Electrochemical techniques as valuable analytical tools for improved drug monitoring


Paracetamol (PCT) is a non-steroidal anti-inflammatory drug used to treat fever, pain, and inflammation. However, PCT overdose is dangerous and often leads to severe liver damage and, in extreme cases, liver failure. Additionally, environmental traces of PCT from medical waste highlight the need for precise analytical methods for its detection and quantification. Traditional analytical techniques such as liquid chromatography and mass spectrometry, although accurate, are often limited by high operational costs and complex sample preparation. On the other hand, electrochemical techniques using chemically modified electrodes offer a cost-effective analytical alternative with benefits in simplicity, speed, and sensitivity. Among these, carbon paste electrodes (CPE), modified with various materials have been studied for their efficient electrochemical properties. To this end, a new study was published in the International Journal of Molecular Sciences, conducted by Dr. Moaad Gharous, Dr. Loubna Bounab, Dr. Mohamed Choukairi from the Abdelmalek Essaadi University alongside Dr. Fernando J. Pereira, Dr. Roberto López and Dr. A. Javier Aller from the University of León in Spain, where the researchers developed a new electrochemical method for detecting PCT using a modified CPE incorporated with stevensite clay (Stv-CPE).

The team prepared the new Stv-CPE electrode by mixing graphite powder with stevensite clay and a binding agent (mineral oil) to form a homogeneous paste. This mixture was then packed into a plastic electrode casing with a copper wire to establish an electrical connection. The authors used Fourier-Transform infrared spectroscopy (FT-IR) to identify the functional groups present in the stevensite clay and confirmed that it is predominantly composed of silica with traces of magnesium, aluminum, iron, and calcium oxides. They also used scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDS) to provide detailed structural images of the clay’s morphology and elemental composition, demonstrating their small particle size and confirming the elemental makeup of the clay. Indeed, the FT-IR spectroscopy and SEM/EDS analyses confirmed the clay’s composition and morphology, which are critical parameters for electrochemical application. The small particle size (~50 nm) and high porosity enhance its suitability as a modifier due to improved surface area and electron transfer capabilities.

Moreover, the authors used cyclic voltammetry to assess the electrochemical behavior of the electrode in different buffer solutions and under varying conditions to optimize the electrode’s response to PCT. Furthermore, advanced techniques such as differential pulse voltammetry and electrochemical impedance spectroscopy were employed to refine further the understanding of the electrochemical properties of the modified electrode, including its sensitivity and stability.

The researchers systematically tested different compositions of the carbon paste to determine the optimal amount of stevensite clay that would provide the best electrochemical response. They evaluated the performance of the electrode under different experimental conditions, such as pH levels and buffer compositions, to establish the most favorable conditions for detecting PCT. They validated the electrode’s efficiency by testing it against standard solutions of PCT and spiked serum samples, ensuring the method’s reliability and accuracy. Tests were conducted in the presence of common interfering substances such as dopamine and tyrosine to assess further the selectivity of the electrode. In these studies, the authors found that the optimal clay content in the electrode was determined to be 15%, which provided the best balance between sensitivity and stability of the electrochemical response. They also demonstrated that the modified electrode has a low detection limit of 0.2 µM and a quantitation limit of 0.5 µM for PCT, making it highly suitable for detecting low concentrations of PCT in complex biological and pharmaceutical samples. Moreover, the electrode showed a robust linear response for PCT concentrations ranging from 0.5 µM to 100 µM, suitable for various analytical needs. This high degree of sensitivity and specificity is crucial for accurate diagnostics and environmental monitoring, ensuring that even minute quantities of contaminants can be detected and quantified effectively.

From a theoretical electrochemical point of view, even though the electrode processes show a complex kinetic behaviour, a thorough evaluation of the developed electrode kinetics was possible by the study of the CV waves, which allowed us to derive valuable information, very helpful for a better understanding of the redox cathodic and anodic processes. Thus, according to the kinetic calculations, this electrochemical system shows a predominant diffusion process as the most predominant mass transfer mechanism with good electronic transport properties and some degree of irreversibility in the electrode processes. The good electrochemical activity concerning the PCT redox reaction relates to the favourable π–π and π-n interactions between the PCT molecules and the π system of the Stv material. Thus, the planar PCT molecule has a structurally extensive conjugated system with improved reactivity compared to usual. Further, the conjugation process in the PCT molecule significantly reduces the basicity of the hydroxyl oxygen and amide nitrogen. Consequently, the amide group acts more as a hydrogen bond donor, whereas the carbonyl group acts as a hydrogen bond acceptor. However, the hydroxyl group can act as a donor and acceptor, which facilitates the formation of intra- and inter-molecular hydrogen bridges, particularly with the OH groups in Stv.

