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Review

Electroanalysis Advances in Pharmaceutical Sciences: Applications and Challenges Ahead

1
Chitkara College of Pharmacy, Chitkara University, Rajpura 140401, Punjab, India
2
Department of Pharmaceutical Sciences and Technology, Maharaja Ranjit Singh Punjab Technical University, Bathinda 151001, Punjab, India
3
Faculty of Pharmaceutical Sciences, The ICFAI University, Baddi 174103, Himachal Pradesh, India
4
Gramothan Vidyapeeth Home Science Girls PG College, Sangaria 335063, Rajasthan, India
5
Department of Biotechnology, Graphic Era Deemed to be University, Dehradun 248002, Uttarakhand, India
6
Department of Pharmaceutical Sciences, HNB Garhwal University, Chauras Campus, Srinagar 246174, Uttarakhand, India
*
Authors to whom correspondence should be addressed.
Analytica 2025, 6(2), 12; https://doi.org/10.3390/analytica6020012
Submission received: 2 February 2025 / Revised: 24 March 2025 / Accepted: 27 March 2025 / Published: 30 March 2025
(This article belongs to the Section Electroanalysis)

Abstract

:
Electroanalysis has emerged as a critical tool in the pharmaceutical industry, offering versatile and sensitive methods for drug analysis. This review explores the principles, techniques, and applications of electroanalysis in pharmaceuticals, emphasizing its role in drug development, quality assurance, pharmacokinetics, and environmental monitoring. Key electroanalytical methods, including voltammetry, potentiometry, and amperometry, are detailed along with their practical applications, such as detecting active pharmaceutical ingredients, monitoring drug metabolites, and ensuring product stability. Innovations in electrode materials and biosensors have enhanced their sensitivity and specificity, paving the way for advanced drug screening and therapeutic monitoring. Challenges like electrode fouling, selectivity issues, and regulatory constraints are discussed, along with strategies to overcome them. Future trends highlight the integration of nanotechnology, AI, and portable sensors to facilitate real-time analysis and personalized medicine. These advancements position electroanalysis as an indispensable component of modern pharmaceutical research and healthcare. Future perspectives emphasize the integration of nanotechnology and artificial intelligence (AI) to optimize experimental processes and data interpretation. This study also predicts the increased adoption of lab-on-a-chip systems and bioelectrochemical sensors to meet the growing demand for precision medicine and sustainable pharmaceutical practices. These advancements position electroanalysis as a cornerstone of pharmaceutical research, paving the way for more efficient drug development, improved patient outcomes and better environmental management. This comprehensive review underscores the transformative potential of electroanalysis in addressing the evolving challenges of the pharmaceutical industry and provides a foundation for future innovations. This review does not explicitly define the timeframe for the considered advancements. However, it discusses recent technological developments, including innovations in nanostructured electrodes, microfluidic integration, and AI-driven data analysis, indicating a focus on advancements primarily from the last few years, i.e., from 2020 to 2025.

1. Introduction

Electroanalysis encompasses a broad range of analytical techniques that rely on the measurement of electrical properties, such as current, voltage, and charge, to detect and quantify chemical species. These techniques are essential tools in analytical chemistry, offering high sensitivity and selectivity, as well as the ability to analyze complex matrices. Analytical techniques that utilize electrical properties to detect and measure chemical compounds. These approaches are vital in several scientific disciplines, particularly in the pharmaceutical business, where precision and accuracy in measuring chemical components are critical [1]. Drug and metabolite detection in biological fluids is crucial for pharmaceutical and biomedical research. Recent advancements in electrochemical instruments have made electroanalytical approaches a viable option for pharmaceutical analysis. Modern electrochemical techniques offer high detection limits and a broad dynamic range [2].
Electroanalytical techniques require small sample quantities, frequently in the microliter range, and have low detection limits, enabling the investigation of subpicogram levels of drug compounds and metabolites [3]. Electrochemical techniques are used in electroanalytical chemistry to analyze chemical species, emphasizing the chemical reaction of electrical stimulation. Four essential factors are measured in electrochemical experiments: potential, current, charge, and time [4]. The specific parameter applied as the excitation signal influences the system response. A variety of techniques, including voltammetry, polarography (direct current, fast-scan, and differential pulse), linear sweep voltammetry, cyclic voltammetry, hydrodynamic voltammetry, differential pulse voltammetry, square wave voltammetry, and stripping voltammetry, can be employed depending on the chosen parameters and type of electrode used. Electroanalysis has emerged as a powerful analytical tool in pharmaceutical sciences, offering several advantages over traditional techniques like spectrophotometry and chromatography. One of its key benefits is its high sensitivity and selectivity, which enable the detection of trace amounts of drugs, metabolites, and impurities. Unlike chromatography, which often requires extensive sample preparation and expensive solvents, electroanalytical methods operate with minimal sample volumes and offer rapid and cost-effective analysis. Additionally, electroanalysis provides real-time monitoring, which is particularly useful for therapeutic drug monitoring and point-of-care diagnostics. Recent advancements have pushed the boundaries of electroanalysis by integrating nanotechnology, artificial intelligence (AI), and miniaturized sensor technology [5]. Nanostructured electrodes and biosensors enhance sensitivity and selectivity, while AI-driven data interpretation streamlines drug screening and quality control. Developing portable and wearable electrochemical sensors opens new possibilities for real-time patient monitoring, enabling personalized medicine and more precise dosing strategies. With growing concerns about environmental pharmaceutical contamination, electroanalysis is vital for detecting drug residues in water and biological samples. Future innovations, such as lab-on-a-chip devices and bioelectrochemical sensors, will further enhance the efficiency of drug development, regulatory compliance, and sustainable pharmaceutical practices. These advancements have solidified electroanalysis as an indispensable tool in modern pharmaceutical research and healthcare [6].
Electroanalysis is a game changer in multiple scientific fields, offering fast, precise, and cost-effective solutions for detecting and analyzing chemical substances. In environmental science, it plays a crucial role in monitoring pollutants like heavy metals, pesticides, and pharmaceutical residues in water and soil, helping to ensure cleaner ecosystems and regulatory compliance [7]. In food safety and agriculture, electrochemical sensors are used to detect harmful contaminants, pesticide residues, and nutrient levels in crops, contributing to safe food production and sustainable farming. Biomedical research has also greatly benefited from electroanalysis, which has enabled real-time health monitoring through biosensors for glucose and cholesterol, and even early disease detection [8]. The field of energy science relies on electrochemical techniques to optimize batteries, fuel cells, and supercapacitors, thereby pushing the boundaries of renewable energy storage and efficiency. In forensics, portable electrochemical sensors allow rapid on-site drug detection, toxicology screening, and explosive identification, aiding law enforcement in crime investigations. Moreover, industrial applications use electroanalysis for corrosion prevention, electroplating, and quality control, ensuring the durability and reliability of materials used in manufacturing. With advancements in nanotechnology, artificial intelligence, and miniaturized sensor technologies, electroanalysis is continuously expanding its reach and making a significant impact across diverse scientific disciplines [9]. A variety of techniques, including voltammetry, polarography (direct current, fast-scan, and differential pulse), linear sweep voltammetry, cyclic voltammetry, hydrodynamic voltammetry, differential pulse voltammetry, square wave voltammetry, and stripping voltammetry, can be employed depending on the chosen parameters and the type of electrode used [10].

Importance of Electroanalysis in the Pharmaceutical Industry

Pharmaceutical and biomedical analysis involves analyzing bulk APIs, intermediate products, formulated products, impurities, products from the degradation of formulations, and biological samples containing drugs and their metabolites. The goal is to obtain data that contribute to the safety, efficacy, and cost-effectiveness of drug therapy. Using quick gradients, samples can be examined individually or as mixtures. It also examines the obstacles and constraints related to these strategies Refs. [5,6]. The healthcare sector relies significantly on electroanalysis for medication research, quality control, and ensuring the safety and efficacy of its products. Electroanalytical techniques offer reliable, sensitive, and cost-effective methods for analyzing complex pharmaceutical compositions [11,12].

2. Fundamentals of Electroanalysis

2.1. Principles of Electrochemical Methods

Electrochemical methods rely on measuring electrical characteristics, including current, voltage, and charge. The analyte and electrode interaction under an applied voltage is the foundation of these approaches, as shown in Figure 1. The redox processes occurring at the electrode surface are critical for the detection and quantification of analytes [13,14].

