite distinct, with the latter exhibiting two oxidation processes.

(1) $${\mathrm{E}}_{\mathrm{p}}={\mathrm{E}}^{\circ }-\left(\frac{\mathrm{RT}}{\alpha \mathrm{nF}}\right)[0.78-\ln \left(\frac{{\mathrm{k}}^{\circ }}{{\mathrm{D}}^{\frac{1}{2}}}\right)+\frac{1}{2}(\ln (\alpha \mathrm{nF})-\ln (\mathrm{RT}))+\frac{1}{2}\ln (\mathrm{v})]$$

where Ep is the peak potential, E° is the formal standard redox potential, R is is the universal gas constant (8,314 J K^-1 mol^-1), T is temperature (298 K), α is the electron transfer coefficient, n is the number of electrons transferred, F is Faraday constant (96485 C mol^-1), k° is the standard heterogeneous electron transfer rate constant, D is the diffusion coefficient, ν is scan rate.

DPV system optimization and analytical performance

Differential pulse voltammetry (DPV) was explored for IVM determination using the SPCB/GCE. The parameters of the DPV technique, such as step (5-10 mV), modulation amplitude (10-100 mV), modulation time (0.01-0.10 s), were evaluated and optimized based on the resulting current and signal definition, which was assessed through the halfpeak width (W¹/₂) (Figure S5, SI section). Table S1 (SI section) describes the optimal DPV analytical parameters for IVM determination using the SPCB/GCE. To the IVM determination using the DPV technique an analytical curve was constructed via the successive additions of IVM solutions.

Figure 4a shows a series of differential-pulse voltammograms obtained for increments of 10 µmol L^-1 IVM in 0.1 mol L^-1 H₂SO₄ (30% v/v ethanol) solution. A linearity was obtained in the concentration range between 10 to 100 µmol L^-1 IVM, as presented in Figure 4b. The linear regression showed the equation Ip (µA) = 0.101 ± 0.002 [IVM] (µmol L^-1) + 0.174 ± 0.124 with an R² value of 0.998. Under these conditions, the limit of detection (LOD) and limit of quantification (LOQ) values were determined using equations 2 and 3.

Figure 4
(a) Baseline-treated DPV recordings for different concentrations of IVM (from 10 to 100 μmol L^-1) and (b) the respective analytical curve. DPV conditions: potential step: 8 mV, modulation amplitude: 100 mV, and modulation time: 0.02 s; supporting electrolyte: 0.1 mol L^-1 H₂SO₄ solution (30% ethanol, v/v).

(2) $$\mathrm{LOD}=\frac{3\mathrm{s}}{\mathrm{b}}$$

(3) $$\mathrm{LOQ}=\frac{10\mathrm{s}}{\mathrm{b}}$$

where s is the standard deviation of the blank and b the slope of the analytical curve.²⁹ The values obtained for the LOD and LOQ were 1.3 and 4.2 μmol L^-1, respectively.

The studies of reproducibility and repeatability of the modification for IVM on the SPCB/GCE surface were conducted using the optimized DPV method. For the reproducibility study, the response of three modifications on the glassy carbon surface was evaluated using a concentration of 50 μmol L^-1. The repeatability study involved seven consecutive measurements at three different concentrations (25, 50, and 75 μmol L^-1). In the reproducibility study (Figure S6, SI section), the measurements between the electrodes showed a relative standard deviation (RSD) of 4.58%, indicating good reproducibility of the electrode modification. In the repeatability study (Figure S7, SI section), the RSD values obtained were 3.65% for 25 μmol L^-1, 2.85% for 50 μmol L^-1, and 2.55% for 75 μmol L^-1. These values demonstrate that the electrode remains stable and exhibits good repeatability.

Sample analysis

The analytical performance of the SPCB/GCE for the determination of IVM in different matrices was evaluated under the same optimized conditions previously established for the quantification of the analyte. To assess the accuracy of the proposed method, two distinct approaches were employed. The first involved recovery experiments using two types of water samples (Figures 5 and 6) and synthetic urine (Figure S7), each spiked with different concentrations of IVM. The second test consisted of the analysis of two pharmaceutical (Figures S8 and S9, SI section) formulations with known IVM mass, where the samples were homogenized and subsequently diluted in the supporting electrolyte. Table 1 presents the added and recovered concentrations, along with the respective recovery percentages for tap water and synthetic urine, as well as the IVM mass determined for the pharmaceutical samples.

