Nanomaterial-Based Electrochemical Sensors for the Detection of Pharmaceutical Drugs

Abstract

The rapidly increasing human population has led to new biological and environmental challenges. These challenges, in turn, have contributed to the rapid growth of the pharmaceutical sector. Quality control in pharmaceutical manufacturing and drug delivery necessitates portable, sensitive, precise, and cost-effective devices to monitor patient dosing and assess pharmaceutical hazards. This study highlights the attributes and applications of the current nanomaterial-based sensors for drug detection, emphasizing the potential of these devices to advance the detection of bioactive molecules, thereby promoting human health and environmental protection on a large scale. Electrochemical sensors, in particular, have become invaluable in bioimaging, electrochemical analysis, and drug delivery due to their high specificity, selectivity, and stability across cycles. This review focuses on recent advancements in electrochemical devices for healthcare applications, detailing their production, analytical performance, and clinical uses.

1. Introduction

There is increasing interest in the utilization of electrochemical sensors and drug delivery platforms in personalized healthcare and point-of-care (POC) diagnostics [1,2]. These devices demonstrate versatility, non-invasive application, safety, implantability/wearability, a lightweight structure, and cost-effectiveness. The development of integrated platforms capable of operating in direct conjunction with biological systems—whether remotely, on epithelial surfaces, or within soft tissue—is paramount in achieving precise and reliable real-time assessments of physiological parameters or biomarker concentrations [3]. Such parameters encompass the pH, temperature, heart rate, neurophysiological signals, and blood pressure. These electrochemical sensors are characterized by their non-toxic nature and exhibit a minimal immunogenic response upon integration into biological matrices, thereby ensuring biocompatibility [4] and ease of fabrication [5,6,7].

The development of flexible (bio)sensors often eschews the incorporation of complex substrates, in contrast to conventionally fabricated rigid sensing devices, in response to end-user demands for portable or self-screening solutions [8,9]. The analytical efficacy of these proposed sensors is markedly enhanced through the utilization of advanced transducer materials in the primary sensing element [10,11]. Due to their mechanical properties and material characteristics, paper-based and fabric-integrated detection devices are particularly attractive, as they can be readily modified with nanomaterials and biomolecules [12,13]. Autonomous micro- and nanoscale machines are increasingly integrated into biomedical instrumentation for targeted drug delivery and diagnostics [14]. Biorecognition components are pivotal in ensuring the analytical performance of biosensors, supplemented by novel interface materials such as engineered nanoobjects—especially nanoparticles—employed as immobilization and detection platforms, alongside contemporary carbon-based nanomaterials like graphene and its analogs. Newly synthesized polymers and copolymers are proposed as effective matrices for the immobilization of active components and the enhancement of sensor signal transduction [15,16].

The comprehensive market for pharmacological enterprises was appraised at approximately USD 1.25 trillion in 2019, with projections indicating a surge to USD 1.64 trillion by 2025, driven by the escalating human population. A contextual analysis reveals that pharmaceutical transactions increased by 358.5% from 2005 to 2024 [16]. The pervasive misapplication and abuse of pharmaceuticals have culminated in two critical dilemmas: (i) the imperative need for cost-effective, portable, and precise sensors applicable to diverse practical contexts and (ii) the necessity to monitor and mitigate pharmaceutical contamination in aquatic environments to safeguard both human and ecological health. The demand for affordable, portable, and accurate sensors in clinical contexts is underscored by the rapid advancement of precise diagnostic modalities for infectious diseases, which have markedly influenced global health paradigms. Recent innovations in miniaturized biosensor technologies tailored to point-of-care (POC) testing have yielded significantly enhanced sensitivity, reliability, rapidity, and cost-effectiveness in detection methodologies, obviating the requirement for elaborate instrumentation. These advancements have facilitated the development of user-ready devices that are now available on the market. Moreover, wearable sensors for kinematic tracking have emerged as promising instruments in rehabilitative medicine, enabling the systematic quantification of motor behavior across diverse patient demographics. These devices enhance remote monitoring and telerehabilitation, augmenting care for individuals with neurological or musculoskeletal disorders. The confluence of big data sourced from these applications propels the transition towards personalized and precision medicine. In sweat analysis, flexible, wearable sweat sensors facilitate the continuous, real-time, non-invasive monitoring of sweat analytes, yielding insights into human physiological states. Electrochemical sensors are particularly suitable for these applications due to their superior performance, cost-effectiveness, and extensive applicability. Collectively, advancements in biosensor technology enhance the diagnostic capabilities and optimize the efficiency and efficacy of clinical practices, establishing them as indispensable instruments in contemporary healthcare [11].

The laxity in the regulatory frameworks governing prescription pharmaceuticals and the enforcement of corresponding laws has precipitated a critical epidemic of drug overdoses across numerous nations. For instance, data from the National Center for Health Statistics indicated that, from February 2018 to February 2019, there were 69,029 reported fatalities attributable to overdoses of non-steroidal anti-inflammatory drugs (NSAIDs), representing a 5.5% increase from the previous year [17]. Furthermore, in 2017, over 5000 deaths were documented due to antidepressant overdoses, in contrast to 3889 in 2010, with the US National Center for Health Statistics reporting a consistent annual increment of approximately 6% in mortality associated with antidepressant overdoses from 2005 to 2018. A report from the German Service for the Climate revealed the presence of 203 pharmaceuticals, encompassing significant concentrations, within the aquatic ecosystems of 71 distinct nations. The majority consisted of analgesics, antibiotics, and anti-inflammatory and antifungal agents. Notably, the concentrations of antibiotics in 37 rivers subjected to analysis by Japanese health authorities reached levels as high as 626 ng/L [18]. However, traditional detection methodologies remain constrained due to their high costs and limited mobility. Consequently, electrochemical detection techniques have emerged as promising alternatives to conventional methods [3]. The integration of nanomaterials has significantly enhanced the development of electrochemical sensors; these nanomaterials can be engineered with tunable morphologies, dimensions, surface charges, and physical and chemical properties. This versatility allows for the tailored adjustment of specific nanomaterials to optimize their efficacy in detecting diverse analytes. To fully exploit the capabilities of contemporary electrochemical sensors, a comprehensive understanding of the physicochemical and electrostatic interactions at the interfaces between nanomaterial-based electrodes and target analytes is essential. This knowledge is crucial in detecting vital pharmaceutical compounds, including analgesics, stimulants, antibacterials, antivirals, antifungals, and anticancer agents.

Biosensing technology has undergone significant advancement since the inception of the first biosensor utilizing glucose oxidase in the 20th century [19,20]. It has evolved into a multidisciplinary field that integrates aspects of human physiology with environmental science [21,22,23,24]. Biosensors find utility across various interdisciplinary domains, including medicine, materials science, and biological research [25,26]. Despite notable progress aimed at enhancing biosensors’ efficacy, these devices remain susceptible to background interference within reaction samples, which can introduce measurement bias and uncertainty. Consequently, it is imperative to develop alternative analytical methodologies to overcome the limitations inherent in conventional biosensors [27]. Electrochemical sensing has emerged as a promising analytical technique, extensively employed in clinical, biological, and pharmacological investigations. Electrochemical sensors offer several advantages over alternative methods, notably their ease of miniaturization, operational simplicity, and cost-effectiveness in detection [28,29,30].

Furthermore, designs incorporating integrated electrochemical transducers are often characterized by portability, disposability, and user accessibility [31,32,33]. The advent of simultaneous physiological monitoring through electrochemical biosensors has facilitated the detection of specific biomarkers within human biological fluids [34,35], enabling their identification via wireless data acquisition systems [36,37,38]. High-performance electrochemical biosensors enhance the electronic conductivity, accelerating advancements in diagnostic assays, environmental surveillance, and pharmaceutical applications [39,40]. An extensive body of literature has emerged that evaluates electrochemical sensors from diverse perspectives, particularly with novel materials and specialized fabrication methodologies [41]. We have synthesized a comprehensive overview of the analytical performance metrics and electrochemical device fabrication techniques employed to achieve targeted enhancements in sensitivity and selectivity [42]. The applications of these electrochemical sensors were then systematically analyzed, emphasizing their innovative roles in human healthcare, including wearable sensor technology, disease diagnostics, and pharmacological screening. Lastly, a concise discourse is presented regarding the prospective developments and challenges associated with electrochemical technologies (Figure 1).

1.1. Electrochemical Methods

Various electroanalytical techniques can be used for the electrochemical detection of drugs. Specific methods might be more appropriate for distinguishing drug accumulation in light of explicit electrochemical connection points between the nanomaterials utilized, the analytes of interest, and the typical application. Examples of popular electrochemical systems include voltammetry, electrochemical impedance spectroscopy (EIS), potentiometry, and amperometry. The cyclic voltammetry (CV) technique measures the current by varying the applied potential of the working electrode during forward and reverse scans. CV can be used to calculate the response current, considering the stoichiometry, number of electrons transferred, and reversibility [43]. The dissemination coefficient, charge move coefficient, and initiation boundary may also be determined using this approach, which helps to clarify the framework’s response energy. For electrochemical research, beat methods, including square wave voltammetry (SWV), differential pulse voltammetry (DPV), and normal pulse voltammetry (NPV), are more frequently utilized because of their rapid response compared to CV. The Faradaic reply under mobility and linear distribution circumstances is displayed just after the root of the capacitance current by the Cottrell condition, intending for the Faradaic current to be substituted proportionally to the time [44]. DPV is typically suitable to obtain location cutoff points of 10⁻⁸ M or lower. NPV and DPV both utilize a series of potential pulses; however, DPV differs in that it applies a fixed pulse amplitude superimposed onto a gradually increasing potential range, instead of progressively increasing the pulse amplitude, as in NPV. The current is estimated not long before the utilization of each pulse and towards the end of each pulse. The boundaries, especially the beat width and number, are essential for these pulse methods to enhance the sign reaction [45]. The material used significantly impacts how the beat width and number are enhanced. The number may need to be lowered to remove a sizeable capacitive current from a detecting substrate with high capacitance. Conversely, the beat width may need to be increased for more delicate detection. Even if there are more oxidation/decrease actions occurring at the surface, for sensing phases with large surfaces in particular, the capacitive current may overcome any Faradaic current as it slowly decomposes. This issue could be resolved by using a lower pulse amplitude; however, this may decrease the Faradaic response. One more dominant electrochemical method for detection applications is SWV. This method, as its name implies, utilizes a square wave superimposed on a staircase-like potential, similar to differential pulse voltammetry (DPV). The square wave features both forward and reverse pulses. The difference between the resulting forward and reverse currents is then plotted against the staircase potential to generate the final measurement [46]. The benefit of SWV, as opposed to DPV, is the elimination of capacitive limitations while removing the forward beat from the opposite beat, bringing about more refined identification limits. SWV is likewise helpful in clarifying the terminal energy for some responses by utilizing a fast output rate (~1 V/s) and a quick information assortment speed combined with PC handling. This strategy has a few limits because of its swift sweep rate; SWV is more suitable for examining reversible and fast terminal cycles and those combined with quick substance responses, rather than for semi-reversible responses with low cathode energy. A higher capacitive current in a material can cause more significant peaks in the Faradaic reaction. Amperometric sensors depend on ongoing estimation at an applied cathode potential; they display a few main benefits—for example, a low location breaking point and high selectivity, contrasting with voltammetry-based electrochemical sensors [47]. Due to their excellent responsiveness and selectivity, protein-based amperometric sensors have received much attention [48]. Safety is a major concern in enzymatic electrochemical monitoring, as factors such as protein denaturation, sample array clogging, and interference from microorganisms can impact the reliability.

CV and DPV are widely used in drug detection due to their ability to identify and quantify drugs at low concentrations, particularly when integrated with nanomaterial-based sensors. One study focused on the electrochemical determination of novel psychoactive substances, specifically examining the electroanalytical behavior of compounds such as 25B-NBOMe, benzylpiperazine, 1-(3-chlorophenyl)piperazine, and N,N-dimethyltryptamine. Utilizing DPV on boron-doped diamond electrodes, the researchers achieved high sensitivity in their measurements. The detection limits for these compounds ranged from 0.15 μg/mL to 1.8 μg/mL, indicating the method’s effectiveness. Additionally, the technique was used to successfully analyze spiked oral fluid samples, with impressive recovery rates ranging between 98% and 103% [32].