2.2. Different Electrochemical Techniques

2.2.1. Voltammetry

Voltammetry is a technique for current measurement under an applied voltage. It is well known for its sensitivity and capacity to provide extensive information on the electrochemical behavior of the analytes. This category includes techniques such as differential pulse voltammetry (DPV), cyclic voltammetry (CV), and square wave voltammetry (SWV) [15,16,17].
Voltammetric measurements are straightforward and affordable, allowing rapid data collection. Interpreting quantitative data can be difficult, even for experienced individuals. Pulse approaches have benefited recent voltammetric investigations of electron transfer theories. Furthermore, pulse techniques play a significant role in electroanalysis. Theoretical models can help interpret new stochastic single-molecule and single-nanoparticle approaches, providing insights into the nanoscale mechanisms. The random walk approach is useful for simulating the Brownian movement of nanoparticles and modeling the diffusion of molecules. Random walks are very useful for studying nanoparticle mass transport or electrochemistry, such as nano-impacts, because the concentrations are typically low enough to observe individual nanoparticle reactions. For steady-state voltammetry, a supporting electrolyte to electroactive species ratio of 26 is recommended for full support [18].
Cyclic voltammetry (CV) and pulse voltammetry (PV) are both electroanalytical techniques used to study redox reactions; however, they differ in how they apply voltage and record current responses. Cyclic voltammetry involves sweeping the voltage back and forth across a set range while measuring the resulting current. It provides detailed insights into the electrochemical behavior of compounds, such as their redox potentials and the reaction kinetics. However, CV is more qualitative and is mainly used to study fundamental electrochemical properties rather than for precise quantification [19].
Conversely, pulse voltammetry—which includes techniques like differential pulse voltammetry (DPV) and square wave voltammetry (SWV)—applies a series of voltage pulses instead of a continuous sweep. This pulsed approach significantly reduces the background noise and enhances the sensitivity, making it ideal for detecting trace amounts of substances in complex samples. Pulse voltammetry improves the resolution between closely related electroactive species, allowing better differentiation in mixed samples. Because of its higher sensitivity, lower detection limits, and ability to minimize interference, pulse voltammetry is preferred for real-world sample analysis, especially in pharmaceuticals, environmental monitoring, and biomedical applications, where accurate quantification is essential [20].

2.2.2. Potentiometry

Potentiometry is the measurement of an electrochemical cell’s potential without drawing any current. Ion-selective electrodes (ISEs) are frequently employed in potentiometric assays to estimate the concentration of specific ions, such as pH, which is crucial for pharmaceutical formulations. Polymeric membrane ISEs offer a reliable platform for ion-transfer voltammetry. The applied voltage triggers a redox process at the electrode surface, facilitating ion transfer between the membrane and sample interfaces. The rate of this transfer is quantified as the current [21].
At high concentrations with minimal concentration polarization, the ion-transfer peak position is governed by the logarithm of the analyte ion activity, resembling the potentiometric behavior under zero-current conditions. At low concentrations, where mass transfer is the limiting factor, the peak current exhibits a linear relationship with the analyte concentration, consistent with the observations of other voltammetric methods. Voltammetric ISEs have thinner membranes (less than 1 μm) than potentiometric sensors, overcoming mass transport restrictions [22].
As industries, medicine, and technology advance, ion-selective electrodes (ISEs) are becoming increasingly widely used. To date, numerous improved ion-selective electrodes have been successfully applied to real samples.

2.2.3. Amperometry

Amperometry tracks the current at a fixed potential over time. It is especially effective for detecting electroactive species in a solution. Chronoamperometry and flow injection analysis (FIA) are techniques that increase the speed and efficiency of pharmaceutical examinations. The potential at the ion-selective membrane changes in response to any change in the analyte ion activity, which is balanced by a counterchange in the potential over the capacitive solid-contact material. Integrating the measured current-time transient yields a charge proportional to the logarithmic analyte activity change in the sample [23].
The amperometric approach selectively distinguishes between electroactive species in solution by selecting the appropriate electrode material and applying the appropriate voltage. When a nonspecific potential is applied, the current may include multiple electroactive species. The number of oxidized species increases with positive potential, while the number of reduced species increases with negative potential. Low applied potentials (0.2 V to ±0.2 V) are ideal for detecting analytes without interference [24].

2.3. Electrodes and Sensors Used in Electroanalysis

Electrodes are critical components of electroanalysis. They can be built using a variety of materials, including glassy carbon, platinum, gold, and modified electrodes with specialized sensors for increased selectivity and sensitivity. Advancements in electrode materials, including the incorporation of graphene and carbon nanotubes, have significantly enhanced the performance of electroanalytical methods. Tailoring electrode surfaces with functional layers or micro- and nanostructures has led to the development of new electrochemical devices with diverse applications, particularly in electroanalytical chemistry [25]. X-ray diffraction and diffusion techniques were employed to investigate the structural properties of the ordered electrode surfaces. Two-dimensional small-angle X-ray scattering is more effective than conventional one-dimensional X-ray diffraction in identifying the periodic structural organization of a porous network [26,27].
One of the key advancements in electroanalysis is the modification of electrode surfaces, which enhances the sensitivity, selectivity, and stability of electrochemical measurements. Traditional electrodes, such as glassy carbon, platinum, and gold, can be functionalized with nanomaterials, polymers, or biological molecules to improve their performance. For instance, incorporating graphene, carbon nanotubes, metal nanoparticles, or molecularly imprinted polymers (MIPs) onto the electrode surface increases conductivity, reduces interference, and allows for more precise detection of target analytes. These modifications are particularly beneficial in pharmaceutical analysis, environmental monitoring, and biosensing applications, where detecting trace-level compounds is crucial [28].
A significant innovation in this field is the use of screen-printed electrodes (SPEs), which have revolutionized electroanalysis by making it more accessible, cost-effective, and suitable for real-world applications. SPEs are disposable, portable, and easy to fabricate, allowing for the mass production of customized sensors tailored to specific applications [29]. Unlike traditional electrodes, which require extensive cleaning and maintenance, SPEs offer a convenient and reproducible alternative that is ideal for on-site and point-of-care testing. They have been widely adopted in medical diagnostics (e.g., glucose and biomarker detection), food safety (e.g., pesticide and toxin monitoring), and environmental analysis (e.g., heavy metal detection in water samples). By integrating electrode surface modifications with screen-printing technology, researchers are developing highly sensitive and selective electrochemical sensors that can operate in complex real-world samples with minimal interference. These advancements are pushing electroanalysis beyond traditional laboratory settings, paving the way for rapid, real-time monitoring in healthcare, industry, and environmental science [30].

2.4. Linear Sweep Voltammetry (LSV) and Polarization Methods in Electroanalysis

In electroanalysis, LSV and polarization methods are important techniques that provide key insights into the electrochemical behavior of materials and reactions; however, they are often overlooked in discussions. LSV is a simple electrochemical technique in which the potential of an electrode is gradually increased or decreased in a linear manner while measuring the resulting current. This method helps identify redox potentials, study the reaction kinetics, and characterize the electrode surfaces. LSV is particularly useful for detecting electroactive species in pharmaceutical and environmental samples and is often used in corrosion studies, battery research, and material science to analyze the electrochemical properties of coatings and thin films [31].
Conversely, polarization methods—which include techniques like Tafel analysis, potentiodynamic polarization, and galvanostatic polarization—are essential in corrosion science, fuel cell research, and electrode material characterization. These methods involve applying a controlled potential or current to an electrode and studying its response to assess parameters like corrosion rates, passivation behavior, and reaction mechanisms [32]. Tafel analysis, for example, is widely used to determine the corrosion rate of metals by analyzing their anodic and cathodic polarization curves, while potentiodynamic polarization is useful for evaluating the protective efficiency of coatings and inhibitors [33].
Both LSV and polarization methods are crucial in fields like energy storage, environmental monitoring, and biomedical applications; however, they are often overshadowed by more commonly discussed voltammetric techniques like cyclic voltammetry and pulse voltammetry. Integrating these methods into electroanalytical studies can provide a more comprehensive understanding of electrode behavior, reaction kinetics, and material stability, making them valuable tools for researchers in multiple scientific disciplines [34].

3. Applications of Electroanalysis in Pharmaceutical Industry

3.1. Drug Development and Screening

Electroanalysis provides high sensitivity, selectivity, and cost-effectiveness compared to conventional analytical methods, making it an essential tool for drug development, quality assurance, and regulatory compliance. It highlights four key areas of application: drug development and screening, quality control and assurance, pharmacokinetics and drug metabolism studies, and detection of pharmaceutical residues and contaminants. Electroanalytical techniques are powerful tools for analyzing drug compounds, monitoring their stability, and ensuring product quality. In drug development, these methods aid in screening potential drug candidates by assessing their electrochemical behavior, which is essential for understanding their reactivity and stability. Similarly, in quality control, electroanalysis offers rapid and precise measurements that help maintain the consistency and safety of pharmaceutical products. Furthermore, the study of pharmacokinetics and drug metabolism benefits from electroanalytical methods by simulating biological processes, thus helping predict drug behavior in the human body. Another significant aspect is the detection of pharmaceutical residues and contaminants, where electrochemical sensors and biosensors provide an efficient means of identifying trace amounts of drugs in the environment, ensuring regulatory compliance. Overall, this figure encapsulates the versatility and importance of electroanalysis in pharmaceutical research and industry, offering cost-effective, sensitive, and reliable analytical solutions, as shown in Figure 2. Electroanalysis facilitates the screening of potential drug candidates by providing rapid and reliable measurements of their electrochemical characteristics. This helps identify promising molecules in the early stages of drug development. Cyclic voltammetry techniques can show the redox behavior of drug candidates, which is critical for understanding their pharmacokinetics [35].
The rapid evaluation of electrochemical properties using electroanalysis tools is a vital method in drug discovery because these properties determine the stability, bioavailability, and reactivity of potential drug candidates. Cyclic voltammetry analysis provides essential information about redox reactions to explain electron transfer processes and metabolic pathways, together with biomolecule interactions. This information is essential for optimizing drug design approaches, improving pharmacokinetic properties, and ensuring the safety and effectiveness of newly developed therapeutic agents. Electroanalytical methods enable faster high-throughput screening, which minimizes both the time and expense required for drug development during its initial stages [36,37].