Furthermore, given the widespread use of PCT and its subsequent presence in environmental waters, there is a growing need to monitor pharmaceutical pollutants effectively. The study provides a tool for environmental scientists to detect and quantify pharmaceutical residues in water bodies, aiding in the assessment of pollution levels and the effectiveness of water treatment processes. This methodology is essential for maintaining ecological balance and ensuring the health of aquatic life. It is worth mentioning that the new method was successfully applied to quantify PCT in human serum samples and commercial tablet formulations, demonstrating its efficacy in complex matrices without significant interference from other components. Clinically, the ability to rapidly measure PCT levels in human serum can be vital in cases of suspected overdose or in managing therapeutic dosing. This developed method can potentially be integrated into clinical settings to provide quick feedback on drug levels, enhancing patient safety and treatment efficacy. In pharmaceutical manufacturing, this technique can be employed for quality control, ensuring that products meet specified standards without the need for more elaborate testing procedures. Additionally, the electrochemical approach developed in this study could be adapted to detect other drugs and biochemical agents, broadening its utility beyond just PCT. This adaptability makes it a versatile tool in the development of detection technologies for a wide range of substances, potentially leading to innovations in both environmental science and medical diagnostics.

Overall, the developed Stv-CPE-based electrode exhibited excellent selectivity when tested against potential interfering substances. Furthermore, the electrode showed good reproducibility and stability, indicating its potential for repeated use in routine analytical applications. These findings suggest that the developed voltammetric method by Abdelmalek Essaadi University and University of León researchers using a stevensite clay-modified carbon paste electrode is a practical, reliable, and economical option for the quantification of PCT in various environmental and clinical settings. Future studies could explore the method’s application to other pharmaceutical compounds and potential improvements in electrode design for enhanced sensitivity and selectivity.

About the author

Professor Dr. A.J. Aller studied Chemical Sciences at the University of Valladolid (UVA), obtaining his Bachelor’s Degree in 1976. In 1981, he presented his PhD thesis at the UVA under the supervision of Professor Dr. José Luis Bernal Yagüe of the Department of Analytical Chemistry. After four and a half years working in the powder metallurgical industry (Polmetasa, S.A., Mondragón, Guipúzcoa, Spain), in 1984, I became part of the Department of Biochemistry and Molecular Biology (Analytical Chemistry Area) of the University of León (ULE) as an associate professor. In 1987, he obtained the position of University Professor in Analytical Chemistry in the same department, while in 2003, he became Full Professor at the ULE. In 1985, he was a visiting professor at the University of Aberdeen (Scotland) with Professor Malcolm S. Cresser. Currently, he is linked as Professor Emeritus to the ULE and as Associate Editor of the journal Environmental Monitoring and Assessment. Professor Aller has received funding through 16 research projects and has published more than 130 articles in scientific journals, 5 books and 8 book chapters. Most of his research interest has focused on the development and applications of analytical spectroscopy. One of the main points discussed relates to the mechanisms of interference and its consequences in the analytical applications of electrothermal atomization atomic absorption spectrometry. Another scientific aspect of interest includes the use of bacteria as analytical tools, combining them with the use of atomic and molecular spectrometry techniques. More recently, Prof. Aller’s research has focused on the characterization of natural and synthetic nanoparticles using diverse surface analysis techniques. Prof Aller was awarded a Special Mention in the V Professor Antonio Hidalgo Award (Perkin Elmer, 1995) for the best contribution in Instrumental Analysis for their work on Bacteria immobilized in the separation of toxic elements.

About the author

F.J. Pereira concluded the Environmental Sciences degree at University of León with good marks. In 2009, he was granted with an autonomic competitive contract to start his doctoral studies, which finished in 2015, obtaining a PhD in Analytical Chemistry. Synthesis and characterization of different ceramic nanomaterials were studied, and, as a result, some applications of theses nanomaterials were evaluated. Among them, analytical improvements, luminescence and adsorptive properties were considered remarkable. In order to carry out these investigations, F.J. Pereira learned and applied different analytical techniques, among which are Electronic Microscopies, both Scanning (SEM) and Transmission (TEM), X-ray Dispersive Energy Spectroscopy (EDS), Raman, Fourier Transform Infrared (FT-IR) and Fluorescence spectroscopies, Induction Coupled Plasma Mass Spectrometry (ICP-MS), and Voltammetric techniques.

In 2016, F.J. Pereira started working as an associate professor in Analytical Chemistry area in Universidad de León, developed the assigned teaching, and continued with his predoctoral research line. In 2017 he obtained a position as assistant professor in the area mentioned above and his research broadened: atomic and molecular spectroscopic characterization of antique inks, Raman spectroscopy and computational studies of inorganic and organometallic arsenic compounds, and drug chromatographic separations were studied. As the result of his previous and actual positions, 23 JCR manuscripts are been published, all located in the first tercile (T1) of their respective areas.