A recent study explored the simultaneous electrochemical determination of non-steroidal anti-inflammatory drugs using innovative electrode materials. Specifically, the researchers employed a combination of fullerene–carbon nanofiber and graphene–carbon nanotube paste electrodes to detect three common medications: diclofenac, naproxen, and ibuprofen. Utilizing the DPV technique, they achieved impressive detection limits—0.230 nM for diclofenac, 0.310 nM for naproxen, and 0.180 nM for ibuprofen. The results indicated robust reproducibility and stability when tested with real surface water samples, showcasing the efficacy of these electrodes in environmental monitoring [34]. A square wave cathodic adsorptive stripping voltammetric method was developed to detect nitrofurantoin. This method demonstrated a well-defined reduction peak, attributed to the reduction of the -NO₂ group present in the compound. Notably, it showcased a linear concentration range of 2 × 10⁻⁵ to 1 × 10⁻⁷ mol L⁻¹, highlighting its sensitivity. With a limit of detection of just 0.06 ng/mL, the method proved to be highly effective in identifying this toxic drug [36].

A novel biosensor was developed to detect acetaminophen in human blood, utilizing a combination of ruthenium-doped vanadium carbide and a polymeric nanohybrid. Through the application of CV and DPV, this biosensor demonstrated impressive performance, achieving a detection limit of 0.024 μM. Furthermore, it operated effectively within a linear range of 0.1 to 382.72 μM. Notably, the biosensor showed reasonable recovery rates in human blood samples, underscoring its potential for practical application in clinical settings [38]. A dual-functional sensor was developed to detect and degrade tetracycline, which utilized silver-doped zinc ferrite embedded in chitosan-functionalized carbon nanofibers. Electrochemical tests demonstrated the sensor’s impressive capabilities, showing a low detection limit of 1 nM and a wide linear range of 0.2 to 53.2 μM. Furthermore, it exhibited high recovery values in real environmental and food samples, underscoring its effectiveness in monitoring this antibiotic [39].

Atenolol was determined in pharmaceutical formulations using a gold nanoparticle-modified indium tin oxide electrode. This innovative method utilized DPV, which had been shown to produce a linear calibration curve within the range of 0.5 μM to 1.0 mM. Notably, the detection limit was established at an impressive 0.13 μM. Additionally, the recovery rates for this technique fell between 95.7% and 105.2%, indicating its reliability for quantitative analysis in both drug formulations and urine samples [41]. The voltammetric methods, combined with nanomaterial-modified electrodes, provide the specificity, sensitivity, and low detection limits needed for practical drug detection across pharmaceuticals, environmental safety, and clinical diagnostics.

1.2. Electrochemical Sensors

A major subgroup of substance sensors is represented by electrochemical sensors. A substance sensor is a tool that uses systems-based data on the chemical qualities of the area. A compound delivers specific reactivity that is directly relevant to the concentration of a particular chemical in various species. The sensor element is the central point of a sensor. In an unusual scenario, the sensor identifies and links to the species as it interfaces with an identifier. A quantifiable result signal is constituted by the identifiers using a substance signal transmitted by the sensor component for the targeted species [49]. The cathode serves as the critical indicator component in electrochemical sensors. An electro-coagulation sensor consists of a counter electrode and receiving cathode isolated by a thin electrolyte layer [50]. Electrochemical sensors usually operate by using the cathode surface species’ redox reaction to generate an electrical signal, analogous to gathering the analyte species. The reference electrode is placed inside the electrolyte setup, in close proximity to the working electrode, in a sensor that needs an additional voltage to function and maintain the working electrode’s performance. In an ideal situation, no specific current flows between the reference terminal and the functional cathode. Generally speaking, a suitable sensor should have the following characteristics [51]: (1) the signal result must be adequate for the species and size of the target group; (2) it must identify the species; (3) it must set high standards and be extremely selective; (4) it must be highly precise and repeatable; (5) it must have a quick response time for a brief period; (6) it must exhibit a lack of response to ecological factors such as the temperature and ionic strength. Such sensors have reached the commercial stage. Currently, they stand out among the sensors that are in use. For instance, glucose meters with electrochemical sensors can measure the blood glucose levels in diabetics. The idea behind these devices is an enzymatic reaction that is used to calculate blood glucose. According to [52,53], electrochemical sensors may be divided into the following five classes: conductometric sensors, amperometric sensors, impedimetric sensors, voltammetric sensors, and potentiometric sensors. Electrochemical sensors are classified as coulometric and electrochemiluminescence sensors in some cases.

2. Novel Materials for Sensors

2.1. Significance of Nanomaterials in Electrochemical Sensing

The product that completes the identification step requires an excellent and reliable electrochemical sensor. As a result, nanomaterials have several advantages in sensor development that support the electrochemical stage. Given the characteristics of the nanoscale, sensors have several advantages over other types of devices, including their tiny size, high awareness, and selectivity. Different nanomaterials have unique features, such as a large surface area, conductivity, and strong chemical properties, enabling them to interact synergistically with analytes, playing a critical role in enhancing drug detection.

i. Large Surface Area: Nanomaterials have an exceptionally large surface-to-volume ratio, providing more active sites for the adsorption of analyte molecules. This increased interaction area maximizes the binding of drug molecules, improving the sensor’s sensitivity. An enhanced surface area also means that more analyte molecules can be captured simultaneously, enabling detection even at low concentrations. This is crucial for the monitoring of trace levels of pharmaceutical compounds.

ii. Enhanced Conductivity: Many nanomaterials, such as carbon nanotubes, graphene, and metal nanoparticles, exhibit excellent electrical conductivity, essential for electrochemical sensors. High conductivity facilitates the rapid transfer of electrons between the nanomaterial and the analyte, which can lead to quick and precise current responses in electrochemical sensors. This rapid electron transfer enhances the detection limit, enabling fast response times and high sensitivity to the presence of drugs in a sample.

iii. Chemical Functionalization and Selectivity: Nanomaterials can be chemically modified to have specific functional groups that selectively interact with particular drug molecules on their surfaces. For instance, surface modifications with functional groups like carboxyl, amino, or thiol can create more robust, selective bonds with target drugs. This selective affinity improves the detection specificity, allowing sensors to distinguish between similar molecules, reducing false positives, and improving the accuracy.

These properties, in combination, make nanomaterial-based sensors highly effective in drug detection by maximizing the sensitivity, selectivity, and response speed, which is crucial for healthcare and environmental monitoring applications. The following can be used as examples of noteworthy nanosensor qualities: • More modest and less expensive; • Increased surface region of the terminal; • Increased pace of mass exchange; • Quick electron movement, in contrast with cathodes, in light of mass materials; • Further developed selectivity; • Greater awareness; • Increased reaction to excessive proportions—as the molecule size decreases, the surface region increases.

The surface energy is significantly influenced by the expansion of a particle’s surface area. Modifications in the interparticle spacing or the separation between their constituent atoms are necessary. Incorporating nanoparticles enhances the surface adhesion and influences the voltammetric conductivity when deposited onto electrode surfaces. This results in an increased dynamic surface area, improved selectivity, the enhanced mass transport of reactants, and a better signal-to-noise ratio, among other enhancements. Due to their unique physicochemical properties, nanomaterials are particularly advantageous for electrochemical applications. Advances have been made in integrating mass transport mechanisms with nano-anodes to facilitate the investigation of electrochemical cycles. Previously unavailable at macroscopic scales, glass-like materials are now accessible at the nanoscale, leading to improved interactions and catalytic processes [54]. Additionally, nanosensor materials should exhibit durability and possess excellent dielectric strength. While nanosensors are inherently more delicate and diminutive, they may present a more cost-effective solution than conventional sensor types. Incorporating nanoparticles into a terminal results in two effects: (1) diminished detection probabilities and (2) enhanced reactivity, attributable to the increased surface area of nanostructured entities, thereby leading to a more extensive redox scale. Consequently, this results in augmented peak intensities. It is essential to emphasize that increased reactivity does not necessarily correlate with lower detection thresholds. In certain instances, the baseline noise levels may increase by an equivalent magnitude or even exceed the signal amplitude. This phenomenon is occasionally observed in modified carbon nanotube films. Meanwhile, (3) in situations where the signal amplification surpasses the noise levels, the detection limit can be improved; (4) they exhibit increased stability. These qualities allow for better reproducibility [54].

2.2. Advanced Materials for Electrodes

The configuration of universal or typical electrode materials, including graphite, smooth carbon, carbon filaments, deeply oriented pyrolytic graphite, and boron-doped diamond, has been augmented through the exploration of innovative carbonaceous substances [55,56,57,58,59]. Pencil graphite cathodes have emerged as substitutes for conventional anode materials owing to their advantageous electrical properties, economic viability, and potential for disposable applications [60]. Carbon-based interconnects, such as carbon particulates aggregated in a folio and carbon nanostructures utilizing surface engineering, remain subjects of investigation. These materials are frequently enhanced via the incorporation of electrocatalysts, redox mediators, or biorecognition elements, as biosensors facilitate improved detection capabilities. Recently, boron-doped diamond (BDD) has established an important position within materials science and engineering as a substrate with advanced performance. Fojta and his collaborators [61] gathered the latest advancements in BBD cathode applications, focusing on electrochemical processes involving biomolecules. The primary objective is to synthesize advanced films exhibiting superior BDD characteristics. This involves the modification of the BDD interfaces through the integration of diverse materials, including the incorporation of metallic particulates, the establishment of covalent linkages, and the assembly of metallic or metal oxide nanoparticles and nanorods at designated junctions. Techniques such as chemisorption and the formation of self-assembled monolayers (SAMs) are being investigated to engineer a robust biorecognition layer that mitigates contamination risks. Various methodologies are being explored to leverage nanostructured materials and judiciously select (bio)chemical agents to develop a specialized functional surface. This tailored surface may be employed for a multitude of applications. Sometimes, it is necessary to accept the costs associated with specific advantages, such as smaller windows, increased noise, lower resistance to passivation, and a shorter lifespan [62]. Immobilizing biorecognition elements on terminal surfaces is critical in advancing biosensor technology. Integrating relevant materials at these interfaces enhances the surface-to-volume ratio, significantly augmenting the analytical performance of the sensors. The research conducted by Trnkova has proposed various modification techniques, elucidating the advantageous characteristics of engineered layers composed of diverse terminal materials, tailored to amplified electrochemical DNA-based biosensors [63]. The capability to evaluate a broad spectrum of proteins across extensive concentration ranges holds considerable promise for multiplex disease diagnostics. An electrochemical ultrasensitive immunosensing platform was developed, utilizing human immunoglobulin G (HIgG) as the target analyte, featuring an oligonucleotide self-assembled monolayer that mediated the detection interface on a gold cathode. This design mitigates nonspecific adsorption and cross-reactivity while enabling the efficient modulation of the electrochemical signal [64,65,66]. Electrochemical nucleic acid biosensors are particularly significant in diagnostic applications, especially for the detection of specific DNA or RNA sequences associated with pathogens and viruses [67,68]. Thus, investigating the hybridization dynamics between an immobilized capture probe on the catalytic interface and the target nucleic acid within biological samples is essential. The electrochemical steric hindrance hybridization strategy demonstrates a low nanomolar detection limit, permitting the quantitative localization of larger biomolecules, such as antibodies, within 10 min.

Furthermore, printable electrodes represent a versatile material, commonly employed in fabricating point-of-care (POC) devices [69]. Screen-printing techniques continue to facilitate the cost-effective production of carbon paste, gold, and other screen-printed electrodes (SPEs) that exhibit heightened sensitivity and selectivity. The inherent simplicity of their integration with various devices paves the way for the development of disposable and user-friendly electrochemical platforms for health monitoring and continuous self-assessment [70]. The versatility of SPEs lies in their potential for chemical modification akin to traditional electrodes or even during the screen-printing process itself. Consequently, SPEs are promising candidates for the rapid screening of pharmaceuticals and biomolecules within complex matrices [71,72]. For instance, the work by Yamanaka et al. [73] has elucidated the fabrication and surface modification strategies of SPEs for the detection of specific DNA sequences, incorporating reverse transcription polymerase chain reactions (RT-PCR) for analytical applications.