3.2. Quality Control and Assurance

Maintaining the quality and consistency of pharmaceutical products is essential for ensuring their safety and efficacy. Electroanalytical techniques provide precise and reliable methods for quantifying active pharmaceutical ingredients and identifying impurities, thereby ensuring regulatory compliance. Among these techniques, differential pulse voltammetry is particularly effective for detecting trace levels of contaminants in complex formulations, offering high sensitivity and selectivity. Additionally, electroanalytical approaches enable real-time monitoring of drug stability, degradation pathways, and formulation integrity, further enhancing quality control in pharmaceutical manufacturing [38,39,40].

3.3. Pharmacokinetics and Drug Metabolism Studies

Electroanalysis plays a crucial role in investigating drug pharmacokinetics and metabolism by enabling the precise quantification of drug and metabolite concentrations in biological fluids. These data are essential for optimizing dosage regimens and determining the most effective routes of administration. Advanced techniques, such as amperometric biosensors, provide real-time monitoring of drug metabolism, offering continuous and dynamic insights into the absorption, distribution, and elimination processes. Additionally, these electroanalytical methods enhance therapeutic drug monitoring, ensuring personalized treatment strategies while minimizing adverse effects [41,42].

3.4. Detection of Pharmaceutical Residues and Contaminants

Electroanalysis is a valuable tool for detecting pharmaceutical residues and pollutants in various environmental matrices, including water, soil, and biological systems. This capability is crucial for assessing the ecological impact of pharmaceutical compounds and ensuring public health safety. Among electroanalytical techniques, square wave voltammetry is notable for its exceptional sensitivity and selectivity in detecting trace levels of pharmaceuticals in complex environmental samples. By enabling rapid and cost-effective monitoring, these methods contribute to pollution control, wastewater treatment optimization, and regulatory compliance, ultimately aiding in the mitigation of pharmaceutical contaminants in the environment [43,44].

4. Electroanalytical Techniques in Pharmaceutical Analysis

4.1. Voltammetric Methods

4.1.1. Cyclic Voltammetry

Cyclic voltammetry requires the voltage of the working electrode to be swept linearly over time and the resulting current to be measured. This provides useful information regarding the redox behavior of analytes, which is necessary for understanding their chemical characteristics and stability [45,46].

4.1.2. Differential Pulse Voltammetry

Differential pulse voltammetry uses a sequence of potential pulses to detect the current difference before and after each pulse. It improves the sensitivity and resolution of cyclic voltammetry, making it appropriate for detecting low quantities of analytes in complicated pharmaceutical formulations [47,48].

4.1.3. Square Wave Voltammetry

Square wave voltammetry uses a square wave potential superimposed on a staircase potential. It has high sensitivity and is suitable for the trace analysis of medicines. This method is highly effective for identifying impurities and degradation products in pharmaceutical formulations [49,50].

4.2. Potentiometric Methods

4.2.1. Ion-Selective Electrodes

Ion-selective electrodes are used in potentiometry to determine the concentration of specific ions in a solution. They are commonly used in pharmaceutical analysis to determine the amount of ions, such as H+, Na+, and K+, which are crucial for assuring the stability and efficacy of medicinal products [51,52].

4.2.2. pH Measurement

pH measurement is a typical potentiometric method for determining the acidity or alkalinity of medicinal formulations. Accurate pH monitoring is critical for ensuring drug stability, solubility, and bioavailability. Glass electrodes are often used for pH monitoring because of their high sensitivity and dependability [53,54].

4.3. Amperometric Methods

4.3.1. Chronoamperometry

Chronoamperometry is the process of providing a constant voltage to a working electrode and measuring the resulting current over time. It is useful for determining reaction kinetics and detecting trace analytes in pharmaceutical samples. This approach is frequently used in conjunction with flow injection analysis for high-throughput screening [55,56].

4.3.2. Flow Injection Analysis

Flow injection analysis combines amperometry and a flow system to enable rapid and automated analysis of pharmaceutical samples. This is especially beneficial for high-throughput screening and quality control, allowing the analysis of several samples in a short period [57,58].

5. Practical Applications

Electroanalysis is an indispensable tool in the pharmaceutical industry, offering high sensitivity, selectivity, and rapid response times for various analytical applications [59,60]. Its versatility allows for the precise measurement of drug compounds, impurities, and metabolic byproducts. Some key applications of electroanalysis in the pharmaceutical sector are listed in Table 1.
Drug Discovery and Development—Electroanalytical techniques aid in screening potential drug candidates by evaluating their redox properties, stability, and bioavailability, thereby accelerating the early-stage development process.
Quality Control and Assurance—Differential pulse voltammetry and related techniques enable the precise quantification of active pharmaceutical ingredients (APIs) and the detection of impurities, ensuring compliance with regulatory standards.
Pharmacokinetics and Metabolism Studies—Real-time monitoring of drug and metabolite concentrations in biological fluids using amperometric biosensors provides critical data for determining optimal dosage regimens and administration routes.
Therapeutic Drug Monitoring (TDM)—Electroanalytical methods facilitate personalized medicine by continuously tracking patient drug levels, optimizing treatment effectiveness, and minimizing adverse effects.
Environmental Monitoring—The detection of pharmaceutical residues in environmental samples, such as wastewater and surface water, is crucial for assessing their ecological impact. Square wave voltammetry allows for the highly sensitive identification of trace contaminants.
Counterfeit Drug Detection: Electroanalysis offers a rapid and reliable approach for counterfeit drug detection by identifying variations in active pharmaceutical ingredients (APIs) and excipients through electrochemical fingerprinting. Portable electrochemical sensors further enable on-site testing, aiding regulatory bodies and pharmacies in ensuring drug authenticity and patient safety [61].
Table 1. Various properties of electroanalytical methods.
Table 1. Various properties of electroanalytical methods.
S. No.PropertiesElectroanalytical MethodApplicationRef.
1.Drug Development and ResearchCyclic Voltammetry (CV)Characterizing redox properties of drug candidates[62]
Electroanalytical ScreeningIdentifying potential drug candidates
2.Quality Control and AssuranceDifferential Pulse Voltammetry (DPV) and Square Wave Voltammetry (SWV)Determining APIs in pharmaceutical formulations[63]
ElectroanalysisDetecting impurities and degradation products
3.Pharmacokinetics and Drug MetabolismElectrochemical SensorsMonitoring drug metabolism in biological fluids[64]
ElectroanalysisAssessing drug bioavailability in plasma and tissues
4.Therapeutic Drug Monitoring (TDM)Electrochemical SensorsReal-time monitoring of drug levels in patients[65]
Electrochemical DevicesPoint-of-care testing for rapid drug measurement
5.Environmental MonitoringElectroanalysisDetecting pharmaceutical residues in environmental samples[66]
6.Counterfeit Drug DetectionElectrochemical TechniquesAuthenticating pharmaceuticals and detecting counterfeit drugs
7.Electrochemical BiosensorsEnzyme-Based SensorsDetecting drug molecules and metabolites[67]
8.Electrochemical Impedance Spectroscopy (EIS)EISStudying drug-target interactions (proteins, DNA)[68]
EISCharacterizing drug delivery systems (nanoparticles, hydrogels)
Real-world Examples in Drug Analysis
9.Detection of Pharmaceutical CompoundsCyclic Voltammetry (CV)Detecting paracetamol in tablets and biological fluids[69]
Differential Pulse Voltammetry (DPV)Detecting propranolol in pharmaceutical tablets
10.Analysis of AntibioticsSquare Wave Voltammetry (SWV)Determining ciprofloxacin in milk samples[70]
Amperometric Detection (with HPLC)Analyzing amoxicillin in urine samples
11.Analysis of Illicit DrugsElectrochemical SensorsOn-site detection of cocaine and methamphetamine[71]
Potentiometric MethodsMeasuring morphine metabolites in urine samples
12.Quality Control in Drug ManufacturingElectrochemical Impedance Spectroscopy (EIS)Studying drug release profiles in controlled-release tablets[72]
ChronoamperometryMonitoring degradation and stability of pharmaceutical compounds

5.1. Drug Development and Research

5.1.1. Electrochemical Characterization in Drug Development

Electrochemical techniques, such as cyclic voltammetry (CV), are pivotal in assessing the redox properties of drug candidates. By analyzing electron transfer reactions, CV provides valuable insights into the stability, reactivity, and metabolic fate of a compound [73].
Key Applications of Cyclic Voltammetry in Pharmaceuticals:
(i)
Stability Assessment—CV helps determine whether a drug candidate undergoes oxidation or reduction under physiological conditions, predicting its shelf life and degradation pathways.
(ii)
Reactivity and Mechanism Studies—Understanding a molecule’s electrochemical behavior allows researchers to evaluate its interaction with biological targets and predict possible side reactions that could affect its efficacy.
(iii)
Metabolic Pathway Prediction—Many drug metabolism processes involve oxidation or reduction, often mediated by enzymes like cytochrome P450. CV mimics these redox reactions and offers insights into the potential metabolic products and their biological activities.
(iv)
Structure-Activity Relationship (SAR) Analysis—Electrochemical data can be correlated with a drug’s pharmacological properties, aiding in the rational design of more effective and stable pharmaceutical compounds.
(v)
Drug Formulation and Delivery Optimization—By studying the electrochemical behavior, researchers can modify formulations to enhance solubility, bioavailability, and targeted drug release. Cyclic voltammetry and complementary electroanalytical techniques significantly enhance drug characterization, contributing to the development of safer and more effective therapeutics [74].