Table 1
Results obtained for the determination of IVM in tap water samples by DPV using SPCB/GCE

Sample	Spiked / (μmol L-1)	Found / (μmol L -1)	Recoverya / %
Tap water A	10.0	10.0 ± 0.2	100 ± 2
Tap water B	20.0	20.7 ± 0.9	104 ± 4
Urine	20.0	21.6 ± 0.3	108 ± 1
Sample	IVM labeled value / (mg per tablet)	Proposed method / (mg per tablet)	Test tb
A	6.0	5.8 ± 0.3	1.38
B	6.0	6.1 ± 0.2	1.19

• ^a
  Results presented as average value ± standard deviation (n = 3);
• ^b
  Degrees of freedom: 2 and significance level: 95% (n = 3). IVM: ivermectin.

Figure 5
(a) DPV recordings using the SPCB/GCE for determination of IVM in tap water A and the (b) respective standard addition calibration plot. The concentration levels of IVM: 10 (green line); 20 (blue line), and 30 (purple line) μmol L^-1. DPV conditions in Table S1 ( SI section), supporting electrolyte: 0.1 mol L^-1 H₂SO₄ solution (30% ethanol, v/v).

Figure 6
DPV recordings using the SPCB/GCE for determination of IVM in tap water B and the (b) respective standard addition calibration plot. The concentration levels of IVM: 20 (green line); 40 (blue line), and 60 (purple line) μmol L^-1. DPV conditions in Table S1 ( SI section), supporting electrolyte: 0.1 mol L^-1 H₂SO₄ solution (30% ethanol, v/v).

The recovery values are below 110%, indicating that the SPCB/GCE is capable of accurately quantifying IVM and confirming the absence of matrix effects in the analysis. This study is presented as a proof-of-concept evaluation in simplified aqueous and synthetic biological matrices; therefore, systematic interference studies in complex real samples were considered beyond the scope of this work and may be addressed in future investigations. It is worth highlighting that the analysis of the water samples was performed with minimal sample preparation, requiring only a simple dilution (10-fold). Despite the influence of matrix complexity on recovery values, the results remained within valid analytical limits, demonstrating the suitability of the proposed method for the robust determination of IVM in complex matrices.

Dutra et al.³⁰ demonstrated that direct dissolution of avermectins in methanol is robust and sufficient for the quality control of bulk samples. The specificity and selectivity of the method are ensured using a Phenomenex Gemini C18 chromatographic column 150 × 4.6 mm, 5 µm), which proved effective in the resolution of analytes and their separation from potential impurities or degradation products, thereby eliminating the need for solid-phase extraction steps or exhaustive interference studies.

In addition, it is important to highlight that an analysis of the data obtained from pharmaceutical samples was conducted using the t-student test to verify whether the values found significantly differ from the theoretical values for the drug samples. The proposed method demonstrated high precision in determining the mass of IVM (6 mg) in the medication, as the calculated t value (t_cal) of 1.38 and 1.19 for pharmaceutical samples A and B, respectively, lower than the tabulated t value (t_tab) equal to 4.30 exhibiting the reliable performance of the proposed method.

The performance of the proposed method was compared with those obtained in previous studies and the data are displayed in Table 2. The present study demonstrates that the SPCB/GCE exhibits good performance for the quantification of IVM. It is worth emphasizing that the SPCB/GCE demonstrates a low LOD. Although the LOD obtained in this study is higher when compared to some more complex modifications and costly materials reported in the literature, the developed methodology offers several key advantages. It stands out for its simplicity, costeffectiveness, and accessibility, making it an excellent choice for research environments with limited resources. Despite the modest increase in LOD, the sensor exhibits reliable efficiency and sensitivity in the detection of IVM, aligning perfectly with the need for practical yet high-performing analytical tools. This combination of affordability and reliable performance highlights the potential of this method for widespread adoption in various research and applied settings.

Table 2
Comparison of the analytical characteristics of the proposed method with other methods reported in the literature for IVM determination

Electrode	Technique	Linear range / (× 10-6 mol L-1)	LOD / (× 10-6 mol L-1)	Sample	Reference
BDD	FIA-AD	0.60-50	0.30	urine sample / pharmaceutical samples	12
GA2/GCE	DPV	0.999-110	2.66	urine sample / tap water	15
rGO/β-CD/GCE	DPV	0.5-40.0	0.25	tap water	14
AgNPs/B, S@rGO/GCE	DPV	0.0003-0.06	0.0001	injections / urine sample / tap water	1
LIGe	DPV	10-100	1.6	tap wate r/ urine sample / pharmaceutical sample	13
SPCB/GCE	DPV	10-100	1.3	tap water / urine sample / pharmaceutical sample	this work