2.3. Sensing Systems That Are Integrated into Both Paper and Textiles

Paper has consistently served as a substrate in fabricating paper-based analytical systems, enabling diverse methodologies for current detection and facilitating the differentiation of target biomolecules. This material is attractive and versatile and possesses a semi-normal structural composition, enhancing its utility in various scientific applications. The advancement of paper-based nanobiosensors has facilitated the early detection of immunological reactions and DNA/RNA hybridization events. Specific proteins can function as biotin–avidin or antigen–neutralizer conjugates, establishing a connection between the DNA/RNA molecules and the paper substrate. This interaction has been documented through various synthesis methods, design protocols, and applications [74,75,76,77,78,79,80]. The employment of inkjet [81], wax, and screen-printing technologies [82,83] has enabled the production of wearable biosensors suitable for in situ testing. These biosensors exhibit remarkable thermal stability across various temperatures and durations.

Innovative materials, such as Carnage TEX and other smart materials, including nylon, fleece, and cotton, have garnered significant attention due to their incorporation potential in devices for the monitoring of human fluids and tissue compositions. However, electrochemical biosensors often encounter challenges related to the non-conductivity of the materials. Therefore, integrating an additional conductive medium, a cathode, is essential in enhancing the material’s electrode surface. The ideal materials and filaments should not interfere with analyte signaling and exhibit biocompatibility for efficient sensor integration. A relatively limited number of publications have highlighted the applications of fiber-based electrochemical biosensors [84]. Due to its hydrophobic characteristics, test absorption resistance, high print fidelity, and ability to maintain electroactivity under strain, GORE-TEX has emerged as an excellent candidate for incorporation into electrochemical sensing devices [85]. The convergence of electrochemical sensors and nanomaterials is increasingly manifesting in clinical applications, progressing from laboratory-based research to practical deployment in clinical trials and pharmaceutical research and development. This evolution is driven by the significant demand for rapid, sensitive, and precise diagnostic methodologies. Nanotechnology-enhanced biosensors demonstrate significant potential across various medical fields, particularly in monitoring health statuses and disease diagnostics. For example, the amalgamation of electrochemical techniques and nanomaterials significantly enhances biosensors’ performance, facilitating the detection of specific biomarkers associated with diseases such as cancer and diabetes [3]. Early and accurate diagnosis is pivotal for effective therapeutic interventions and improved clinical outcomes.

Pharmaceutical enterprises, such as Abbott and Medtronic, have pioneered biosensors embodying this transformative trend. Abbott’s continuous glucose monitoring systems utilize electrochemical sensors to deliver real-time glucose measurements, which is critical for diabetes management. These sensors have undergone stringent validation protocols within clinical environments to ensure their reliability and precision, rendering them appropriate for patient utilization [11]. Likewise, Medtronic has developed implantable sensors capable of monitoring various physiological parameters. These devices exploit nanomaterials to enhance their sensitivity and biocompatibility, effectively addressing the challenges associated with prolonged implantation periods. The validation of these technologies in clinical settings demands extensive trials to substantiate their efficacy and safety, ultimately culminating in regulatory approvals for broad-based applications. The integration of electrochemical sensors and nanomaterials into clinical frameworks represents a noteworthy advancement in medical technology [21]. Continuous collaboration between researchers and pharmaceutical entities is pivotal in refining these innovations and ensuring their successful transition from laboratory settings to clinical utilization.

2.4. Self-Propelled Micro- and Nanomachines

Miniature and nanomotors (MNMs) have achieved considerable prominence as remarkably sophisticated mechanistic devices and vehicles in the last decade [86,87,88,89,90]. They find application in numerous high-stakes scientific domains. Exhibiting an extensive array of exceptional mechanical properties, MNMs facilitate a range of dynamic functionalities, including rotation, rolling, transportation, delivery, contraction, and collective motion, rendering them highly adaptable for intricate detection systems. The construction of MNMs typically involves foundational materials, which are often fabricated from silicon-based substrates [91], polymers [92,93,94], or noble and various metals [95]. The self-propulsion phenomenon driven by gradients from adjacent electrochemical reactions is an intriguing mechanism for independent movement [96]. Utilizing specific responsive materials is paramount for the efficacy of the determination system. These materials facilitate the transmutation of the compound energy generated by forces, particularly hydrogen peroxide, into kinetic energy, propelling molecular nanomachines forward. This propulsion is essential in achieving the particular material’s synthesis of the MNM surface, including various synergistic materials employed [97]. Merkoçi’s consortium [98] has elucidated advancements in micro-/nanomotor science and technology, concentrating on elucidating the motion dynamics, exploring novel energy sources, and developing such motors with bioactive molecules as surface modifiers, predominantly tailored to analytical applications. For prospective biotechnological implementations, the organization of self-propelling nano- and micromotors leveraging Janus architectures is particularly compelling [99]. Notably, these nanomotors show promise in the delivery of chemotherapeutic agents, such as Tamoxifen [100]. Self-propelled micro-nanoscale machines present numerous benefits due to being ecologically benign, mainly through their remarkably efficient conversion of chemical energy into mechanical energy. This transformation employs non-toxic energy sources and external stimuli, such as photonic inputs, as an abundant, controllable, and zero-waste propulsion medium. Consolidating such properties with valuable materials and promoting their practical application would lead to an increase in the use of long-lifetime (bio)sensing frameworks.

2.5. Self-Powered Biofuel Cells

Biofuel cells (BFCs) have recently emerged as a novel analytical platform, harnessing naturally dynamic biomolecules, primarily proteins [101]. BFCs provide a distinctive and autonomous biosensing mechanism, diverging from the conventional methodologies employed in the fabrication of electrochemical biosensors. This innovative system proficiently transduces the stored chemical energy inherent in biomolecules into electrochemical energy, facilitating advanced biosensing applications. This aspect enhances their functionality in fabricating wearable and adaptable sensing devices for the self-monitoring of health parameters, as many developed biosenors are contingent upon an energy source. Thus, either an electromagnetic field or a non-recyclable lithium battery is needed [102]. Modified electrodes have been proposed for the detection of lactate [103], oxygen, and glucose [104,105], as well as the initial phase of malignant growth [106] in human physiological liquids [107]. These electrical frameworks offer remarkable potential for future research and biomedical applications because of their unique biological nature, which makes them appealing for in vivo testing [108].

2.6. Regulatory Standards and Current Challenges

For FDA approval, medical sensors must undergo extensive clinical testing to ensure their accuracy, reliability, reproducibility, and safety. Electrochemical sensors for drug detection face challenges due to the need for high precision at low analyte concentrations. The FDA typically requires multiple phases of clinical trials, including robust double-blind studies, to assess effectiveness compared to established methods. These sensors must also demonstrate stability, biocompatibility, and repeatability, which can be complex due to the variability in nanomaterials. While these sensors show promise, achieving consistent reproducibility and accuracy across diverse patient populations remains difficult. Factors like enzyme degradation and interference from biological matrices can affect readings. Additionally, clinical trials require large sample sizes and lengthy testing, increasing the development costs. Companies like Abbott and Medtronic, known for their successful glucose monitoring biosensors, have navigated these regulatory demands through rigorous testing. For instance, Abbott’s FreeStyle Libre and Medtronic’s glucose sensors met the FDA standards by demonstrating sustained accuracy in extensive clinical trials, followed by ongoing post-market surveillance [87]. The future of electrochemical sensors in drug detection may involve advancements in nanomaterial stability and integration with digital health systems. Regulatory bodies are increasingly open to innovative technologies, such as the FDA’s Breakthrough Devices Program, which could expedite the approval of promising sensor technologies that demonstrate significant clinical benefits.

3. Nanomaterials for Electrochemical Sensing

The integration of nanomaterials has allowed novel and viable detection platforms to be created. This section covers a few significant nanomaterials and nanocomposites, generally utilized to plan the advanced execution of electrochemical sensors and biosensors to distinguish drug compounds (Figure 2).

3.1. Carbon-Based Nanomaterials

In contrast to many other nanomaterials, carbon-based materials have a few unique advantages. They exhibit large surface-to-volume ratios, increased mechanical strength, strong electrical conductivity, and long-range material solidity [109]. Due to these qualities, carbon-based nanomaterials can have greater awareness and lower recognition limits. They are frequently also suitable as supports for surface chemistry with aptamers, pharmaceuticals, and other nanomaterials.

3.1.1. Carbon Nanotubes

Due to their superior conductivity and outstanding processability, carbon nanotubes (CNTs) are increasingly preferred for electrochemical devices. Contingent upon the particular atomic design and synthetic creation of drugs, CNTs might be utilized to advance electron movement in numerous responses and work with the adsorption of natural particles. Additionally, CNTs can serve as platforms for new device fabrication [110,111,112,113,114,115,116,117,118]. Their strong conductivity and large surface-to-volume ratio can increase the surface-level presentation of driving factors. Moreover, CNTs might deliver synergetic outcomes that advance detection. SWCNTs, or single-walled carbon nanotubes, are cylindrical tubes with a single graphene sheet and a wall thickness ranging from 0.4 to 2.5 nm. The tiny size and three-dimensionality of nanoparticles can enhance the energy of electron transport in many ways, in addition to their high electrical conductivity.

Their enormous surface-to-volume ratios may have a considerable impact on the overall signal-to-noise percentages. The fact that the nanotubes’ constituent parts can be adjusted to enhance the desired response is crucial. For instance, Bandyopadhyay et al. described how they could successfully intercalate or trap harmful insect sprays by changing the SWCNTs’ spans, enhancing the particles’ electrochemical oxidation [119]. With varying widths of up to 100 nm, MWCNTs are incorporated into various settling graphene sheet layers. MWCNTs have large surface-to-volume ratios, excellent conductivity, and profound tunability, much like SWCNTs. Nevertheless, while constructing electrochemical sensors, significant distinctions between SWCNTs and MWCNTs must also be considered [120]. MWCNTs are relatively rigid, but SWCNTs are typically more flexible. Likewise, the development of SWCNTs requires more resources and is often more costly.

3.1.2. Graphene and Graphene Oxide

Graphene is a hexagonal sheet of sp²-hybridized carbon, known for its exceptional electrical and structural properties. It is valuable for phase determination and electrochemical detection [121]. While the beneficial oxygen groups in graphene oxide (GO) can enhance the detection of specific analytes, their presence often reduces the surface conductivity [122]. Interestingly, these oxygen functional groups can be intentionally reduced through electrochemical or thermal methods, potentially leading to defects like monovacancies, which can significantly accelerate the catalysis of various atoms. Additionally, doping graphene with heteroatoms can activate surface charges, creating synergistic sites for different particles and aiding in electrostatic interactions [123,124,125,126,127,128].

Like carbon nanotubes (CNTs), graphene-based nanostructures can serve as frameworks for further derivatization. Preserved nanoparticles (NPs) can be balanced with graphene and GO materials, preventing aggregation and enhancing the performance [129]. The large specific surface area, carrier mobility, and electrical conductivity of graphene allow for the development of low-cost electrode materials that boost the sensitivity and selectivity of electrochemical sensors. The rapid electron transfer facilitated by graphene lowers the activation energy for reactions, improving the overall kinetics of detection [130].

Furthermore, the unique properties of graphene enable the formation of various nanocomposites, optimizing sensors’ performance through enhanced electrochemical responses [122]. Functionalization with oxygenated groups increases the hydrophilicity, promoting better interaction with analytes. This is essential in achieving lower detection limits and faster response times. Overall, integrating graphene into sensor technology improves the electrochemical detection process and contributes to the creation of highly efficient biosensing platforms for diverse applications [128,129].

3.2. Noble Metal Nanomaterials

Because of their excellent reactant capacities, large reactant sizes, and diverse forms, MNs are frequently applied for the detection of pharmacological analytes. Through the careful planning of their surfaces and application circumstances, utilizing coating materials and supramolecular interactions, which play a crucial role in the production of nanoparticles, it is possible to manage the nanoparticles’ sizes, forms, and characteristics [131]. The size, adsorption power, orientation, and substantial components of the molecules all play a role in identifying nanoparticles for a given analyte. To improve reactant detection, bi- or trimetallic NPs can be used for synergistic effects. Examples include the edge locations of cucurbituril groups or the interiors or exteriors of cyclodextrin rings [132]. As detection platforms, various three-dimensional (3D) nanomaterials, such as those containing nanopores, blank forms, and circles, might be used [133]. Since the compounds may have synergistic effects, bi- and trimetallic composites occasionally enhance the detection power. The alteration of intermediates, improvements in analyte adsorption, proton movement, and reduction in the energizing barrier of the interactions between the analytes and the composite may be attributed to the synergetic effects of different metals [134].