5.1.2. Screening of Drug Compounds Using Electroanalytical Methods

Electroanalytical techniques are powerful tools for the high-throughput screening of drug libraries, enabling the rapid identification of compounds with desirable electrochemical properties. These methods provide critical insights into the redox behavior, stability, and interactions of drug candidates with biomolecules, which are essential for assessing their pharmacological potential [75].
Key Advantages of Electroanalytical Screening in Drug Discovery:
(i)
Rapid Identification of Active Compounds—Electrochemical techniques, such as CV and DPV, allow for the quick assessment of redox-active compounds, helping to narrow down promising drug candidates from large molecular libraries.
(ii)
Prediction of Pharmacokinetics and Metabolism—Many drugs undergo oxidation or reduction during metabolism. Screening for electrochemical activity helps predict how a compound will be processed in vivo, aiding drug design and optimization.
(iii)
Cost-Effective and High-Throughput Analysis—Compared to conventional biological assays, electroanalytical methods provide a faster and more economical approach for evaluating drug properties, making them ideal for early-stage screening.
(iv)
Assessment of Drug Stability—By analyzing oxidation-reduction potentials, researchers can determine a compound’s susceptibility to degradation, ensuring the selection of chemically stable candidates.
(v)
Environmental and Toxicity Profiling—Electrochemical screening can also help identify potentially toxic compounds or those prone to environmental persistence, contributing to safer drug development. By integrating electroanalytical methods into drug discovery workflows, pharmaceutical researchers can efficiently evaluate large compound libraries, thereby accelerating the development of effective and safe therapeutic agents [76].

5.2. Quality Control and Assurance

Ensuring the quality, purity, and stability of pharmaceutical products is critical for regulatory compliance and ensuring patient safety. Electroanalytical techniques, such as DPV and SWV, offer highly sensitive, selective, and cost-effective methods for quality control by quantifying active pharmaceutical ingredients (APIs) and detecting impurities or degradation products [77].
(i)
Determination of Active Pharmaceutical Ingredients (APIs)
Electroanalytical methods are widely used to measure the concentrations of APIs in drug formulations to ensure that they meet the specified dosage requirements.
DPV and SWV for Precise Quantification—These techniques provide high sensitivity and resolution, enabling accurate measurement of API concentrations, even in complex formulations.
Rapid and Non-Destructive Analysis—Compared to chromatographic techniques, electroanalysis offers faster and often non-destructive analysis, thereby reducing time and cost.
Real-Time Monitoring—Some electrochemical sensors allow continuous monitoring of APIs in liquid formulations, ensuring consistency throughout production.
(ii)
Detection of Impurities and Degradation Products
Electroanalytical techniques play a crucial role in assessing pharmaceutical purity by identifying trace levels of contaminants and degradation products that may impact drug safety and efficacy.
Early Detection of Degradation Pathways—Electroanalysis helps monitor oxidation-reduction reactions that could lead to drug instability, allowing for improved formulation strategies.
Identification of Toxic Impurities—Many impurities arise from raw materials or production processes. Electrochemical techniques can detect even minute concentrations of these substances, ensuring compliance with the pharmacopeial standards.
Enhanced Sensitivity Over Traditional Methods—Techniques such as stripping voltammetry enable the detection of extremely low concentrations of metal ions and other electroactive contaminants.
By integrating electroanalytical methods into pharmaceutical quality control, manufacturers can ensure that drug products remain safe, effective, and compliant with industry regulations while optimizing production efficiency [78].

5.3. Pharmacokinetics and Drug Metabolism

Electroanalytical techniques play a vital role in pharmacokinetic and drug metabolism studies by enabling precise real-time monitoring of drug concentrations and metabolic transformations in biological systems. These methods provide critical data for optimizing dosage regimens, improving bioavailability, and ensuring therapeutic efficacy [79].
(i)
Monitoring Drug Metabolism
Understanding how drugs are metabolized in the body is essential for predicting their efficacy and potential side effects. Electrochemical sensors offer a powerful means of detecting and quantifying drug metabolites in biological fluids, such as blood, urine, and saliva.
Real-Time Detection—Amperometric and potentiometric biosensors allow continuous tracking of metabolite levels, offering insights into drug clearance and biotransformation pathways.
Selective and Sensitive Analysis—Electroanalytical methods can distinguish between parent drugs and their metabolites, even at low concentrations, thereby aiding in metabolic profiling.
Non-Invasive Monitoring—Electrochemical sensors can be integrated into wearable devices for real-time pharmacokinetic studies, reducing the need for invasive sampling [80].
(ii)
Bioavailability Studies
The bioavailability of a drug, which is its ability to reach the systemic circulation in an active form, directly affects its therapeutic performance. Electroanalytical techniques provide a rapid and reliable means of measuring drug concentrations in the plasma and tissues.
Precision in Quantification—Techniques such as DPV and SWV enable the accurate quantification of drugs in biological samples, helping to assess their absorption and distribution.
Enhanced Drug Formulation—By analyzing drug release profiles in various formulations, electroanalysis assists in optimizing controlled-release and targeted-delivery systems.
Evaluation of Drug Interactions—Electroanalytical studies can reveal how co-administered drugs affect metabolism and bioavailability, ensuring safe and effective combination therapies.
By integrating electroanalytical techniques into pharmacokinetic research, pharmaceutical scientists can enhance drug development processes, personalize dosing regimens and improve therapeutic outcomes [81].

5.4. Therapeutic Drug Monitoring (TDM)

TDM is essential for optimizing drug therapy, ensuring that patients receive the correct dosage, while minimizing adverse effects. Electroanalytical methods, particularly portable and wearable electrochemical sensors, have revolutionized TDM by enabling real-time, on-site monitoring of drug concentrations in biological fluids [82].
(i)
Real-Time Monitoring of Drug Levels
Advancements in electrochemical sensor technology have enabled continuous and non-invasive monitoring of drug levels in patients, leading to personalized and precision medicine.
Wearable Biosensors for Dynamic Tracking—Miniaturized electrochemical sensors can be integrated into wearable devices, such as smart patches, to continuously monitor drug concentrations in sweat, saliva, and interstitial fluids.
Prevention of Toxicity and Underdosing—Real-time tracking helps maintain drug levels within the therapeutic window, preventing toxic accumulation or subtherapeutic dosing.
Automated Drug Dosing Adjustments—Electroanalytical data can be integrated into AI-driven systems to dynamically adjust dosing regimens, ensuring optimal treatment outcomes [83].
(ii)
Point-of-Care Testing (POCT)
Electrochemical devices are widely used in clinical and bedside settings to provide rapid and accurate drug level assessments, facilitating immediate treatment decisions.
Fast and Cost-Effective Analysis—Unlike traditional laboratory-based assays, electrochemical point-of-care devices offer rapid results within minutes, reducing the waiting time for critical therapeutic adjustments.
User-Friendly and Portable Technology—Handheld and disposable electrochemical sensors allow drug monitoring in outpatient, home-care, and emergency settings, increasing accessibility for patients with chronic conditions.
Clinical Applications in Various Therapeutic Areas—Electrochemical POCT devices are especially useful for monitoring drugs with narrow therapeutic indices, such as antibiotics, anticoagulants, immunosuppressants, and chemotherapeutic agents.
By integrating electroanalytical methods into TDM, healthcare providers can enhance treatment precision, improve patient adherence, and reduce the risk of adverse drug reactions, ultimately leading to improved clinical outcomes [84].

5.5. Environmental Monitoring Using Electroanalytical Techniques

The presence of pharmaceutical residues in the environment poses significant risks to ecosystems and public health. Electroanalytical methods provide highly sensitive, selective, and cost-effective solutions for detecting and quantifying pharmaceutical contaminants in various environmental matrices, including water, soil, and sediments.
(i)
Detection of Pharmaceutical Residues in Environmental Samples
Electroanalysis plays a crucial role in assessing the environmental impact of pharmaceutical compounds by enabling the precise and real-time detection of drug residues.
Water Quality Monitoring—Electrochemical sensors and voltammetric techniques, such as SWV and DPV, allow for the trace-level detection of pharmaceutical contaminants in surface water, groundwater, and wastewater.
Soil and Sediment Analysis—Adsorptive stripping voltammetry (AdSV) and modified electrodes help analyze pharmaceutical residues in soil, revealing their persistence, degradation rates, and potential bioaccumulation in ecosystems.
Real-Time and On-Site Detection—Portable electrochemical sensors facilitate rapid, in-field analysis, reducing the need for complex sample preparation and laboratory testing [85].
(ii)
Ensuring Compliance with Environmental Regulations
Pharmaceutical pollution is a growing concern, leading to strict environmental regulations to limit the presence of drug residues in water bodies and agricultural lands. Electroanalytical methods contribute to regulatory compliance by
Monitoring Discharges from Pharmaceutical Industries—Electrochemical techniques help assess the effectiveness of wastewater treatment plants in removing pharmaceutical pollutants.
Detecting Persistent Pollutants—Some pharmaceutical compounds, such as antibiotics and hormones, exhibit long-term environmental persistence. Electroanalysis helps to track degradation and transformation products.
Supporting Green Chemistry Initiatives—By identifying and monitoring pharmaceutical residues, electroanalytical methods assist in the development of eco-friendly drug formulations and sustainable waste management strategies.
By integrating electroanalytical techniques into environmental monitoring programs, regulatory agencies, and researchers can ensure safer water resources, reduce pharmaceutical pollution, and improve ecological sustainability [86].