About the author

R. López

In 2007, I finished Chemical Engineering at Universidad Complutense de Madrid with distinction. From 2010 to 2018, I worked as chemical engineering and materials science adjunct professor at Universidad de León. In 2015, I obtained a PhD in Chemical Engineering on the oxy-combustion of agroenergetic materials. Transport phenomena of oxidation of biomass were studied in detailed. As a result, some mathematical models and industrial simulations were performed to discuss and optimize the oxidation process.

Since 2008, I have been in touch with some colleagues involved in biomedicine research fields. In this frame, my contributions lie in the analysis of the physicochemical interactions between several compounds used in chemotherapy and radiotherapy and the human cells. From 2018, my position as assistant professor, and from 2022 as associate professor, in Physical Chemistry area in Universidad de León has allowed me to improve my knowledge on Quantum Chemical Topology and the use of the Interaction Quantum Atoms to a better inspection of the reactivity of biomolecules.

As the result of my previous positions, I have published 32 JCR manuscripts and I have supervised 30 master thesis and 2 doctoral theses.

About the author

Mr. Choukairi, holder of a doctorate in electro-analytical chemistry obtained in 2018 at the Faculty of Sciences of the Abdelmalek Essaadi University of Tetouan, with honors, under the title: design and application of electrochemical sensors for teaching oxidative stress in environmental and biological environments. In 2019, Mr. Choukairi joined Abdelmalek Essaadi University as a associate professor in the chemistry department of the Faculty of Sciences of Tetouan. During this period, he taught the courses of the major modules as well as the practical and supervised work of these modules, while continuing the enhanced research during his doctorate. In 2023, he obtained his university accreditation and was appointed accredited lecturer in the same year. As a researcher, Professor Choukairi continued to deepen his research work within the Laboratory of Materials and Sustainable Energy Engineering (LMESE), which resulted in the publication of several articles in reputable international journals . In 2024, Professor Choukairi is appointed head of the chemistry department at the Faculty of Sciences of Tetouan. His work has focused on various aspects of modified electrodes, electrochemical analysis, chemical synthesis and theoretical studies. In particular, he developed methods for preparing and modifying chemically modified electrodes using different materials and components. The application of these modified electrodes as electrochemical sensors for the detection and quantification of medical, pharmaceutical and environmental molecules has been at the heart of his work. Additionally, he conducted extensive kinetic and theoretical studies on electrochemical processes.

About the author

Loubna Bounab is a Doctor in Materials and environment engineering. Actually, she is:

  • Researcher and professor at National School of Applied Sciences (ENSAT), Abdelmalek Essaadi University, Morocco.
  • Head of the Department of Industrial and Civil Sciences and Technologies (STIC)
  • Head of research group Advanced Materials and Civil engineering (MASGC).
  • Author or co-author of numerous articles on Materials, electrochemistry and civil engineering
  • Team member of many research (Horizon 2020) and capacity building (Erasmus+) projects.
  • Member of expert committees on career pathways evaluations.
  • Supervisor and member of the jury for several thesis.
  • Author and co-author of several scientific publications in the field of electrochemistry and materials.
  • Member of scientific and organizing committees of several national and international scientific events.

About the author

Moaad Gharous

After completing a two-year master’s degree in materials physics at the Faculty of Science at Abdelmalek Essaadi University, M. Gharous joined the doctoral programme at the National School of Applied Sciences at the same university. During his doctorate, M. Gharous carried out two research placements in Spain, a 5-month placement at the University of Leon and a 3-month placement at the University of Seville. Under an agreement with the Abdelmalek Essaadi University and the Autonomous University of Madrid, M. Gharous is preparing his doctoral thesis entitled: Elaboration of new carbon-based materials for the degradation and electrochemical detection of antibiotics. The PhD student has participated in several international conferences with work under the titles: Design and preparation of electrochemical sensors based on clay nanoparticles for various applications, Electrodes modified by nanomaterials: Elaboration and application in electroanalysis, Electrochemical sensor for the detection of analgesic molecules in biological fluids and pharmaceutical formulations. M. Gharous has works published in indexed journals, A Carbon Paste Electrode Modified by Bentonite and l-Cysteine for Simultaneous Determination of Ascorbic and Uric Acids: Application in Biological Fluids, Electrochemical Kinetics and Detection of Paracetamol by Stevensite-Modified Carbon Paste Electrode in Biological Fluids and Pharmaceutical Formulations, and Methionine-stevensite derived bionanocomposite: A green and efficient adsorbent for the elimination of antibiotics.


Gharous M, Bounab L, Pereira FJ, Choukairi M, López R, Aller AJ. Electrochemical Kinetics and Detection of Paracetamol by Stevensite-Modified Carbon Paste Electrode in Biological Fluids and Pharmaceutical Formulations. Int J Mol Sci. 2023 ;24(14):11269. doi: 10.3390/ijms241411269.

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