3.3. Metal–Carbon Nanocomposites

Metal–carbon matrix composites have primarily been studied for detection because of their high conductance, huge surface areas, and affordable prices. Nanoparticles can adhere to the vast surface areas of carbon nanomaterials, increasing the population in sensitive regions. Combining materials based on graphene commonly results in blended metal oxides and metal nanoparticles. In particular, GO can decrease particle agglomeration and resolve it, thanks to graphene/GO–metal nanoparticle nanocomposites.

3.4. TiO₂-Supported Nanomaterials

Due to their substance persistence and low cytotoxicity, TiO₂-supported nanostructures are frequently utilized in electrochemical detection. They have outstanding photosynergetic capabilities and adaptability. When TiO₂ nanorods or nanotubes are ornamented with metal nanoparticles, for example, the well-known features of numerous materials might be utilized. To reduce the possibility of coupling among electron transporters and side reactions, the conductivity and charge movement are enhanced by the nanoparticles’ dynamic nature, rather than by the TiO₂ support material. Ti also has the advantage of being a biocompatible substance, making it particularly suitable for biomedical applications. Ti is often plentiful, reducing the production costs compared to products with noble metals. TiO₂ can also be considered in more severe circumstances when the electrochemical sensor and nanomaterial are joined and active [135,136,137,138,139].

3.5. Conductive Polymers

Conducive polymers have been included in composites for detection applications over the past ten years. Because of their intriguing behavior when exposed to the electroactive properties of the applied electric field, especially their conductance, conductive polymers are promising [140]. Most of the atoms in these polymers originate from nature. Conductive polymers can improve the discrimination and susceptibility of sensors for specific analytes. Due to their ability to strengthen the particular series of connections between the detection point and the analyte, atomically engraved polymer (MIP) composites have recently attracted attention. These composites are particularly helpful in identifying analytes in complex organic lattices, where selectivity and fouling are significant problems [141]. Furthermore, because MIPs are typically much less expensive than natural transducers, they offer superior practicality and reusability compared to organic receptors. By restricting target atoms, MIPs may also operate as signal transducers that alter the mass, absorption coefficient, absorptivity, conductivity, electric potential, and movement. The development of MIPs is typically supported by computational screening approaches, explaining how possible MIP–analyte interactions work. Additionally, adding MIPs to carbon or metal materials may make the resulting electrochemical sensors more sensitive.

4. Drug Detection Using Electrochemical Sensors and Biosensors

Sensors have been developed for the recognition of numerous types of essential medications. However, due to the underlying medical structures, these sensors frequently require explicit connection points to exploit their tremendous potential for recognition. New electrochemical sensors are being continuously developed to improve their awareness and power and address identification limits. Based on their traits, they can be divided into six distinct groups of clinical applications and properties. These categories include calming, energizing, antibacterial, parasitic, viral, and malignant growth.

4.1. Anti-Inflammatory Drugs

Inflammation is treated with nonsteroidal anti-inflammatory drugs (NSAIDs), which also lessen discomfort, itching, and heat. NSAIDs and painkillers can be used to treat various ailments, making them important medical treatments. When they were identified in the middle of the 19th century, which made it possible to synthesize these substances, this led to the creation of the acetylsalicylic acid or aspirin. NSAIDs, the majority of which are organic acids, were also created due to the chemical discoveries of the 19th and 20th centuries. Following World War II, NSAIDs were first discovered during the pre-prostaglandin era, prior to the 1970s; then, during the later half of the 20th century, the drug discovery process included testing for their impacts on production. Among their physiological functions are those related to the gastrointestinal system, the kidneys, the vascular system, and various other organs. Prostaglandins (PGs) and thromboxane (TxA2) are prostanoids. Two cyclo-oxygenases (COX) control prostanoid production: COX-1 produces PGs and TxA2, which regulates inflammation, pain, and fever, and COX-2 produces prostanoids. COX-2-specific medications were developed in the 1990s to limit COX-2 and spare COX-1; these play a significant role in physiological functioning and are thought to play an essential role in the emergence of adverse reactions, especially those involving the gastrointestinal (GI) tract. Despite the introduction of two new COX-2 inhibitors, which were promoted as having low GI side effects, there was a tremendous amount of commercial development at the turn of the century. In addition to arthritis and pain, COX isoforms have been implicated in several non-arthritic and non-pain-related diseases with inflammation within their etiology, such as cancer, Alzheimer’s disease, and other neurodegenerative conditions. The utilization of novel drug delivery technologies for NSAIDs and, to a lesser extent, safer applications of corticosteroids are more recent technological advancements, occurring in the twenty-first century. Moreover, the drowsiness caused by medications like acetaminophen is not very strong. NSAIDs are generally available without a prescription; thus, they are possibly the most poorly handled pharmaceuticals. Consumers’ widespread use of NSAIDs has resulted in severe issues with water pollution [142]. Because cyclooxygenase (COX-1 or COX-2) helps to produce prostaglandins, it is implicated in the aggravation and flagging cycle, and all NSAIDs operate by blocking their movement [143].

4.1.1. Naproxen

Ibuprofen and naproxen, two of the most well-known NSAIDs, are propanoic acid subordinates that independently have one and two benzene rings in their synthetic compositions. Both isoniazid and naproxen undergo electrochemical oxidation; typically, a one-electron move causes fast oxidation after the decarboxylation event to create a liquid subsidiary to the material [144]. Shokri et al. examined the impact of fluorescence probe for detection of naproxen in pharmaceutical formulations and water samples using MPA-capped CdTe/ZnS core-shell nanocrystal-neutral red [145]. The increase in fluorescence intensity displayed a direct correlation with the concentration of naproxen, adhering to a linear pattern within the concentration range of 2.00 × 10⁻¹ to 27.3 µmol/L, with detection limits established at 7.0 × 10⁻² µmol/L. A disposable electrochemical sensor (AgNPs@GO-Cd) was developed, composed of a computerized circular chip holding gold and altered by silver nanoparticles [146]. The produced terminals demonstrated their value and potential for numerous applications by recognizing naproxen pills and naproxen in human urine tests. Enzymatic electrochemical sensors are usually used to identify biological species, since they are precise, and their practical applications are supported by real-world evidence. Specific proteins of interest are combined with nanoparticles to settle the chemicals and enhance sensors’ responses. A cytochrome-P450-based electrochemical sensor was used by Rossi et al. to develop an amperometric biosensor that could detect naproxen by dropping microsomal P4501A2 (msCYP1A2) and MWCNTs onto a screen-printed electrode for graphite (SPE) [147]. A tiny commercial osmotic siphon was used to examine drug transport, and this electrochemical sensor was shown to have a slightly better LOD than other approaches.

Alagumalai et al. [148] studied naproxen electrooxidation using a noble metal efficiently doped on oxidized SWCNTs with GO on its surface. Using the ultrasound-assisted sonication technique, a hybrid nanocomposite, Au@f-CNT/GO, was created and used to accurately quantify the medication NPZ. The proposed sensor also exhibited excellent selectivity, stability, reproducibility, and repeatability. Further evidence that the recommended sensor may be helpful in accurately detecting NPZ in various water and biological samples was derived from an accurate sample analysis.

Díaz et al. [149] investigated the degradation of naproxen using CV and three different MWCNT working electrodes (MWCNT, MWCNT-COOH, and MWCNT-NH₂). The process of electrochemical oxidation results in two peaks that align with the oxidation of deprotonated NPX, which is followed by decarboxylation and additional electron transfer oxidation. The highest removal efficiency, which was 82.5%, was achieved at a constant potential of +1.5 V after a duration of 20 hours at 500 rpm.

Kanagasabapathy et al. [150] used peroxide to aid the electrochemical oxidation process of nano-spinel zinc ferrite films (ZFO). The films’ shapes, textures, and electrochemical properties, as well as their lattice structures, were investigated. It was determined that the anodic oxidation and oxyhydroxide deposition electrochemical kinetics were quasi-reversible. Through electropolymerization, Hung et al. [151] produced a poly(L-serine)-modified glassy carbon electrode (PLS/GCE) to investigate naproxen detection. A calibration curve for linear sweep voltammetry was created in the concentration range of 4.3–65 μM, corresponding to a detection limit and standard retrieval of 0.69 μM and 104 ± 2.5%, respectively (Figure 3).

A CPE modified with carbon nanofibers (CNFs), gold nanoparticles (Au), and polyaniline was used by Afzali et al. [152] to conduct a voltammetric analysis of naproxen. The ionic compound Bmim[PF₆], which has a butyl-3-methylimidazolium and hexafluorophosphate anion, could be used as an electrode modifier.

4.1.2. Ibuprofen

To create the ultrasensitive electrochemical sensor described by Roushani et al. for the discovery of ibuprofen, a covalent bond between an aptamer and gold nanoparticles was formed on a polished carbon terminal (GCE) surface. Ibuprofen’s oxidation was aided by adding AuNPs, which enhanced the active surface area. The aptamer improved the analyte reaction’s signal-to-noise ratio and the sensor’s selectivity and awareness. In this system, a static self-assembled monolayer (SAM) was created using cysteamine, and terephthalate was used as the connecting agent to covalently bond an ibuprofen-explicit aptamer (ssDNA2) to the AuNP/GCE surface [153]. Stable SAMs were created by functionalizing AuNPs stored on the GCE with cysteine. The addition of terephthalate and a 3′-amine-ended catch test came next (ssDNA1). Because the ibuprofen compound covered the terminal’s surface and impeded the electron’s mobility with the redox species, the current decreased as the analyte’s centralization increased. Nair et al. also created an AgNP-modified, acid-functionalized GO electrochemical sensor for naproxen that was wrapped in a polymer. Compared to a GO-only sensor, this sensor demonstrated enhanced responsiveness and a lower detection limit [154]. Electrochemical sensors have shown significant promise in detecting and quantifying ibuprofen in pharmaceutical formulations, clinical samples, and environmental monitoring. They can reliably quantify ibuprofen, which is crucial for real-time patient monitoring and quality control, achieving excellent recovery rates above 95%. These sensors also addressed concerns about pharmaceutical contamination in water systems by detecting ibuprofen at concentrations as low as several parts per billion (ppb). Their high sensitivity and selectivity make them valuable for the monitoring of pharmaceutical contamination and in ensuring safety and efficacy across various applications.

Mutharani et al. [155] created an electrochemical sensor for the detection of the anti-inflammatory medication ibuprofen (IBU) in human body fluids, which was studied. It was verified through the facile wet-chemical synthesis of 3D copper tellurate (Cu₃TeO₆), a powerful electrocatalyst. Different methods were used to characterize the synthesized Cu₃TeO₆. The dynamic detection range for the electrochemical determination of IBU was 0.02–5 M and 9–246 M, respectively (Figure 4). Because of its properties, ibuprofen is a frequently recommended medication. In sensor and medication delivery systems, fullerenes and carbon nanotubes were studied as innovative components by Parlak et al. [156]. It was discovered that SiC59 strongly interacted with IBU and had higher electrical sensitivity than the Si@SWCNT system.

4.1.3. Aspirin

Painkillers are acetylated salicylates with benzene rings and carboxylic groups, which are analogous to propionic acids. Ibuprofen is hydrolyzed into salicylic acid during the oxidation of headache medications. Salicylic acid is exposed to a one-electron deficit to form a free radical. The radical is converted to 2,5-dihydroxybenzoic acid through the combination of another radical and the loss of an electron [157]. Poly-4-vinylpyridine (P4VP) was found to be folded over MWCNTs and drop-projected onto a GCE surface, according to Ghadimi et al. According to the research in [158], joining conductive polymers affects the compound’s conductivity, electron transport energy, and electrocatalytic action. Diouf et al. published a paper on an electrochemical sensor composed of self-collecting chitosan wrapped in AuNPs on a screen-printed carbon cathode (SPCE). The chitosan was electrically protective, while showing excellent synergistic movement for anti-inflammatory drugs. To overcome this, AuNPs were combined, increasing the conductivity and promoting catalytic activity. Because of their significant synergistic properties, large surface-to-volume ratio, and high conductivity, AuNPs are frequently used to detect analytes. Through DPV, this fabricated sensor achieved an LOD of 0.03 ng/L [159].

The interest in creating pharmacological diagnostics techniques has recently increased due to the rise in inflammatory illnesses. When taken in therapeutic doses, acetylsalicylic acid (ASA or aspirin) can be used to treat several diseases. However, ASA overdoses can cause adverse side effects, such as ulcers and gastrointestinal damage. This makes it perfect for the development of sensitive, rapid, and portable ASA detection techniques. Diouf et al. [159] used an electrochemical sensor and an electronic voltammeter to analyze aspirin levels in urine, saliva, and a medication tablet. The electrochemical sensor was self-assembled on a screen-printed carbon electrode (SPCE) with chitosan-coated gold nanoparticles. From the data for both devices, prediction models were created using the partial least squares (PLS) method, which produced a regression correlation coefficient R² = 0.99. As shown in Figure 5, both the VE-Tongue and the SPCE/(Cs + AuNPs) electrochemical sensors may offer practical tools for the examination of the biological effects of drugs.