5.6. Counterfeit Drug Detection Using Electroanalytical Techniques

The increase in counterfeit pharmaceuticals poses a significant threat to public health, leading to ineffective treatments and potentially fatal outcomes. Electroanalytical techniques offer a rapid, sensitive, and cost-effective solution for authenticating drugs by detecting variations in their electrochemical signatures.
(i)
Authentication of Pharmaceuticals
Electrochemical methods can distinguish between genuine and counterfeit medications based on differences in their active pharmaceutical ingredients (APIs), excipients, and formulation composition.
Electrochemical Fingerprinting—Techniques such as DPV and CV generate unique electrochemical signatures for authentic drugs, allowing quick comparison with suspected counterfeits.
Detection of Missing or Altered APIs—Counterfeit drugs often lack the correct API concentration or contain harmful substitutes. Electroanalysis enables the precise quantification of APIs, ensuring compliance with pharmaceutical standards.
Analysis of Excipients and Additives—Electroanalytical methods can also identify non-active ingredients and contaminants, which may indicate substandard or counterfeit production [87].
(ii)
Rapid and Portable Screening for Law Enforcement and Pharmacies
Electrochemical sensors and portable devices provide on-site drug authentication, aiding regulatory authorities, pharmacists, and healthcare providers in real-time counterfeit detection.
Point-of-Care and Field Testing—Handheld electrochemical devices enable drug verification at customs checkpoints, pharmacies, and distribution centers, reducing the circulation of fake medicines.
Minimal Sample Preparation—Unlike chromatographic methods, electroanalysis requires little to no sample processing, making it an efficient and user-friendly technique for rapid screening.
Affordable and Scalable Solutions—Electrochemical methods provide a cost-effective alternative to complex laboratory-based techniques, making large-scale counterfeit drug detection more feasible, especially in low-resource settings [88].
By integrating electroanalytical techniques into counterfeit drug surveillance, authorities can enhance pharmaceutical security, protect patients from harmful medications, and strengthen global efforts to combat drug fraud.
Therapeutic drug monitoring (TDM) is essential for optimizing drug therapy and ensuring that patients receive the correct dosage while minimizing adverse effects. Electroanalytical methods, particularly portable and wearable electrochemical sensors, have revolutionized TDM by enabling real-time, on-site monitoring of drug concentrations in biological fluids [89].

5.7. Real-World Examples in Drug Analysis

Electroanalytical techniques are widely used in drug analysis due to their sensitivity, selectivity, and rapid response. Here are some real-world examples of how these techniques are applied:

5.7.1. Detection of Pharmaceutical Compounds

  • Cyclic Voltammetry (CV): This technique is applied to detect and quantify pharmaceutical compounds, such as paracetamol (acetaminophen), in dosage forms and biological fluids. This technique provides high sensitivity and accuracy, allowing for effective monitoring of drug concentration.
  • Differential Pulse Voltammetry (DPV): Employed for the analysis of drugs like propranolol, a beta-blocker used in treating hypertension. DPV was used to detect propranolol in pharmaceutical tablets. This method offers high selectivity and sensitivity, allowing the drug to be distinguished from other substances in a sample [90].

5.7.2. Analysis of Antibiotics

  • Square Wave Voltammetry (SWV): This technique is used to determine antibiotic residues in food products and biological samples. SWV has been used to detect ciprofloxacin, an antibiotic, in milk samples. This technique provides rapid and accurate results, ensuring food safety and compliance with regulatory standards.
  • Amperometric Detection: This method is used with liquid chromatography to determine antibiotics in pharmaceutical formulations and biological fluids. Amperometric detection was coupled with high-performance liquid chromatography (HPLC) to analyze amoxicillin in urine samples. This combined approach enhances the sensitivity and precision of the measurements [91].

5.7.3. Analysis of Illicit Drugs

  • Electrochemical Sensors: Portable electrochemical sensors are used for the on-site detection of illicit drugs, such as cocaine and methamphetamine. An electrochemical sensor was developed to detect cocaine in banknotes. The sensor provides rapid, non-destructive testing, enabling law enforcement agencies to quickly identify contaminated currency.
  • Potentiometric Methods: Used for the determination of drug metabolites in biological fluids. Potentiometric ion-selective electrodes were used to measure the concentrations of morphine metabolites in the urine samples. This technique offers high specificity and ease of use, making it suitable for both clinical and forensic applications [92].

5.7.4. Quality Control in Drug Manufacturing

  • Electrochemical Impedance Spectroscopy (EIS): Used for the characterization of drug release profiles in pharmaceutical formulations. EIS was used to study the release of a drug from a polymer matrix in controlled-release tablets. This technique provides detailed information on the drug release mechanisms and kinetics.
  • Chronoamperometry: Used to monitor the electrochemical stability and degradation of pharmaceutical compounds. Chronoamperometry was employed to investigate the stability of ascorbic acid (vitamin C) in a pharmaceutical formulation. This method allows for real-time monitoring of degradation processes, ensuring product quality and shelf life. Table 2 lists the methods and applications of electroanalysis in drug analysis.

5.8. Comparative Studies with Other Analytical Methods

Electroanalysis is often compared with other analytical methods like spectrophotometry, chromatography, and mass spectrometry. Each technique has its strengths and weaknesses, depending on the specific application [59]. Table 3 and Table 4 depict the detailed comparative studies between electroanalytical methods and other analytical techniques in drug analysis [95,96].
  • Cyclic Voltammetry (CV): CV is often employed in the initial stages of method development due to its ability to elucidate the redox behavior of paracetamol. While it offers valuable mechanistic insights, its sensitivity is moderate, making it less suitable for detecting low concentrations.
  • Differential Pulse Voltammetry (DPV): DPV enhances sensitivity by applying a series of voltage pulses, allowing the detection of paracetamol at trace levels. Its high selectivity minimizes interference from other substances, making it ideal for use in complex matrices.
  • Square Wave Voltammetry (SWV): SWV combines rapid analysis with high sensitivity, making it effective in environments with significant background noise. Its ability to discriminate capacitive currents enhances the detection of paracetamol in various samples.
  • Amperometric Detection: This technique is advantageous for continuous monitoring applications, such as flow systems or biosensors. Its very high sensitivity enables the detection of paracetamol at very low concentrations. However, it may suffer from interference from other electroactive species present in the sample.
  • Electrochemical Impedance Spectroscopy (EIS): EIS is valuable for characterizing electrode surfaces and understanding interfacial phenomena. While not typically used for the direct quantification of paracetamol, it plays a crucial role in developing and optimizing electrochemical sensors for its detection. The choice of electroanalytical method for detecting paracetamol depends on the specific requirements of the analysis, including the desired sensitivity, selectivity, sample matrix, and available instrumentation. For instance, DPV and SWV are preferred for trace analysis due to their high sensitivity, whereas amperometric detection is suitable for real-time monitoring applications. Understanding the unique capabilities of each technique ensures the selection of the most appropriate method for the accurate and reliable detection of pharmaceuticals like paracetamol.

6. Advancements in Electroanalysis for Pharmaceuticals

Recent advancements in electroanalysis of pharmaceuticals have significantly enhanced the detection, quantification, and monitoring of drug compounds. Innovations in electrode materials, such as the development of nanostructured electrodes and carbon-based nanomaterials, have substantially improved their sensitivity and selectivity. These advanced electrodes can detect lower concentrations of pharmaceutical compounds, making them particularly valuable for trace analysis and therapeutic drug monitoring [103]. Additionally, the integration of electrochemical sensors with microfluidic devices has enabled the creation of lab-on-a-chip systems, allowing rapid on-site drug analysis with minimal sample volumes and reduced analysis times. The coupling of electroanalytical techniques with advanced data processing algorithms, including machine learning and artificial intelligence, has further enhanced the interpretation of complex electrochemical signals, improving the accuracy and reliability of drug detection. Moreover, the development of portable and wearable electrochemical devices has expanded the applications of electroanalysis to point-of-care testing and personalized medicine, providing real-time monitoring of drug levels in patients. These advancements are driving the field toward more efficient, cost-effective, and user-friendly solutions for pharmaceutical analysis, ultimately contributing to better healthcare outcomes [104].

6.1. Recent Technological Developments

Recent technological developments in electroanalysis have revolutionized various scientific and industrial fields by enhancing the precision, sensitivity, and applicability of electrochemical measurements. Advances in nanotechnology have led to the development of nanostructured electrodes, including those made of graphene, carbon nanotubes, and metal nanoparticles. These nanomaterials offer significantly increased surface areas, leading to enhanced electron transfer rates and improved detection limits for a wide range of analytes. Additionally, the integration of microfluidic technology with electroanalytical devices has paved the way for the development of sophisticated lab-on-a-chip systems. These systems facilitate the miniaturization and automation of complex analytical procedures, enabling rapid and efficient analyses with minimal sample and reagent consumption [13]. The incorporation of digital technologies, such as machine learning algorithms and artificial intelligence, into electroanalytical systems has also markedly improved data processing and interpretation. These technologies enable real-time high-throughput analysis and provide deeper insights into complex electrochemical processes. Furthermore, the advent of wearable and portable electrochemical sensors has expanded the scope of electroanalysis to include the continuous monitoring of environmental and biological parameters, making it possible to perform in situ analyses in real-time. These technological advancements are driving the evolution of electroanalysis into a more versatile, efficient, and accessible field with broad implications for environmental monitoring, healthcare, food safety, and pharmaceuticals [105].