Conclusions

The methodology developed in this study demonstrated promising results in the quantification of ivermectin, achieving a recovery rate close to 100% for water and urine samples. Additionally, the determination of ivermectin mass in tablets yielded values consistent with those stated on the packaging, confirming the precision of the method. The linear range of 10 to 100 μmol L^-1 showed the reliability and sensitivity of the sensor. Moreover, it is noteworthy that the preparation and modification of the electrode were executed in a simple and economical manner, utilizing accessible materials such as SPCB and DMF. This low-cost approach facilitates the implementation of the methodology in laboratories with limited infrastructure, making it a viable tool for environmental monitoring and quality control of pharmaceutical products. Thus, the results obtained not only validate the effectiveness of the proposed methodology but also emphasize its potential for practical applications, integrating simplicity, efficiency, and affordability into a single process.

Supplementary Information

Supplementary information is available free of charge at http://jbcs.sbq.org.br as file.

Acknowledgments

The authors are grateful to the Brazilian agencies: CAPES (Finance code 001, 88887.472618/2019-00-PROCAD-AM, 88887.658022/2021-00, 88887.704206/2022-00, 88887.691481/2022-00, and 88887.946541/2024-00), CNPq (315838/2021-3 and 408168/2025-0), FAPEMA (00901/22, 00930/22 and PQ-C-12477/25) and INCTBio-LK (CNPq grant 408338/2024-5) for the financial support.

Data Availability Statement

Data supporting the findings of this study are mostly presented in the article. Any further relevant data are available from the corresponding author upon reasonable request.