Xia et al. created a new indium (In)-doped PbO₂ electrode for the electrochemical degradation of refractory organic contaminants using the electrodeposition process [160]. After doping, there were energy savings of up to 30.56%. This finding matched the surface characterization data of PbO₂ electrodes quite well.

4.1.4. Diclofenac and Celecoxib

Diclofenac is a non-steroidal anti-inflammatory medicine that is widely used worldwide to treat various illnesses, including osteoarthritis, ankylosing spondylitis, and ailments that cause severe muscle pain. Diclofenac has no side effects when taken in the recommended amounts, but an overdose can negatively affect the body [161]. Additionally, even trace amounts of diclofenac in ecosystems harm the health of living things. As a result, it is necessary to create analytical methods for diclofenac monitoring. Biosensing and electrochemical sensing techniques have been widely described in this field.

Diclofenac and indomethacin play a role in gathering NSAID residues, although they are less common than ibuprofen, headache medicines, and naproxen. Sataraddi et al. effectively utilized an MWCNT-modified GCE for the electrochemical detection of indomethacin, which was used to verify the precision of commercial drug tests and identify diclofenac in complex human liquids [162]. The diclofenac particle is divided through the nitrogen molecule during electrochemical oxidation. The one-electron irreversible oxidation process is part of the electrochemical oxidation process. Celecoxib, a less popular NSAID, lessens discomfort by inhibiting COX-2, the enzyme that starts inflammatory responses. Arkan et al. [163] illustrated a graphene–gold nanocomposite carbon ionic fluid cathode to select celecoxib. The graphene and gold nanoparticles demonstrated superior interactions compared to the electrochemical sensor.

Shalauddin et al. [164] presented the electrochemical detection of acetaminophen and diclofenac sodium using a nanocomposite composed of nanocellulose (NC), functionalized multiwalled carbon nanotubes (fMWCNTs), and biosynthesized copper nanoparticles (CuN) (NC-fMWCNT-CuN/GCE). Green tea leaf extract was used as a reducing and stabilizing agent in the biosynthesized CuN process for the first time. The SWV approach was used to perform the simultaneous determination. The substantial recoveries and low RSDs show the sensor’s potential for use in accurate sample detection. It offers a potential sensing platform for the detection of pharmaceutical formulations in human blood and serum.

Honakeri et al. [165] developed a novel core–shell nanostructure-modified sensor based on carbon electrodes, demonstrating improved sensitivity towards diclofenac. A discrete voltammetric technique was used to determine diclofenac’s electrochemical behavior and applications (DCF). According to the proposed modified electrode, DCF was electrooxidized and electrocatalyzed strongly compared to the bare electrode, with a higher peak shift. In addition to being fast, consistent, repeatable, and reproducible, the modified electrode possessed other unique qualities. The authors considered how different performance parameters affected the peak improvement. The limit of quantification (LOQ) was determined at 11.3 × 10⁻⁸ M, and the limit of detection (LOD) was 3.41 × 10⁻⁸ M. The relevance of the proposed scheme was assessed by analyzing DCF in drug products and human samples. The DCF recovery in the tablet reached 97.5%, with an RSD of 0.7%.

4.2. Antidepressants

Antidepressants may currently rank among the most abused and widely prescribed drugs. Most antidepressants disrupt sleep—namely, the physiological patterns of the several stages of sleep, which can be monitored overnight using EEG and other physiological markers. The most effective antidepressants for rapid eye movement (REM) sleep are those that improve serotonin activity by slowing metabolism or preventing reuptake. Early in treatment, the reduction in REM sleep seems to be the greatest. However, after the use of monoamine oxidase drugs, when REM sleep is frequently absent for several months, it steadily decreases after long-term medication use. Antidepressants can impact sleep onset and maintenance, but the effects vary considerably among medications. Early in treatment, some antidepressants—including clomipramine and SSRIs, particularly fluoxetine—are sleep-disturbing, whereas others, including amitriptyline and the more recent serotonin 5-HT2-receptor antagonists, promote sleep. After a few weeks of treatment, these effects are comparatively fleeting, and there are not many noticeable distinctions among such medicines. In general, within the first 3–4 weeks of the use of some effective antidepressant treatments, depressed patients’ objectively measured sleep and subjective sleep quality was improved. When insomnia is bothersome, or to ensure compliance, improving sleep early in therapy may be an essential clinical aim for some patients. In these patients, it is advised to choose an antidepressant that is well tolerated and effective and enhances short-term sleep. Before selecting a course of treatment, it is essential to rule out other sleep problems in patients, such as REM sleep behavior disorders and restless leg syndrome, which some antidepressants can exacerbate. On the other hand, there is proof that some antidepressants may help with sleep disturbances, including anxiety attacks.

Dopamine, norepinephrine, and serotonin—the three types of monoamines—serve as synapses at which signals are sent to the cerebrum’s nerve receptors. For individuals who experience depression or other mental health issues, antidepressants work by enhancing the effects of these synapses. There are five different classes of antidepressants, but selective serotonin reuptake inhibitors (SSRIs), which prevent serotonin reuptake, are the most well-known class. The three most well-known types, paroxetine (Paxil), fluoxetine (Prozac), and sertraline (Zoloft), are typically larger, making their electrochemical oxidation more challenging. Because of this, contrary to NSAIDs and medications from all other classes, these medicines are manufactured with fewer electrochemical sensors.

4.2.1. Fluoxetine

MIP NPs with fluoxetine (combined by precipitation polymerization) were recently included in a CPE [166]. The coordinated terminal’s graphene significantly increased the awareness. A fluoxetine-engraved polymer was created using methacrylic acid and vinyl benzene (VB). The former provides hydrogen-bonding interactions with fluoxetine using its alternative amine and fluorine groups. By analyzing different strategies, the inclusion of graphene to increase the conductivity was considered. Two techniques for the consolidation of graphene were used with nano-MIP-modified carbon glue anodes. The subsequent method (nano-MIP/G2-CP) combined graphene with an orchestrated polymer, instead of the original method’s combination of graphene, graphite, and MIP powder. The nano-MIP/G2-CP produced the best results. The cathode demonstrated excellent responsiveness while revealing an LOD of 2.8 nM. Ardelean et al. developed a carbon nanofiber–epoxy composite cathode for fluoxetine, and antibiotics were detected electrochemically in water simultaneously [167].

The demand for healthy products that aid in weight loss is rising due to the global obesity pandemic. However, unstated adulterants are frequently added to improve their performance, and the creation of quick procedures for the identification of these substances is crucial. Ramos et al. [168] showed that the doping agent fluoxetine could be quickly detected and quantified in samples with boron-doped diamond as the working electrode. After simple sample dilution in a supportive electrolyte solution, quick fluoxetine screening is feasible. These findings imply that the technique has much potential as a quick and easy screening test to detect FLU in natural items used in obesity treatment.

4.2.2. Paroxetine

Another SSRI that is widely used to treat severe anxiety problems is paroxetine, marketed under the trade name Paxil and comparable to other SSRIs [169]. Oghli et al. demonstrated a polyoxometalate/diminished graphene oxide (rGO)-modified pencil graphite sensor after subsequently identifying paroxetine [170]. Pencil graphite anodes (PGEs) offer an advantage over other carbon-based cathodes because of their inexpensive costs, excellent mechanical dependability, low foundation currents, and wide anticipated window. A small portion of the graphite cathode surface had to be removed to eliminate memory effects and the adsorbed species that caused terminal fouling. The rGO was combined with the proton-moving phosphotungstic acid, which was then used to modify the PGE. The electrochemical sensor performed flawlessly to break down paroxetine in serum and urine.

4.2.3. Sertraline

Another well-known SSRI is sertraline, which is marketed as Zoloft. Khosrokhavar et al. [171] created a graphene nanosheet for sertraline that consolidated an MIP as an SPCE. The electrocatalyst for the identification of sertraline was a Ni–levodopa film bound to AuNPs, and, in the modified GCE, AuNPs and MWCNTs cooperated in providing a substantial surface area that could electropolymerize more Ni(II)-LD, leading to the increased electrochemical oxidation of sertraline. In a study by Shoja et al. [172], the use of Ni(II)-Ni(III) redox couples along with levodopa was proven to have a strong synergist effect for the oxidation of natural components like amines, carboxylic groups, and alcohols. Based on estimations of this system’s reliability, sertraline could undergo electrochemical oxidation consisting of two electrons and two protons.

4.2.4. Venlafaxine

SNRIs, or serotonin and norepinephrine reuptake inhibitors, are a unique class of antidepressants. SNRIs are more effective than SSRIs in alleviating more severe anxiety [173]. Iron oxide (Fe₃O₄) has become a sought-after electrocatalyst for the oxidation of natural particles and detection of organic molecules [174]. To differentiate between venlafaxine and venlafaxine, Khalilzadeh et al. created an electrochemical sensor with iron oxide nanoparticles stored on a cellulose nanocrystal–copper nanocomposite (Fe₃O₄@CNC/Cu) [175]. Petasites hybridus leaf was used to develop electrocatalysts and served as a copper settler. This cycle could continue spontaneously [175]. The creators of the proposed electrical detector used DPV to analyze venlafaxine quantitatively in samples; Figure 4c shows the DPV bending. The electrochemical sensor showed acceptable responsiveness and a wide range, with a lower detection limit than in other literature reports.

4.2.5. TCAs

Tricyclic antidepressants (TCAs), among the first antidepressants that were widely recommended in the 1950s, continue to be a popular option [176]. A nitrogen molecule is consolidated in their design’s focal ring, consisting of three freely measured connected rings. Additionally, TCAs can prevent neuroreceptors from reabsorbing serotonin, norepinephrine, and acetylcholine. To detect imipramine, Jankowska-Sliwinska et al. developed a DNA-based electrochemical sensor. Using oligonucleotide successions and their integral strands that had been thiol-marked, electrochemical sensors for gold glue were tuned. Unexpectedly, the DNA-adjusted sensor outperformed an exposed gold adhesive and DNA terminals [177]. A simple one-pot sonochemical synthesis method was used to create a bismuth oxide nano-tile-enhanced peeling graphite terminal, which demonstrated a respectable detection range (0.02–82.3 µM) and a feasible detection limit (6 nM) for imipramine [178]. While SPEs and fine carbon in natural grids demonstrated great results in experiments with desipramine [179], an improved electrochemical sensor, composed of palladium nanoparticle-brightened rGO, showed promise in assessing the amount of imipramine in human urine [180]. According to adsorptive stripping voltammetry, Sanghavi and Srivastava [181] simultaneously identified imipramine, trimipramine, and desipramine, when adopting titanium dioxide with an Amberlite XAD-2-modified CPE.

4.3. Antibacterial Medications

Antibacterial drugs (antitoxins) are generally utilized to treat bacterial infections in humans, animals, and plants. These medications are broadly used given the diverse distribution of microbes through different systems. Their activity follows four distinct pathways, including the inhibition of chemicals in cell wall amalgamation, nucleic acid digestion, protein combination, and cell film disturbance. Bacteria are targeted by antibiotics, which belong to the class of antimicrobial agents. Due to the effectiveness of antibiotics in treating and preventing bacterial infections, they are frequently used in this field. The growth of bacteria can be suppressed or terminated. Only a small number of antibiotics also have antiprotozoal qualities. In contrast to antibiotics, which are ineffective against viruses like the flu or the common cold, antiviral drugs or antivirals are pharmaceuticals that prevent the growth of viruses. The word “antibiotic”, which means “opposing life”, is derived from the Greek words “anti”, which means “against”, and “bios”, which means “life”, and is used to refer to any medication intended to target bacteria. However, in standard medical practice, only naturally occurring antibiotics (like penicillin) are used (by one microorganism fighting another). Sulfonamides and antiseptics are examples of non-antibiotic antibacterials that are entirely manufactured. However, both types are included in antimicrobial chemotherapy and have the same goal of destroying or limiting bacterial growth. In contrast to antibiotics, a substantial number of antibacterials are utilized in medicine and, on occasion, in animal feed. “Antibacterials” include antiseptic drugs, antibacterial soaps, and chemical disinfectants. Antibiotics have been used since the beginning of time. The therapeutic value of moldy bread has been mentioned in Ancient Egypt, Nubia, China, Serbia, Greece, and Rome, among other cultures. The earliest formal record of the use of mold to treat ailments was created by John Parkinson (1567–1650). In the 20th century, antibiotics changed medicine. Modern penicillin was discovered in 1928 by Alexander Fleming (1881–1955), and its widespread use was beneficial throughout the war. However, because antibiotics are so powerful and accessible, certain bacteria have developed resistance to them due to abuse.