6.2. Integration with Other Analytical Techniques

The integration of electroanalysis with other analytical techniques has opened new avenues for enhancing the accuracy, sensitivity, and comprehensiveness of the analytical results. Combining electroanalytical methods with chromatographic techniques, such as high-performance liquid chromatography (HPLC) and gas chromatography (GC), allows for the separation of complex mixtures, followed by sensitive electrochemical detection (Table 5). This hybrid approach is particularly effective in pharmaceutical analysis, where it can differentiate and quantify various drug compounds and their metabolites in biological samples with high precision. Incorporating mass spectrometry (MS) with electroanalysis, known as electrochemical mass spectrometry (EC-MS), offers detailed structural information and high sensitivity. This integration facilitates the identification of electrochemically active species and their reaction mechanisms, providing a comprehensive understanding of the redox processes in drug compounds [106].
Furthermore, the combination of electroanalysis with spectroscopic techniques, such as UV-Vis and fluorescence spectrophotometry, enhances the detection capabilities of compounds that may not exhibit strong electrochemical signals alone. For instance, the coupling of electrochemiluminescence (ECL) with fluorescence spectroscopy enables the detection of trace amounts of analytes with improved selectivity and sensitivity. The integration of microfluidic devices has led to the expansion of lab-on-a-chip systems that combine multiple analytical techniques on a single platform. These systems can perform sample preparation, separation, and detection in a streamlined and automated manner, reducing the sample volume and analysis time while increasing the throughput [107].
Overall, the synergistic integration of electroanalysis with other analytical techniques provides a multifaceted approach to chemical analysis, leveraging the strengths of each method to overcome the individual limitations. This integration enhances the robustness, efficiency, and scope of analytical capabilities in various fields, including pharmaceuticals, environmental monitoring, and biomedical research. This integration enhances the analytical capabilities by combining the sensitivity of electroanalysis to redox processes with the specificity and detection strength of other techniques.
Table 5. Integration of electroanalysis with other analytical techniques.
Table 5. Integration of electroanalysis with other analytical techniques.
S. No.Analytical TechniqueElectroanalysis IntegrationApplicationsRef.
1.Spectroscopy (UV-Vis, IR, Raman, etc.)Electrochemical methods can provide information about redox states, which complements spectroscopic data.Identification of electroactive species, monitoring reaction kinetics, studying redox properties.[70]
2.Mass Spectrometry (MS)Coupling electroanalysis with MS allows real-time monitoring of electrochemical reactions and the identification of products.Detection of reaction intermediates and products, studying reaction mechanisms.
3.Chromatography (HPLC, GC)Electrochemical detectors are often used after chromatographic separation to detect analytes that are electroactive.Separation and quantification of trace analytes, detection of pollutants in environmental analysis.[108]
4.Atomic Absorption Spectroscopy (AAS)Electrochemical pretreatment can concentrate analytes for enhanced detection by AAS.Trace metal analysis, improving detection limits in metal ion quantification.
5.X-ray Diffraction (XRD)Electrochemical processes can alter the structure of materials, which can then be studied using XRD to observe changes in crystallinity.Characterization of electrode materials, study of phase changes during electrochemical cycling.[109]
6.Thermogravimetric Analysis (TGA)Electrochemical reactions can be studied with TGA to observe weight changes corresponding to redox reactions and material decomposition.Studying degradation of battery materials, analysis of oxidation/reduction mechanisms.[110]
7.Nuclear Magnetic Resonance (NMR)Electroanalysis can alter the chemical environment, providing insight into changes that can be analyzed via NMR.Studying the structure of electroactive molecules and understanding molecular interactions during redox reactions.[111]
8.Microscopy (SEM, TEM, AFM)Electrochemical techniques are combined with microscopy to visualize changes in surface morphology during reactions.Monitoring electrode surface changes, studying corrosion, material science applications.[112]
9.Capillary Electrophoresis (CE)Electrochemical detectors can be coupled with CE for the detection of electroactive species after electrophoretic separation.Separation and detection of biomolecules, drugs, and ions.
10.Fluorescence SpectroscopyFluorescent molecules can be used as probes in electrochemical systems to monitor redox processes in real-time.Biosensing applications, detection of specific ions and molecules, bioimaging of electroactive species.
11.Spectroelectrochemistry (SEC) Electrochemical techniques are coupled with spectroscopic methods (UV-Vis, IR, Raman) to monitor electrochemical reactions and their corresponding spectral changes simultaneously.Identification of redox states, tracking reaction intermediates, real-time monitoring of charge transfer mechanisms in pharmaceuticals and biomolecules.[113]
12.Voltabsorptometry (VA)Correlates voltammetric data with optical absorption measurements to analyze changes in electronic states during redox reactions.Characterization of electroactive compounds, study of oxidation-reduction processes, evaluation of molecular stability under electrochemical conditions.
Despite this table, the following well-structured paragraph can be included in the Methods section to clarify the role of spectroelectrochemistry and voltabsorptometry in your study: Spectroelectrochemistry and voltabsorptometry were employed to gain deeper insights into the electrochemical behavior of the studied compounds by combining electrochemical and spectroscopic techniques. Spectroelectrochemistry integrates optical absorption measurements with electrochemical analysis, allowing real-time monitoring of changes in the oxidation states and electronic transitions during redox processes. This method enhances the sensitivity and selectivity for identifying intermediate species and reaction mechanisms. Similarly, voltabsorptometry, which correlates voltammetric data with absorption spectra, provides valuable information on charge transfer dynamics and molecular interactions. These techniques were chosen to improve the accuracy of electroanalytical measurements, particularly for characterizing complex redox-active molecules. Their application is crucial in pharmaceutical and bioanalytical studies, where precise detection and mechanistic understanding of electrochemical processes are essential [113].

6.3. Innovations in Sensor Materials and Design

Innovations in sensor materials and design have significantly advanced the field of electroanalysis, enhancing the sensitivity, selectivity, and versatility of electrochemical sensors. Key developments in this area include the use of nanomaterials, the creation of novel electrode architectures, and the integration of flexible and wearable sensor designs.
Nanomaterials: The introduction of nanomaterials, such as graphene, carbon nanotubes, metal nanoparticles, and quantum dots, has revolutionized sensor performance. These materials offer exceptional electrical conductivity, large surface areas, and unique electrochemical properties, which improve electron transfer rates and enhance detection limits for various analytes. For example, graphene-based sensors have demonstrated superior sensitivity and stability in detecting pharmaceutical compounds and biomarkers [114].
Composite and Hybrid Materials: Combining different nanomaterials into composite structures has further enhanced sensor functionality. For instance, incorporating metal nanoparticles into carbon-based materials creates hybrid electrodes with synergistic properties, such as increased catalytic activity and improved signal-to-noise ratios. These hybrid sensors are particularly effective for complex sample matrices, where high selectivity and sensitivity are crucial.
Molecularly Imprinted Polymers (MIPs): MIPs are synthetic polymers with molecular recognition sites tailored to specific target molecules. These polymers enhance the selectivity of electrochemical sensors by providing a highly specific binding environment for the analyte. MIP-based sensors are widely used to detect drugs, environmental pollutants, and biomolecules and offer robust performance even under challenging conditions.
Flexible and Wearable Sensors: Advancements in materials science have facilitated the development of flexible and wearable electrochemical sensors. These sensors are made from stretchable and biocompatible materials, such as conductive polymers and flexible substrates, allowing them to conform to the skin or other surfaces. Wearable sensors can continuously monitor physiological parameters, such as glucose levels and sweat metabolites, providing real-time health data for personalized medicine.
Micro and Nano-fabrication Techniques: Innovations in fabrication techniques, including photolithography, screen printing, and 3D printing, have facilitated the production of miniaturized and integrated sensor systems. These techniques allow precise control over the sensor design, enabling the creation of multi-analyte sensors and lab-on-a-chip devices. These devices can perform complex analyses with high throughput and minimal sample volumes.
Self-Powered Sensors: The development of self-powered electrochemical sensors, which harvest energy from their environment (e.g., biofuel cells or triboelectric nanogenerators), has opened new possibilities for remote and long-term monitoring applications. These sensors operate without external power sources, making them ideal for environmental monitoring and as implantable medical devices.
In summary, innovations in sensor materials and design have dramatically expanded the capabilities of electroanalytical techniques. These advancements have led to the creation of highly sensitive, selective, and versatile sensors, enabling more accurate and efficient analyses in diverse fields, such as healthcare, environmental monitoring, and pharmaceuticals [115].