References

• ¹ Mahnashi, M. H.; Mahmoud, A. M.; Alkahtani, S. A.; El-Wekil, M. M.; J. Alloys Compd. 2021, 871, 159627. [Crossref]
  » Crossref
• ² Netto, M. S.; Pinto, D.; Franco, D. S. P.; Georgin, J.; Mallmann, E. S.; de Oliveira, A. H. P.; Silva, L. F. O.; Dotto, G. L.; Environ. Sci. Pollut. Res. 2023, 30, 95326. [Crossref]
  » Crossref
• ³ Sanderson, H.; Laird, B.; Pope, L.; Brain, R.; Wilson, C.; Johnson, D.; Bryning, G.; Peregrine, A. S.; Boxall, A.; Solomon, K.; Aquat. Toxicol. 2007, 85, 229. [Crossref]
  » Crossref
• ⁴ Garric, J.; Vollat, B.; Duis, K.; Péry, A.; Junker, T.; Ramil, M.; Fink, G.; Ternes, T. A.; Chemosphere 2007, 69, 903. [Crossref]
  » Crossref
• ⁵ Padivitage, N.; Adhikari, S.; Rustum, A. M.; Chromatographia 2021, 84, 989. [Crossref]
  » Crossref
• ⁶ Inoue, K.; Yoshimi, Y.; Hino, T.; Oka, H.; J. Sep. Sci. 2009, 32, 3596. [Crossref]
  » Crossref
• ⁷ Mullapudi, T. V. R.; Ravi, P. R.; Thipparapu, G.; J. Anal. Sci. Technol. 2023, 14, 44. [Crossref]
  » Crossref
• ⁸ Suvarna, V.; J. AOAC Int. 2023, 106, 534. [Crossref]
  » Crossref
• ⁹ Kowalski, P.; Bieniecki, M.; Olȩdzka, I.; Lamparczyk, H.; Biomed. Chromatogr. 2004, 18, 302. [Crossref]
  » Crossref
• ¹⁰ Samsonova, J. V.; Baxter, G. A.; Crooks, S. R.; Small, A. E.; Elliott, C. T.; Biosens. Bioelectron. 2002, 17, 523. [Crossref]
  » Crossref
• ¹¹ Galli, A.; De Souza, D.; Garbellini, G. S.; Coutinho, C. F. B.; Mazo, L. H.; Avaca, L. A.; Machado, S. A. S.; Quim. Nova 2006, 29, 105. [Crossref]
  » Crossref
• ¹² Lourencao, B. C.; Medeiros, R. A.; Thomasi, S. S.; Ferreira, A. G.; Rocha-Filho, R. C.; Fatibello-Filho, O.; Sens. Actuators, B 2016, 222, 181. [Crossref]
  » Crossref
• ¹³ Ferreira, D. C. M.; Inoque, N. I. G.; Tanaka, A. A.; Dantas, L. M. F.; Muñoz, R. A. A.; da Silva, I. S.; Anal. Methods 2024, 16, 4136. [Crossref]
  » Crossref
• ¹⁴ Silva, M. K. L.; Simões, R. P.; Leão, A. L.; Lapa, R. M. L.; Rascón, J.; Cesarino, I.; Electroanalysis 2023, 35, e202100649. [Crossref]
  » Crossref
• ¹⁵ Koçak, B.; İpek, Y.; Electrocatalysis 2022, 13, 108. [Crossref]
  » Crossref
• ¹⁶ Youssry, M.; Madec, L.; Soudan, P.; Cerbelaud, M.; Guyomard, D.; Lestriez, B.; Phys. Chem. Chem. Phys. 2013, 15, 14476. [Crossref]
  » Crossref
• ¹⁷ Silva, T. A.; Moraes, F. C.; Janegitz, B. C.; Fatibello-Filho, O.; J. Nanomater. 2017, 2017, ID 4571614. [Crossref]
  » Crossref
• ¹⁸ Fort, C. I.; Ortiz, R.; Cotet, L. C.; Danciu, V.; Popescu, I. C.; Gorton, L.; Electroanalysis 2016, 28, 2311. [Crossref]
  » Crossref
• ¹⁹ Fort, C. I.; Cotet, L. C.; Vasiliu, F.; Marginean, P.; Danciu, V.; Popescu, I. C.; Mater. Chem. Phys. 2016, 172, 179. [Crossref]
  » Crossref
• ²⁰ Fort, C. I.; Rusu, M. M.; Cotet, L. C.; Vulpoi, A.; Florea, I.; Tuseau-Nenez, S.; Baia, M.; Baibarac, M.; Baia, L.; Molecules 2020, 26, 117. [Crossref]
  » Crossref
• ²¹ Long, C. M.; Nascarella, M. A.; Valberg, P. A.; Environ. Pollut. 2013, 181, 271. [Crossref]
  » Crossref
• ²² Rusu, M. M.; Fort, C. I.; Cotet, L. C.; Vulpoi, A.; Todea, M.; Turdean, G. L.; Danciu, V.; Popescu, I. C.; Baia, L.; Sens. Actuators, B 2018, 268, 398. [Crossref]
  » Crossref
• ²³ Castro, L. N.; Lopes, C. E. C.; Santos-Neto, D. R.; Silva, L. R. G.; Tanaka, A. A.; Dantas, L. M. F.; da Silva, I. S.; Ionics 2024, 30, 7575. [Crossref]
  » Crossref
• ²⁴ Santos-Neto, D. R.; Lopes, C. E. C.; Silva, G. P.; Castro, L. N.; Silva, J. P. C.; Ferreira, D. C. M.; Silva, L. R. G.; Dantas, L. M. F.; da Silva, I. S.; Anal. Methods 2024, 16, 6271. [Crossref]
  » Crossref
• ²⁵ Łysoń, M.; Górska, A.; Paczosa-Bator, B.; Piech, R.; Electrocatalysis 2021, 12, 641. [Crossref]
  » Crossref
• ²⁶ Laube, N.; Mohr, B.; Hesse, A.; J. Cryst. Growth 2001, 233, 367. [Crossref]
  » Crossref
• ²⁷ Silva, J. P. C.; Santos-Neto, D. R.; Lopes, C. E. C.; Silva, L. R. G.; Dantas, L. M. F.; da Silva, I. S.; J. Solid State Electrochem. 2025, 29, 1013. [Crossref]
  » Crossref
• ²⁸ Wang, J.; Study of Electrode Reactions and Interfacial Properties, 3^rd ed.; John Wiley & Sons, Inc.: New Jersey, USA, 2006.
• ²⁹ Mocak, J.; Bond, A. M.; Mitchell, S.; Scollary, G.; Pure Appl. Chem. 1997, 69, 297. [Crossref]
  » Crossref
• ³⁰ Dutra, F. V. A.; Teixeira, L. S.; Pires, B. C.; Florez, D. H. Â.; Teixeira, R. A.; Borges, K. B.; Braz. J. Pharm. Sci. 2022, 58, e19587. [Crossref]
  » Crossref

Edited by

• Editor handled this article:
  Andrea R. Chaves (Executive)

Publication Dates

• Publication in this collection
  09 Mar 2026
• Date of issue
  2026

History

• Received
  07 Nov 2025
• Accepted
  26 Jan 2026