As anti-infection agents have gained increased interest as a solution for an expansive range of illnesses, from rankles to tuberculosis, the development of anti-infection agents and their misuse have increased. Because of the unreasonable use of antimicrobials for various conditions, microorganisms have developed resistance to these medications. These resistant bacterial strains increase the spread of viral diseases, which necessitates frequent monitoring among patients. Excess consumption can trigger numerous detrimental side effects, like sensitivities, bone marrow damage, cancer, nephropathy, immunopathological effects, hepatoxicity, and regenerative problems. To achieve the close monitoring of these medications to limit the adverse consequences for the climate and general human well-being, further developments should be made in light of new advancements and materials. These medications can be ordered by their structures and chiefly include sulfonamide (sulfamethizole), macrolides (erythromycin), antibiotic medications (oxytetracycline), fluoroquinolones (ciprofloxacin), and β-lactam (penicillin). The electrochemical identification of some of these basic antimicrobials is examined below.

4.3.1. Penicillin

The antitoxin penicillin is most frequently used to treat staphylococcal and streptococcal infections. The catalysts trapped on crossover Pt-nanowire/Au-NP clusters displayed high responsiveness for the identification of penicillin and antibiotic medications, according to an electrochemical detection platform designed for the oxidation of penicillin to penicillin acid, with the arrival of carbon dioxide within sight of the penicillinase catalyst, as shown in Figure 6 [182]. Most electrochemical identification techniques focus on a few distinct types of penicillin [183]. Feier and colleagues investigated the electrochemical behaviors of each of the five penicillin types with a boron-doped precious stone terminal (BDDE). This demonstrated that this group of drug particles can likely be highly oxidized [184]. With a detection limit of 57 ng/L when recognizing penicillin, a GCE modified with graphene, poly(3,4-ethylenedioxythiophene (PEDOT), and AuNPs displayed excellent responsiveness [185]. The interaction of Printex 6L Carbon (P6LC) and CdTe quantum dots (QDs) inside a PEDOT, namely poly(3,4-ethylenedioxythiophene)-poly(styrene sulfonate) (PSS) film, enabled the creation of another electrochemical sensor for the detection of amoxicillin (AMX) [186]. A gold sign transducer was used to demonstrate the electrochemical detection of penicillin G in milk, which revealed a detection limit of 2 μM [187]. This research focused on distinguishing penicillin G from other types of penicillin and antimicrobials by a factor of about 10. Li et al. developed gold-based immunosensors with a bilayer lipid screen that was hostile to penicillin G to detect trace amounts penicillin G at the value specified by the European Association (4 μg/L) [183]. The intended sensor might also be used as a fast penicillin G screening detection tool. This sensor proved to be more effective and beneficial than standard HPLC.

4.3.2. Tetracycline

Antibiotic medicines (TET) have numerous applications in targeting Gram-positive and Gram-negative bacteria and pathogens. They are also often used as food additives in farming areas. Tang et al. designed a sensor to detect TET. When used as a cover for a GCE and AuNPs, MoS₂ and TiO₂ provided a large surface area due to their circular design [188]. A roundabout electrochemical identification approach for TET was used to complete the suggested sensor. In a different investigation, CV and EIS were used to investigate the ability of stepwise-produced Fe₃O₄/AuNPs with chitosan to detect TET. This platform was used to test food, and the results revealed a 95.9% recovery rate with a 1.86% standard deviation. Using impedance antimicrobials, the particularity and security of the sensors were investigated [189]. An MIP was also used to create a TET sensor using MWCNTs and AuNPs. As a result, the cathode was projected to have the most detection locations and a higher electron transport rate. The cathode’s improved electrocatalytic performance with AuNPs led to a low LOD of 90 nM for TET when using CV. When the sensor’s selectivity was tested under prevalent disruptions (such as those caused by oxytetracycline, chloramphenicol, and nafcillin), it was discovered that oxytetracycline had a more significant impact than the other two compounds [190].

4.3.3. Kanamycin

As substrates for biosensing, Qin et al. improved a progressive thionine-functionalized graphene and nanoporous (HNP) Pt-Cu composite (GR-TH). When using an HNP-PtCu/GR-TH/GCE, the aptamer designated for kanamycin was arranged using strong interactions among the aptamer and the PtNPs’ amine groups. For kanamycin, the sensor generated a lower LOD of 0.86 pM and a total direct response within the range of 0.001 to 100 nM [191,192]. The sensor also demonstrated good sensitivity for kanamycin in the presence of other competing species, proving its potential for analytical techniques. In addition, the sensor exhibited great functional use and good solidness in milk tests.

4.3.4. Chloramphenicol

A specialist medication in fighting both Gram-negative and -positive bacterial microorganisms is chloramphenicol (CAP). An electrochemical sensor was developed using rGO and palladium nanoparticles [193] to degrade CAP. It involved a transmission electron magnifying lens in its construction. The electrochemical experiment was achieved by utilizing a sensor that was examined by CV and DPV as an easy-to-understand procedure for the recognition of actual samples, such as honey and tap water. The creators inspected the impacts of different boundaries. They found upgraded dependability, selectivity, and a broad range for the detection of CAP utilizing the electrochemical sensor. CAP’s nitroso subordinates were considered, and the response component was presented as a two-electron and two-proton movement mechanism. Chen et al. used a molybdenum sulfide/polyaniline nanocomposite (MoS2/PANI) to construct an electrochemical sensor that demonstrated a broad range over three significant degrees and additional notable electrochemical benefits. Under a neutral pH, its actual capability for CAP detection was confirmed [194]. Recently, the electrocatalyst europium oxide (Eu₂O₃) has come into focus as a possible CAP detection catalyst. The Eu₂O₃/rGO nanocomposite showed increased repeatability and awareness for the detection of CAP in honey and milk and had excellent electric conductivity, dependability, and adaptability and a large, electrochemically accessible surface area [195].

4.4. Antifungal Drugs

The progress in creating drugs to combat fungal infections has not kept pace with the advancements in the development of drugs to fight bacterial infections. This is not surprising given the cellular characteristics of the species involved in such interactions. Bacteria, being prokaryotic organisms, present various structural and metabolic aspects that are different from those found in the human host. In contrast, because fungi are eukaryotes, most poisonous substances harm the organisms that they infect. Additionally, the measurement of fungi is more complex than that of bacteria due to their frequent adoption of multicellular forms and slow growth rates. This problem complicates the process of conducting trials to evaluate the potential antifungal properties of a substance, whether in the laboratory or in living organisms. Despite these drawbacks, there have been significant advancements in the discovery of novel antifungal drugs and our knowledge of those already in use.

Parasitic medications (antimycotics) are utilized to combat infectious diseases by destroying or preventing the spread of low-risk growths within an organism. The activity of such drugs can occur in the interior or exterior, where their performance depends on their communication with the host’s immune system. For instance, organisms that affect the feet exhibit strong odors but are not unsafe; meanwhile, contagious diseases of the blood and tissue can be deadly. This section explains how fungicides like polyenes, azoles, and allylamine may be used in various electrochemical biosensing and detection applications.

4.4.1. Natamycin

Natamycin is the sole approved polyene-type drug for the treatment of infectious keratitis. One group studied the electrochemical properties of natamycin by employing a carbon paste electrode (CPE) and conducting differential pulse voltammetry (DPV) within feasible packaging conditions [196]. SWCNTs were immobilized on the poly(L-serine)/GCE surface, leading to another approach to identifying natamycin. The current was significantly increased and made as low as feasible by altering the open circuit potential [197]. A robust, high-strength, and high-selectivity integrated graphene oxide/MWCNT sensor was developed for the detection of natamycin [198]. Authors have also explored the electrochemical detection of natamycin by modifying an SPCE using nanocomposites of MWCNTs with platinum-doped cadmium sulfide [199]. A homogenized yogurt beverage spiked with a known type of natamycin was used to evaluate the suggested Pt-compact disc/MWCNT/SPCE sensor, proving the practicality of this method for the specific determination of natamycin in the food industry.

4.4.2. Fluconazole

The fluorine-joined bis-triazole called fluconazole (influenza) is an anti-contagious drug for the treatment of vaginitis caused by vaginal yeast and recurrent Candida infections. Additionally, it serves as a preventative and healing medication for people who have undergone bone marrow transplants. The electrochemical analysis of this drug at the surface of a Pt electrode and GCE exhibited a pH-dependent oxidation mechanism that enhanced the current at pH 8, and it revealed anodic potential of ~0.85 V. This process involved passing a triazolic ring electron, producing an extreme charge, and then performing additional dimerization steps to create a bis-compound object. Utilizing an electrochemical approach, the ability of the drug to securely adsorb to the cathode surface was examined, raising questions regarding its scientific limitations, including its awareness, linearity, and reproducibility. An innovative Fe₃O₄@PA-Ni@Pd/chitosan nanocomposite-modified carbon ionic fluid terminal, as shown in Figure 7, was prepared for the sensitive detection of influenza to solve this problem [200]. Several relapse examinations were used to optimize the trial conditions. This figure illustrates how the collection duration and nanoparticle fixation affect the 3D response surface of the electrochemical current. The CV responses of the developed sensor to influenza were recorded at various output rates ranging between 10 and 500 mV/s. The proposed sensor was approved by quantifying influenza in plasma and urine samples, demonstrating excellent selectivity. With an LOD of 3.5 nM, it also displayed a broad detection range of 0.01 to 400 μM [200].

Nagatani et al. described a semi-real-time electrochemical monitoring approach for influenza virus RNA based on reverse transcription loop-mediated isothermal amplification (RT-LAMP) in [201]. The peak height of the current was determined by the amount of input RNA and the degree of DNA amplification used.

4.4.3. Ketoconazole

This drug is utilized as an oral medication because of its low toxicity and flexible application throughout the circulation system, urine, saliva, and other liquids. Peng and associates used CV and a GCE to investigate ketoconazole’s electrochemical and adsorptive characteristics. On the other hand, DPV demonstrated good awareness and selectivity when used for electrochemical identification in the presence of potential contaminant particles. In another study, ciclopirox olamine, a pyridine antagonist to certain compounds used in beauty products, was identified using a BDDE and the electrochemical analysis of ketoconazole. Ketoconazole and ciclopirox olamine’s optimum electrochemical oxidation were examined using SWV, and the results showed that ketoconazole had a dependence ratio of 0.29 to 3.13 μM. In comparison, that of ciclopirox olamine ranged from 25.3 to 419 μM. The qualitative and quantitative electrochemical tests using ketoconazole succeeded with a straightforward setup. For the evaluation of ciclopirox olamine, however, a neutral pH seemed preferable [202].

4.4.4. Tolnaftate

An antifungal medication called tolnaftate (TNF) has been used for a long time to target various microbes and other types of microspores, which can cause several infectious disorders. For the electroanalysis of TNF, disposable SPEs were used, providing a sensitive and repeatable electrochemical platform for the differentiation of TNF and its dynamic hydrolysis products. When the pH ranged from 2 to 10, reasonable irreversible oxidation was seen at 1.20 V with a direct range of 0.24 to 3.76 μM. It was shown that the electrooxidation was a dispersion-controlled process that involved a single electron moving in response to the entrance of a water particle [203].

4.4.5. Clioquinol

A skin medication called clioquinol (CQL) is used to treat subacute myeloid-optic neuropathies and gastrointestinal infections. Tin molybdate (SnMoO4)2 nanoplates demonstrated improved responsiveness, remarkable stability, and good selectivity when used for the electrochemical detection of CQL. With only a few common metal particles in its field of view, this sensor displayed an LOD of 14 nM. Three-layered blossom-like cerium vanadate (CeVO₄) was used to continuously examine CQL in organic samples. CV and DPV evaluated the CeVO₄-modified SPCE’s electrocatalytic performance for the electrochemical detection of CQL [204]. The developed platform’s progressive application to the examination of the spiking of CQL (a known focus) in human urine tests yielded a recovery range of 97.5 to 105% for various durations, illuminating the potential uses of the developed sensor in various electrochemical detection applications [205].