7. Challenges and Limitations

Electroanalysis faces several challenges and limitations that impact its effectiveness and reliability. One significant issue is electrode fouling, in which the electrodes become coated with reaction products or contaminants, reducing their sensitivity and accuracy over time. Interference from other electroactive species in the sample can lead to overlapping signals and inaccurate measurements. Complex sample matrices, which are common in biological, environmental, and industrial samples, further complicate the isolation and measurement of specific analytes. Reproducibility and stability are also concerns due to variability in electrode preparation and environmental conditions, which affect consistency and reliability. The detection limits are constrained by noise and background currents, making it difficult to detect analytes at low concentrations (Table 6). Additionally, kinetic and mass transport limitations can hinder the rate of electrochemical reactions, affecting the speed and efficiency of the analysis. Achieving high selectivity is challenging because similar species can interfere with the target analyte, leading to inaccurate quantification. The cost and complexity of advanced electroanalytical instruments limit their accessibility, particularly in resource-limited settings. Environmental factors, such as temperature, pH, and ionic strength, also influence electrochemical measurements, contributing to variability in the results. Lastly, characterizing and controlling the surface properties of electrodes is difficult, affecting reproducibility and sensitivity. Addressing these challenges requires the optimization of experimental conditions, development of new materials and techniques, and a deep understanding of electrochemical processes. Electroanalysis, which involves the use of electrochemical methods to study chemical systems, offers powerful tools for chemical analysis and sensor development. However, it also faces several challenges and limitations.

7.1. Sensitivity and Selectivity Issues

In electroanalysis, sensitivity and selectivity are crucial for accurately detecting and quantifying specific analytes; however, both face significant challenges. Sensitivity issues arise from background noise and currents, which can obscure signals from low-concentration analytes, making detection difficult. Electrode fouling, in which reaction products or contaminants accumulate on the electrode surface, further diminishes the sensitivity over time. Additionally, mass transport limitations and suboptimal electrode surface area or morphology can hinder the response by limiting the rate of the electrochemical reactions. Selectivity issues, on the other hand, stem from the presence of interfering species that produce overlapping signals, leading to inaccurate measurements and false positives. Complex sample matrices, which are common in biological, environmental, and industrial contexts, complicate the isolation and accurate measurement of target analytes. Cross-reactivity among similar species can also cause misidentification and inaccurate quantification. While electrode modifications can enhance selectivity, they can sometimes negatively impact other properties like sensitivity and stability. To address these challenges, optimizing electrode materials, surface modifications, and experimental conditions is essential, with advances in nanotechnology and sensor design playing a key role in improving both sensitivity and selectivity of electroanalytical methods [121].

7.2. Regulatory and Standardization Challenges

Electroanalysis faces regulatory and standardization challenges that impact its adoption and reliability across various industries. Regulatory bodies require stringent validation and compliance with performance standards, which can be difficult to achieve due to the inherent variability in electrode preparation and environmental conditions affecting reproducibility. The lack of universally accepted protocols and calibration standards complicates comparisons between different studies and devices, making it difficult to establish consistency and trust in electroanalytical measurements. Furthermore, diverse application areas, from environmental monitoring to biomedical diagnostics, each demand specific standards and regulatory approvals, adding to the complexity. The rapid pace of technological advancements in materials and techniques often outstrips the development of corresponding regulatory frameworks, leading to gaps in oversight and potential delays in the approval of new methods. Addressing these challenges necessitates collaborative efforts between researchers, industry stakeholders, and regulatory agencies to develop standardized protocols, robust validation procedures, and comprehensive regulatory guidelines that ensure the accuracy, reliability, and safety of electroanalytical methods [122].

8. Future Perspectives

Electroanalysis is rapidly evolving, with several emerging trends that are poised to significantly impact drug development, manufacturing, and personalized medicine. One notable trend is the integration of nanotechnology, which enhances the sensitivity and selectivity of electrochemical sensors through the use of nanostructured materials like nanoparticles, nanotubes, and graphene. These materials increase the surface area and improve electron transfer rates, enabling the detection of lower concentrations of analytes with greater precision. Another key trend is the development of miniaturized and portable electroanalytical devices, such as lab-on-a-chip systems and wearable sensors. These innovations facilitate on-site and real-time monitoring, which is particularly beneficial for high-throughput screening in drug development and continuous monitoring of critical parameters during manufacturing processes. Advancements in bioelectrochemical sensors, which incorporate biological elements like enzymes, antibodies, or nucleic acids, are also driving progress. These biosensors offer high specificity and sensitivity for detecting biomolecules, making them valuable tools for studying biochemical pathways, drug interactions, and the pharmacokinetics of new therapeutics. The integration of artificial intelligence (AI) and machine learning (ML) with electroanalysis is another transformative trend. AI and ML algorithms can analyze complex datasets, identify patterns, and predict outcomes, thereby enhancing the interpretation of electrochemical data and optimizing the experimental conditions. This integration can accelerate the drug discovery process by enabling more efficient screening of potential drug candidates and a better understanding of their mechanisms of action [123]. Electroanalysis is poised to play a crucial role in personalized medicine by facilitating the development of customized diagnostic and therapeutic approaches tailored to an individual’s unique biochemical profile. A key application of this technology is the development of point-of-care (POC) diagnostic devices, which offer rapid and precise measurements of biomarkers. These devices can be used to monitor disease progression, therapeutic responses, and drug levels in the body, allowing timely adjustments to treatment regimens. Electrochemical sensors can also be employed to analyze genetic and metabolic markers, facilitating the customization of treatments based on a patient’s genetic makeup and metabolic state [84]. For instance, electroanalysis can be used to detect single nucleotide polymorphisms (SNPs) or to measure metabolites that influence drug metabolism, thereby helping to predict patient-specific drug efficacy and toxicity. Moreover, continuous glucose monitors (CGMs) and other wearable electrochemical sensors exemplify the potential of electroanalysis for managing chronic conditions. These devices provide real-time data that can be used to personalize treatment plans, improve patient compliance and enhance overall health outcomes. In drug development, electroanalytical techniques can be utilized to screen patient-derived cells or tissues for drug responses, enabling the identification of the most effective treatment for individual patients. This approach not only increases the likelihood of therapeutic success but also reduces the risk of adverse effects by tailoring interventions to the patient’s specific biological context [124].

9. Conclusions

Electroanalysis is undergoing significant advancements that are expected to revolutionize the pharmaceutical industry and the field of personalized medicine. Key points include the integration of nanotechnology to enhance sensor sensitivity and selectivity, developing miniaturized and portable devices for real-time and on-site monitoring, and applying bioelectrochemical sensors for the specific and sensitive detection of biomolecules. Additionally, incorporating artificial intelligence and machine learning optimizes data interpretation and accelerates drug discovery processes. In the realm of personalized medicine, electroanalysis facilitates the development of point-of-care diagnostic devices and wearable sensors, enabling rapid and accurate biomarker measurements. These advancements are crucial for monitoring disease progression, therapeutic responses, and drug levels, allowing timely adjustments to treatment regimens. The ability to analyze genetic and metabolic markers further supports the customization of treatments based on individual patient profiles, enhancing drug efficacy and minimizing the adverse effects. The future of electroanalysis in pharmaceuticals looks exceptionally promising. Continued advancements in nanotechnology, bioelectrochemistry, and AI integration will further improve the performance and versatility of electroanalytical tools. These innovations are expected to play a critical role in high-throughput drug screening, real-time monitoring during manufacturing, and the personalization of medical treatments. As electroanalysis continues to evolve, it is poised to become an indispensable component of precision medicine, providing deeper insights into individual health and enabling more effective and personalized therapeutic interventions. This progress will ultimately lead to better patient outcomes, more efficient drug development processes, and a more personalized approach to healthcare. The future of electroanalysis in drug development and personalized medicine looks promising, driven by advancements in nanotechnology, miniaturization, bioelectrochemistry, and AI integration. These innovations enhance the sensitivity, selectivity, and portability of electroanalytical tools, making them indispensable for high-throughput drug screening, real-time monitoring, and customization of medical treatments. As the field evolves, electroanalysis will undoubtedly become a cornerstone of precision medicine, offering unprecedented insights into individual health and enabling more effective and personalized therapeutic interventions.

Author Contributions

Conceptualization and methodology, R.K. and S.S.; formal analysis, investigation, resources, data curation, R.K., S.S. and P.K.; writing—original draft preparation, R.K., S.S. and N.B.; writing—review and editing, supervision, B.K. and P.K. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Data Availability Statement

Not applicable.

Conflicts of Interest

The authors declare no conflict of interest.

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Figure 1. A simplified circuit for cyclic voltammetry. Where A is an Ammeter to measure the current (I) flowing through the circuit. V is a Voltmeter used to measure and control the potential difference (E) between the working and reference electrodes. Working Electrode is the electrode where the electrochemical reaction of interest occurs while Reference Electrode provides a stable reference potential against which the working electrode’s potential is controlled. Counter Electrode also known as the auxiliary electrode, completes the circuit and allows current to flow.
Figure 1. A simplified circuit for cyclic voltammetry. Where A is an Ammeter to measure the current (I) flowing through the circuit. V is a Voltmeter used to measure and control the potential difference (E) between the working and reference electrodes. Working Electrode is the electrode where the electrochemical reaction of interest occurs while Reference Electrode provides a stable reference potential against which the working electrode’s potential is controlled. Counter Electrode also known as the auxiliary electrode, completes the circuit and allows current to flow.
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Figure 2. Applications of electroanalysis in the pharmaceutical industry.
Figure 2. Applications of electroanalysis in the pharmaceutical industry.
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Table 2. Applications of electroanalysis in drug analysis.
Table 2. Applications of electroanalysis in drug analysis.
S. No.Electroanalysis MethodsAboutUsed ForRef.
1.Electrochemical Detection of Antibiotics
(Amoxicillin Detection using Modified Electrodes)
A glassy carbon electrode modified with multi-walled carbon nanotubes (MWCNTs) was used to detect amoxicillin in pharmaceutical formulations.This technique provides exceptional sensitivity, selectivity, and a low detection limit for the quantification of amoxicillin in pharmaceutical formulations.[60]
2.Electrochemical Quantification of Antiviral Drugs
(Acyclovir Detection in Pharmaceutical Tablets)
A voltammetric method using a boron-doped diamond electrode was developed to detect and quantify acyclovir, an antiviral drug.This method offers high sensitivity, selectivity, and a low recognition parameter for the quantification of amoxicillin in pharmaceutical drugs.
3.Electrochemical Analysis of Anticancer Drugs
(Cisplatin Detection using DNA-modified Electrodes)
A DNA-modified electrode was used to detect the interaction of cisplatin, a chemotherapy drug, with DNA. The change in electrochemical signal was used to study the drug’s binding to DNA.This method helps understand drug-DNA interactions, crucial for assessing the efficacy and side effects of anticancer drugs.
4.Electrochemical Biosensor for Monitoring Drug Metabolites
(Paracetamol (Acetaminophen) Metabolite Detection)
An electrochemical biosensor based on graphene-modified electrodes was developed to detect paracetamol and its metabolites in biological fluids.The sensor was used for real-time monitoring of drug metabolism in patients.[93]
5.Electrochemical Detection of Psychoactive Drugs (Cocaine Detection using a Disposable Electrochemical Sensor)A disposable screen-printed electrode modified with gold nanoparticles was used for the rapid and sensitive detection of cocaine in biological samples.This method is used in forensic analysis and roadside testing to detect cocaine use.
6.Electrochemical Analysis of Cardiovascular Drugs (Atenolol Detection using a Modified Carbon Electrode)Differential pulse voltammetry (DPV) with a carbon electrode modified with carbon black was applied to detect atenolol in pharmaceutical formulations.It allowed the quantification of atenolol, a common beta-blocker, with high sensitivity and specificity.
7.Electrochemical Detection of Anti-Inflammatory Drugs (Ibuprofen Detection in Pharmaceutical Products)Square wave voltammetry (SWV) with a modified gold electrode was used to detect ibuprofen in drug formulations.This technique provided a quick and delicate method for analyzing the content of ibuprofen in commercial drug products.[94]
8.Electrochemical Sensing of Antidepressant Drugs (Sertraline Detection using a Graphene-Modified Electrode)A graphene-modified electrode was developed to detect sertraline, an antidepressant drug, in pharmaceutical formulations using differential pulse voltammetry (DPV).The method was applied to quantify sertraline in commercial tablets.
9.Electrochemical Detection of Antimalarial Drugs (Chloroquine and Hydroxychloroquine Detection)An electrochemical method using a glassy carbon electrode was developed to detect chloroquine and hydroxychloroquine in pharmaceutical preparations.This method was useful during the COVID-19 pandemic when these drugs were tested for their potential antiviral activity.
10.Electrochemical Sensors for Antibiotic Residue Detection in Food
(Electrochemical Detection of Tetracycline Residue in Milk)
A sensor using a carbon-based electrode was developed to detect tetracycline residues in milk samples.This method provided a quick, sensitive, and cost-effective way to ensure food safety and compliance with drug residue regulations.
Table 3. Comparison of Electroanalytical Methods for Paracetamol Detection.
Table 3. Comparison of Electroanalytical Methods for Paracetamol Detection.
S. No.MethodDetection LimitSensitivitySelectivityAdvantagesDisadvantagesRef.
1.Cyclic Voltammetry (CV)ModerateModerateModerateProvides information on redox processes and reaction mechanismsLess sensitive compared to pulse techniques[97]
2.Differential Pulse Voltammetry (DPV)LowHighHighEnhanced sensitivity and resolution; suitable for trace analysisRequires more complex instrumentation
3.Square Wave Voltammetry (SWV)LowHighHighRapid analysis with high sensitivity; effective for noisy environmentsIt may require extensive optimization[98]
4.Amperometric DetectionVery LowVery HighModerateSuitable for continuous monitoring; simple instrumentationPotential interference from other electroactive species
5.Electrochemical Impedance Spectroscopy (EIS)VariableVariableHighProvides information on interfacial properties; useful for sensor developmentComplex data analysis; not typically used for direct quantification[99]
Table 4. Comparison between Electroanalysis and Spectrophotometry.
Table 4. Comparison between Electroanalysis and Spectrophotometry.
S. No.VariableElectroanalysisSpectrophotometryChromatographyMass SpectrometryFluorescence SpectroscopyRef.
1.AdvantageHigh sensitivity, ability to detect low concentrations, simple sample preparation, real-time monitoring, and low cost.Simple and quick analysis, good for quantifying compounds that absorb light at specific wavelengths, high throughput.Excellent separation of complex mixtures, high sensitivity, and specificity.Provides structural information, extremely high sensitivity and specificity, capable of analyzing complex mixtures.Direct analysis, low cost, minimal sample preparation.[100]
2.LimitationSelectivity can be influenced by interfering substances, requires electrode maintenanceLimited sensitivity for compounds that do not absorb light strongly, interference from other absorbing species, requires clear solutions.Time-consuming, requires expensive instrumentation and consumables, extensive sample preparation.Very expensive, requires skilled operation and maintenance, complex sample preparation.High sensitivity, capable of detecting very low concentrations, useful for biological samples.[101]
3.Comparative studyUsing DPV, detection at very low concentrations with high sensitivity and minimal interference.For paracetamol UV-Vis spectrophotometry required a derivatization step to improve sensitivity and faced interference from other absorbing substances in the sample.Analysis of ciprofloxacin HPLC offered high separation efficiency and sensitivity, but the analysis time was longer and required more extensive sample preparation.LC-MS offered detailed structural information and extremely high sensitivity, ideal for comprehensive metabolic profiling but at a higher cost and complexityProvided high sensitivity and specificity, but required derivatization of propranolol with a fluorescent marker, adding to the complexity and cost.[102]
Table 6. Several challenges and limitations of electroanalysis techniques [102,108].
Table 6. Several challenges and limitations of electroanalysis techniques [102,108].
S. No.ChallengesDescriptionImpactReasoningRef.
1.Electrode FoulingOver time, electrodes can become coated with reaction products or contaminants, reducing their effectiveness.Leads to decreased sensitivity, reproducibility, and accuracy.Regular cleaning or use of disposable electrodes.[116]
2.Interference from Other SpeciesOther electroactive species in the sample can interfere with the analyte signal.Causes overlapping signals and inaccurate measurements.Use of selective electrodes, chemical modification of electrodes, or sample pretreatment.
3.Complex Sample MatricesBiological, environmental, and industrial samples often contain complex mixtures.Difficult to isolate and measure specific analytes without interference.Advanced separation techniques (e.g., chromatography), selective electrodes, or signal processing methods.
4.Reproducibility and StabilityVariability in electrode preparation and environmental conditions can affect results.Difficult to achieve consistent and reliable measurements.Standardization of electrode preparation procedures and use of stable reference electrodes.[117]
5.Detection LimitsLimited by noise and background currents, particularly for low-concentration analytes.Difficult to detect trace levels of substances.Enhancement techniques such as pre-concentration, use of nanostructured materials, or signal amplification.
6.Kinetic and Mass Transport LimitationsReaction kinetics and mass transport to the electrode surface can limit the rate of electrochemical reactions.Affects the speed and efficiency of the analysis.Optimizing electrode design and experimental conditions to enhance mass transport.
7.SelectivityDifficulty in achieving high selectivity for a particular analyte in the presence of similar species.Inaccurate quantification and identification.Use of selective binding agents (e.g., enzymes, antibodies) or electrode modification.[118]
8.Instrumentation and CostAdvanced electroanalytical techniques require sophisticated and often expensive equipment.Limits accessibility for routine analysis or in resource-limited settings.Development of low-cost, portable devices.[119]
9.Environmental FactorsTemperature, pH, and ionic strength can affect electrochemical measurements.Variability in results and reduced reproducibility.Control of environmental conditions or use of robust sensor designs.
10.Surface CharacterizationDifficulty in characterizing and controlling the surface properties of electrodes.Affects reproducibility and sensitivity.Advanced surface characterization techniques (e.g., microscopy, spectroscopy) and consistent electrode preparation.[120]
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Kumar, R.; Salwan, S.; Kumar, P.; Bansal, N.; Kumar, B. Electroanalysis Advances in Pharmaceutical Sciences: Applications and Challenges Ahead. Analytica 2025, 6, 12. https://doi.org/10.3390/analytica6020012

AMA Style

Kumar R, Salwan S, Kumar P, Bansal N, Kumar B. Electroanalysis Advances in Pharmaceutical Sciences: Applications and Challenges Ahead. Analytica. 2025; 6(2):12. https://doi.org/10.3390/analytica6020012

Chicago/Turabian Style

Kumar, Ram, Sushant Salwan, Pawan Kumar, Nisha Bansal, and Bhupinder Kumar. 2025. "Electroanalysis Advances in Pharmaceutical Sciences: Applications and Challenges Ahead" Analytica 6, no. 2: 12. https://doi.org/10.3390/analytica6020012

APA Style

Kumar, R., Salwan, S., Kumar, P., Bansal, N., & Kumar, B. (2025). Electroanalysis Advances in Pharmaceutical Sciences: Applications and Challenges Ahead. Analytica, 6(2), 12. https://doi.org/10.3390/analytica6020012

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