4.5. Antiviral Medicines

The antiviral medications currently available consist of over 40 substances that have been officially certified for clinical consumption. At least half of the licensed drugs are used to treat human immunodeficiency virus (HIV) infections, most of which are recent discoveries from the past five years. The other antivirals currently on the market are mainly used to treat infections caused by the virus. Antiviral medications include a number of compounds used to treat various common illnesses, from seasonal infections to human immunodeficiency virus. Most popular drugs are controlled intravenously as opposed to orally. The excessive consumption of antiviral medicines can render the body incapable of fighting other viral diseases; hence, quantitative and subjective investigation is essential.

4.5.1. Acyclovir

Acyclovir (ACV) is an oral and intravenous drug that is used to treat viral illnesses such as varicella zoster, hepatitis B, and herpes simplex. The improved direct electrochemical identification of ACV in a broad range was made possible by the collective energy between MWCNTs and dihexadecyl hydrogen phosphate (DHP). Due to its highly electrochemically dynamic surface region, the empty nanostructured film anode improved the electrochemical identification of ACV. The suggested detection platform was used to study an economically viable ACV pill, demonstrating potential and practical use. Wang et al. modified a CPE using polyvinylpyrrolidone (PVP) and a macromolecule surfactant [206]. The PVP-modified CPE terminal significantly boosted the oxidation signal with an LOD of 2.5 nM, with two-electron and two-proton oxidation components involved in the electrochemical oxidation. For the electrochemical identification of ACV, a few parameters, including the pH, collection time, collection potential, and PVP focus, were enhanced. The method used for the electrochemical investigation was compared to HPLC, demonstrating excellent results and validating its accuracy. Radical hydroxy-guanine and oxo-guanine were produced because the ACV was electrochemically oxidized on the PGE, which was found to be an extensive and irreversible oxidation process [207].

There has been much interest in manufacturing chemically synthesized electrodes for sensor applications. For the minute detection of compounds, CPEs coated with one or more nanoparticles have provided impressive results in the search for novel materials. In the work of Shetti et al. [208], γ-Fe₂O₃ nanoparticles and bentonite clay particles were used as modifiers in a CPE to measure the antiviral drug ACV. The outcomes also demonstrated the sensor’s sensitive pharmacokinetic performance.

4.5.2. Ganciclovir (GCV)

For the treatment of Epstein–Barr virus, herpes, and cytomegalovirus, GCV has received clinical approval. It has been confirmed that electrochemical oxidation in a GCE is a simple, quick, and delicate approach for the identification of GCV in serum and drug testing [209]. The crucial process that caused the current to increase was the oxidation of the guanine component using electrochemistry. However, regarding the degree of GCV oxidation, the analyte particles were not oxidized concurrently. A boron-doped nanocrystal jewel (BDND) cathode performed well in a different investigation when used with GCV at pH 2.5; when employing DPV, the peak current at 1.2 V rose directly with the increase in focus. The BDND sensor also showed significantly better security than a GCE, thanks to the decreased oxygen groups created following electrooxidation, which reduced the extent of the infection [210]. The CV of 100 μM GCV with different electrodes revealed that the electrochemical oxidation of GCV was more active with AuNPs/MIP/MWCNTs/GCE [211].

4.5.3. Zanamivir (ZAV)

ZAV is another medication utilized against influenza A H5N1 and H1N1 infections. Although ZAV is a fascinating compound, its electrochemical examination has yet to be considered because it is not among the most popular medications. Skrzypek used square wave adsorptive stripping voltammetry on a mercury-doped cathode to investigate the electrochemical oxidation of ZAV. They discovered that the solution’s pH had no significant effect on the process, with the greatest current obtained at pH 2.2 [212]. Focusing on the electrochemical oxidation of ZAV, an Au-based sensor was proposed by Wahyuni et al. to identify the exosialidase protein neuraminidase (NA), which is involved in several diseases. This is because, although NA is not directly electrochemically oxidized, its connection to ZAV shifts the maximum potential for ZAV decomposition while considering the unique position of NA [213].

4.5.4. Valacyclovir (VCV) and Acetaminophen

The use of numerous medications is a standard clinical procedure to treat infections and their side effects. Antiviral and antipyretic drugs can offer resources in the fight against many diseases. However, the observation of these groups of medications is required in this context. In this way, the synchronous detection of VCV and acetaminophen was proposed using rGO. The CV of acetaminophen and VCV obtained using a GCE and rGO/GCE demonstrated the potential for simultaneous acetaminophen and VCV detection utilizing rGO/GCEs [214]. To create 8-oxovalacyclovir, two electrons and two protons are used in an electrooxidation interaction. They are not entirely predetermined to be diffusion-controlled and irreversible.

4.6. Anticancer Medication

In the context of disease, drugs show usefulness in eliminating malignant cells, combating cancer, preventing the disease from metastasizing and spreading, and alleviating different side effects. These medications’ creation and standard clinical utilization require ready-to-use, subjective, and quantitative examination tools. This section features a few recent improvements in the electrochemical detection of anticancer drugs.

4.6.1. Taxol

Taxol is obtained from a standard mixture of the Pacific yew tree’s stem bark. It is a powerful medication to target cancerous growth in the breast, ovarian cancer, and non-small-cell lung cancer. An insightful technique was created to detect Taxol by utilizing cathodic stripping SWV. Taxol was discovered under a soluble base using a mercury drop electrode with an interfacial contact area of 0.0278 cm² [215]. The primary basis of efforts to produce and develop Taxol detectors has been DPV using PGEs, which is hindered by its interaction with twofold abandoned DNA (ds-DNA). In a study, this interaction lowered the strength of the guanine and adenine oxidation signals in the predicted range of 0.5 to 1.3 V, allowing the electroanalysis of Taxol to be completed with a detection range of 0.2 to 10.0 µM [216]. The favorable electron motion characteristics and the highly dynamic regions increased the voltammetric oxidation of Taxol. The designed nanocomposite electrode offers a sensitive, robust, and specific detection platform [217].

4.6.2. Doxorubicin

Doxorubicin, an anthracycline drug produced by the bacterium Streptomyces peucetius var. caesius, is applied to treat many leukemias and lung and breast cancers. Using a working electrode composed of carbon, doxorubicin was swiftly and thoroughly examined. The pseudo-reversible reaction involved an acetic acid derivative, which was suggested as the driving force behind the electrochemical catalysis. This was supported by a unique change that occurred when the pH value was increased, potentially leading to undesirable results [218]. The final uses for these sensors lie in medicine and the environment. Nicole and colleagues developed a drug discovery technique using single nucleic acids that could attach to target particles (aptasensor). The experiment continued with an extensive detection range of 4 to 1000 nM, with the immersion of the aptamer–gold cathode occurring at 125 nM [219]. In contrast, distinguishing between two drugs increases a particular detection platform’s cost, viability, and effectiveness. It could be possible to devise an approach to identify doxorubicin and another anti-disease agent (methotrexate) for the evaluation of pharmaceutical, healthcare, and natural products. An integrated cyclodextrin–graphene nanocomposite on a GCE (Cd GN/GCE) was used to distribute doxorubicin and methotrexate concurrently. Doxorubicin and methotrexate’s peak flows on the disc, compared to the data displayed on an exposed GCE, rose by 26.5 and 23.7 times, respectively [220]. Another oligonucleotide metal (DNA/silver)-dependent detector for the identification of doxorubicin was designed using steady-state voltammetry. The TEM images of the silver nanoparticles following synthesis with the introduction of doxorubicin confirmed that the Ag nanoparticles were successful. When doxorubicin stacking with AgNPs amounting to ∼17 (red line) and ∼1 (dark line) was used in the proposed system, the correlation of the voltammetric data calculated using 0.3 M of KCl showed that the responsiveness dropped as the level of doxorubicin stacking increased because of the drug’s complex binding.

4.6.3. Imatinib and Flutamide

Malignant growth inhibitors for gastrointestinal and stromal tumors and leukemia, such as imatinib (IMA), are effective in the treatment of these diseases (essences). This type of medicine should be monitored in bodily fluids such as plasma, urine, cerebral fluid, and blood. A dendrimer-layered empty fiber graphene oxide sensor was developed to micro-extract and electrochemically identify biochemical samples, including IMA [221]. Three cancer-preventative drugs with excellent selectivity for IMA and an identity threshold of 7.39 nM were used in obstruction research. SPCEs were used to disseminate sensor information, enabling inexpensive, quick-acting, and simple sensors to quantitatively identify numerous drugs [222]. For instance, the voltammetric detection of IMA was accomplished utilizing SPCEs (CNT). It exhibited the piperazine ring oxidative conductivity of IMA at a peak potential of 0.75 V. Despite any additional decrease due to the massive increase in current from 0.71 V, this electrode showed outstanding results under a synergistic and irreversible cycle and it was found to be an adsorption-controlled process.

Additionally, the suitability of the SPCEs for the projected area was compared with that of platinum- and gold-functionalized electrocatalysts, where the two anodes were successful. Several drugs are given to immunocompromised individuals directly, orally, forcibly, or chronically. In this case, one medication may restrict the activity of another, which could bring about serious side effects, or changes to their doses might be required. To avoid these problems, synchronous medication detection is attractive. With the aid of a metal oxide/carbon-based electrode (NiO-ZnO/MWCNT-COOH/GCE), the simultaneous recognition of a drug (IMA) and an antifungal (Itraconazole) was investigated. Itraconazole’s maximum oxidation current increased in DPV with an LOD of 4.1 nM and 2.64 μA/µM/cm², indicating excellent responsiveness. IMA had responsiveness of 9.64 μA/µM/cm², an LOD of 2.4 nM, and a linear range of 0.015 to 2.0 µM [223]. Moreover, Tseng et al. described a nanocatalyst for the electrochemical detection of flutamide, a non-steroidal antiandrogen used in the medical field to treat leukemia and prostate conditions, consisting of graphene oxide sheets and calcium titanium oxide (GOS/CaTiO₃). Based on the XRD, TEM, and EDX results, Figure 8 shows the proposed nanocatalyst’s shape, design, and structure. This figure demonstrates a broad range (0.015 to 1184 μM), a low LOD (5.7 nM), and high responsiveness (1.073 μA/µM/cm²). Human blood and urine tests were used to evaluate the sensor, demonstrating its potential for use in malignant growth and drug localization [224].

Table 1. Various electrochemical sensors for the detection of pharmaceutical drugs. Reproduced with permission from [42].

Electrode	Analyte	LOD (μmol/L)	Linear Range (μmol/L)	Ref.
SPCE/(CSþAuNPs)	Aspirin	0.03 pg/mL	1 pg/mL–1 μg/mL	[225]
CuNCs/CuE	Mefenamic acid	1 nM	4 nM–10 mM	[226]
CS-CuNCs/CuE	Indomethacin	1 nM	1 nM–10 mM	[226]
AuNPs/MWCNTs/GCE	Diclofenac sodium	0.02 μM	0.03–200 μM	[227]
PtNFs/RGO/SPE	Diclofenac	40 nM	0.1–100 μM	[228]
G-DVD/GO/AgNPs@b-CD	Naproxen	0.023 μM	0.4–80 μM	[146]
GO-COOH/GCE	Diclofenac	0.09 μM	1.2–400 μM	[229]
GO/GCE	Naproxen	1.94 μM	10 μM–1 μM	[230]
GO/CPE	Flufenamic acid	5.0 nM	0.001–0.09 μM	[231]
Graphite rod	Diclofenac	0.76 μM	2.56–9.5 μM	[232]
PDDA-GR/GCE	Diclofenac	0.609 μM	10–100 μM	[233]
Nano-sepiolite/MWCNTs/PGE	Paracetamol	0.018 μM	0.059–60 μM	[234]
SD-MWCNTs/GCE	Ibuprofen	1.9 μM	10–1000 μM	[235]
FMWCNTs/b-CD/CPE	Piroxicam	0.7 μM	10−6–10−2 M	[236]
Pt-N-RGO-SWCNTs/GCE	Piroxicam	5.0 ng/mL	0.02–20 μg/mL	[237]
GNP-CNF/GCE	Nepafenac	63 nM	4.0–15 μM	[238]
NDCNDs/CoTAPhPcNPs/GCE	Aspirin	9.66 nM	-	[239]
CuO/GCE	ASA	0.037 μM	0.1–714 μM	[240]
TiO2 NPs/GCE	Nimesulide	3.37 nM	0.1–40 μM	[241]
N-CQD/Cu2O/GCE	Aspirin	0.002 μM	1–907 μM	[242]
GNS/PANI/Bi2O3/GCE	Etodolac	10.03 ngmL−1	20–100 ngmL−1	[243]
f-CNF/LaCoO3/GCE	4-AAP	1.0 nM	0.001–1374 μM	[244]
Iron oxide NPs/CPE	Diclofenac	2.45 nM	0.01–100 μM	[245]
Pt-NiO/MWCNTs/GCE	Piroxicam, Amlodipine	0.061 μM	0.6–320.0 mM	[246]
XAD/CPE	Flufenamic acid	3.6 nM	0.05–8.0 μM	[247]
Ag-TiO2/XAD/CPE	Flufenamic acid	1.2 nM	0.05–8.0 μM	[247]
Ru-TiO2/MWCNTs/CPE	Flufenamic acid	0.68 nM	0.01–0.9 μM	[248]
Ru-TiO2/MWCNTs/CPE	Mefenamic acid	0.45 nM	0.01–0.9 μM	[248]
Oxygen plasma-treated ZnO/SPE	Dopamine, Diclofenac	0.28 μM	0.1–300 μM	[249]
Cu5V2O10/CPE	Mefenamic acid	2.34 nM	0.01–470 μM	[250]
AgNPs-ChCl-GO/CPE	Celecoxib	2.51 nM	9.6 nM–0.74 μM	[251]
AuNPs-ChCl-GO/CPE	Meloxicam	1.008 nM	9.0 nM–0.85 μM	[252]
ER-GONRs/SPCE	Nimesulide	3.50 nM	0.01 μM–1.50 mM	[253]
NiNPs/ERGO/GCE	Diclofenac	0.09 μM	0.25–125.00 μM	[254]
f-MWCNTs/NC/GCE	Diclofenac	0.012 μM	0.05–250.0 μM	[255]
BaNb2O6NFs/CPE	Lornoxicam	0.639 nM	4.0 nM–0.25 mM	[256]
SWCNTs/GCE	Mefenamic acid	13.4 nM	0.1–35 μM	[257]
CP-BDDE	Pravastatin	0.204 μM	1.08–16.4 μM	[258]
MWCNTs/CPE	Diclofenac	0.74 μM	2.49–10 μM	[259]
Nano-smectite/MWCNTs/PGE	AA	0.096 μM	0.319–60.0 μM	[260]
Fe3O4/Gluta/MWCNTs/CPE	Aspirin	11.8 nM	20–170 μM	[261]
AuNPs/Graphene/CILE	Celecoxib	0.2 μM	0.5–15 μM	[163]
AgNPs/SWCNTs/rGO/GCE	Piroxicam	0.5 μM	1.5–400 μM	[262]
Al2O3 microparticles/GCE	Naproxen	12 nM	50–500 nM	[263]
FTO/BiVO4/CuO	Naproxen	5 nM	5–480 nM	[264]
MWCNTs-IL/CCE	Indomethacin	260 nM	1–50 μM	[265]
Polychitosan-CuNPs/CuE	Mefenamic acid	0.004 μM	0.004–10,000 μM	[266]
Carbon paper-based sensor	Ketoprofen	0.11 μM	0.088–1.96 μM	[267]
PANI-rGO-MIP/CPE	Diclofenac	1.1 mgL−1	5–80 mgL−1	[268]
PANI/MnO2-Sb2O3/FTO	ASA	0.20 nM	1.2–228.68 nM	[269]
PEDOT/GCE	Diclofenac	9.06 nM	50.0–250 nM	[270]
RGO-PEDOT-PSS/GCE	Piroxicam, Nimesulide	0.1 μM	0.87–26 μM	[271]
TiO2-PEDOT/GCE	AA	0.02 μM	6–46 μM	[272]
PEDOT/TiO2/[BMIM]Cl/CPE	Diclofenac	11.7 nM	50–100 μM	[273]
Glucose/CPE	Mefenamic acid	1.01 nM	25 nM–500 μM	[274]
Nano-silica/CPE	Mefenamic acid	1.0 nM	0.2–5 μM	[275]
Fe(III)-SBMCP/CPE	Mefenamic acid	0.02 μM	0.05–150 μM	[276]
Carbon ionic liquid electrode	Piroxicam	40 μM	0.2–60 μM	[277]
Nanoclay/CPE	Nimesulide	1.01 nM	0.01–0.35 μM	[278]
HMDE	Tetrazine	27.8 nM	0.02–15.2 μM	[279]
MB/Cu/Ti3C2Tx/GCE	Piroxicam	0.05 μM	0.1–80 μM	[280]
MB/Apt/MWCNTs/IL/Chitosan/GCE	Ibuprofen	20 pM	70 pM–6 μM	[281]
Apt-Den-QDs/GCE	Ibuprofen	333 fM	0.001–12 nM	[282]
MWCNTs/msCYP1A2-SPE	Naproxen	16 μM	9–300 μM	[147]
Apt/MWCNTs/GO/Fe3O4/GCE	Diclofenac	33 pM	100–1300 pM	[283]
DCF-Probe/E-Probe/GCE	Diclofenac	0.1 pM	10−14 M–10−10 M	[284]
Apt/NiHCF/PtNPs/PEI/MWCNTs/Au	Diclofenac	2.7 nM	10–200 nM	[285]
GCE/AHA/DBA	Diclofenac	0.27 μM	0–5 μM	[286]
Apt/CdTeQD/GCE	Ibuprofen	16 pM	0.05–20,000 nM	[287]
Au/SAM/Hydrogel/Apt	Diclofenac	0.02 nM	30 pM−1 μM	[288]
Apt/AuNPs/GCE	Ibuprofen	0.5 pM	0.05–7 nM	[153]
Apt/AuNPs@N-GQDs/GCE	Ibuprofen	33.33 aM	10−7–200 nM	[289]

shows various electrochemical sensors for the detection of pharmaceutical drugs.

5. Limitations

Nanomaterial-based electrochemical sensors hold great promise for drug detection and monitoring applications but face several potential drawbacks. Challenges include signal interference, durability under clinical conditions, and the scaling of these technologies for widespread use.

5.1. Signal Interference

Electrochemical sensors are commonly used in complex biological fluids like blood, serum, and urine but face performance challenges. A significant issue is fouling, where proteins and biomolecules adsorb onto the sensor surface, obstructing access to active sites and reducing the sensitivity. For example, substances like albumin can hinder the accurate detection of target analytes. Redox interference is another challenge, as biological samples often contain endogenous redox-active species that can mimic the target analyte, leading to false positives. Compounds like ascorbic acid may interfere with medications like ibuprofen. Additionally, matrix effects from variations in the biological fluid’s composition—such as the pH, ionic strength, and temperature—can complicate signal interpretation, resulting in inconsistent readings.

• Interference from complex biological fluids

Biological fluids, like blood and serum, present challenges for electrochemical sensors due to their complex composition. Fouling is vital, where proteins and biomolecules coat the sensor’s surface, obstructing the interaction with target analytes such as ibuprofen, thereby reducing the sensitivity and specificity. Additionally, redox interference complicates detection, as endogenous redox-active species like ascorbic acid can produce overlapping signals with the analyte, resulting in false positives or negatives. Variability in the pH and ionic strength further affect sensors’ performance. Fluctuations in these parameters can alter the charge and solubility of the target analyte, leading to inconsistent results and decreased reliability.

ii.

Nanomaterial instability

Nanomaterials enhance sensors’ sensitivity but face stability issues that affect their performance. A significant concern is oxidation, especially in carbon-based materials, which can result in decreased conductivity and reduced active surface areas, lowering the responsiveness. Agglomeration also poses a problem, as nanoparticles clump together, diminishing the surface area for essential electrochemical reactions and impacting the sensitivity. Additionally, the leaching of components, such as polymers or ions from gold nanoparticles, may alter the sensor characteristics and lead to inconsistent readings.

iii.

Mitigation strategies

Researchers are tackling the challenges of developing electrochemical sensors through innovative strategies. One key approach is surface modification with biocompatible coatings, which reduce fouling and enhance the stability by minimizing nonspecific adsorption and protecting nanomaterials. Additionally, the combination of various nanomaterials, like carbon nanotubes with metal nanoparticles, creates effective nanocomposites that boost sensors’ performance. Advanced signal processing algorithms and machine learning techniques also improve the accuracy by differentiating target signals from interferences in complex biological samples.

5.2. Durability Under Clinical Conditions

Nanomaterials often face stability challenges that affect the long-term performance of electrochemical sensors, particularly in clinical settings, where the conditions can vary. They are sensitive to the temperature, humidity, and reactive species, leading to issues like the oxidation or clumping of metal nanoparticles, which reduces their effectiveness. Mechanical durability is critical; sensors must withstand temperature shifts and physical stress. Fragile nanostructures may deteriorate over time, resulting in decreased performance or failure. Additionally, prolonged use can cause chemical degradation, leading to the loss of active sites that reduces the sensitivity and alters the selectivity—critical factors for reliable clinical performance.

5.3. Challenges in Scaling for Widespread Use

Transitioning from laboratory-scale development to the large-scale production of nanomaterial-based sensors presents significant challenges. Key hurdles include the complexity and cost of manufacturing high-quality nanomaterial coatings and the difficulty of standardizing the processes for mass production while maintaining performance. Quality control is also crucial, as uniformity in the properties of nanomaterials across production batches is essential. Even minor variations can lead to significant differences in sensor behavior, making quality assurance complex. Additionally, the navigation of regulatory challenges is necessary before electrochemical sensors can be approved for clinical use. The lengthy process of demonstrating safety and efficacy can delay the adoption of these technologies in healthcare.

6. Conclusions and Outlook

Advanced electrochemical sensors offer great potential for the detection of drug intensities, but it is crucial to understand the physical, chemical, and electrical interactions between the nanomaterials and target analytes. Investigating the subatomic structures of various pharmacological compounds and nanomaterials, as well as the electrochemical techniques and associated factors, would contribute to the current detector and biomarker research, particularly regarding their sensitivities and LODs. Combining metal nanoparticles, quantum dots, scalable organic groups, and nanocomposites in carbon-based nanostructures produces a synergistic effect to react with the analyte. Nanoparticle- or natural particle-functionalized cathodes have shown a low LOD and superior performance for small subatomic medicines such as headache medications, ibuprofen, and sertraline.

Electrochemical technology has advanced biomedical applications in disease prediction, real-time monitoring, and drug screening. However, there are still significant difficulties in acquiring target signals due to the method’s dependency on wires, slow response times, and difficulties in verification. New technologies such as Bluetooth, wireless power transfer (WPT), and near-field communication (NFC) could make electrochemical data transmission quicker and better.

It is crucial to consider wireless platforms and the desired usability to adopt electrochemical biosensors, while the miniaturization of electrochemical instruments and advancements in the assembly of biosensors are expected. Electrochemical sensors and biosensors should have their costs and reliability carefully evaluated, along with their responsiveness and selectivity.

One of the emerging trends is the combination of mass spectrometry or fluid chromatography with electrochemical detection to identify therapeutic molecules effectively. In summary, developing advanced electrochemical sensors and biosensors to detect drug intensities requires a comprehensive understanding of nanomaterials and their interactions with target analytes.

The integration of quantum computing and AI with emerging technologies is poised to significantly enhance the capabilities in various fields, particularly electrochemical sensing and materials science. As quantum computing evolves, it could facilitate the development of advanced algorithms that optimize the electrospinning process for nanofiber production. This optimization could lead to nanofibers with tailored properties for specific applications, such as drug delivery and tissue engineering. Moreover, using AI with electrochemical sensors could improve real-time data processing and analysis, enabling the faster and more accurate detection of chemical compounds. This synergy could revolutionize personalized medicine by allowing for the rapid assessment of drug efficacy and patient-specific responses, thus paving the way for more effective treatment plans. In the context of materials science, combining quantum computing with hybrid chip technologies could enhance electronic systems’ performance, addressing energy consumption and sustainability challenges. By leveraging the unique properties of 2D materials and their integration into IoT applications, researchers can develop more efficient sensors and communication systems, which are essential for the future of connected devices. The intersection of quantum computing, AI, and advanced materials technologies is promising to drive innovation in drug detection, personalized medicine, and sustainable electronic systems.