Fake Pharmaceuticals: A Review of Current Analytical Approaches

Abstract

Recent incidents in India and abroad have drawn attention to the alarming rise of counterfeit and substandard pharmaceuticals. Cases such as the tragic deaths of several children in Madhya Pradesh due to contaminated cough syrup “Coldrif,” and reports of fake antibiotics and painkillers adulterated with chalk powder in Rajasthan, underline the severity of this issue. Poor-quality pharmaceuticals not only lead to treatment failure but also contribute to antimicrobial resistance and life-threatening adverse drug reactions.

These incidents erode public trust in healthcare systems and escalate economic burdens. Analytical chemistry now plays a crucial role in differentiating authentic from falsified drugs. Modern approaches, including chromatography, colorimetry, infrared and Raman spectroscopy, and mass spectrometry, have proven particularly effective. This review discusses the range of analytical tools developed in recent years to detect counterfeit medicines, examines their impact on human health and the global economy, and evaluates modern strategies for pharmaceutical verification and quality assurance.

Introduction

The global trade in counterfeit pharmaceuticals poses a serious challenge to public health, regulatory agencies, and the pharmaceutical industry. Fake pharmaceuticals encompass a wide range of illegal and substandard products, including medicines with false labeling of identity or origin, products containing incorrect or no active pharmaceutical ingredients (APIs), and legitimate drugs that have degraded due to poor storage or handling. The World Health Organization (WHO) has described this problem as a major public health threat that undermines decades of progress in medical treatment. The issue extends beyond regulatory noncompliance—it represents a deep ethical, social, and humanitarian concern. Counterfeiters exploit economic inequalities, supply chain weaknesses, and digital marketplaces to circulate falsified drugs globally.

It is estimated that approximately 10% of all medicines distributed worldwide are falsified or substandard, with an even higher prevalence in low- and middle-income countries. Nearly half of these reach consumers through unregulated online pharmacies and black- market networks. The problem is no longer restricted to developing regions; developed nations also experience growing incidences of lifestyle drug counterfeiting, particularly in the domains of hormones, erectile dysfunction drugs, and psychoactive medications. Most counterfeit production originates from manufacturing hubs in East and Southeast Asia, facilitated by complex transnational trade and limited oversight of supply chains. These fake products endanger lives, damage brand reputations, and impose significant economic burdens on healthcare systems.

Unlike genuine pharmaceuticals, falsified drugs are inconsistent in quality, safety, and efficacy. Even if they contain some level of active ingredient, they often fail to comply with Good Manufacturing Practice (GMP) standards. Moreover, the environmental consequences of improper disposal and pharmaceutical residues further complicate the issue. Addressing this multifaceted problem demands global cooperation, technological innovation, and widespread access to reliable analytical testing methods capable of identifying counterfeit substances rapidly and accurately.

Impact of Fake Pharmaceuticals on Public Health and Economy

The public health impact of counterfeit pharmaceuticals is profound and far-reaching. Substandard and falsified medicines undermine the effectiveness of healthcare delivery by producing unpredictable therapeutic outcomes. When patients consume drugs that lack proper APIs or contain incorrect dosages, diseases remain untreated or worsen over time. This not only delays recovery but also fosters antimicrobial resistance (AMR), a global threat that jeopardizes the efficacy of even legitimate medications. The World Health Organization estimates that counterfeit medicines cause over one million deaths annually, primarily in Africa and Southeast Asia, where regulatory oversight is weak and access to quality-assured drugs is limited.

Beyond immediate health risks, fake pharmaceuticals lead to economic instability. Patients and healthcare systems waste substantial resources on ineffective or harmful treatments. Hospitals face increased admissions due to treatment failures, while national governments must allocate additional budgets for drug monitoring and regulation. The pharmaceutical industry, a cornerstone of biomedical innovation, suffers revenue losses estimated at tens of billions of dollars annually. Moreover, consumer confidence in both local and international brands diminishes, reducing public trust in healthcare institutions. Such erosion of trust can have cascading consequences, including vaccine hesitancy and avoidance of legitimate medical interventions.

Socially, the presence of counterfeit drugs exacerbates inequality. Vulnerable populations in low-income regions—where counterfeiters exploit economic desperation—bear the greatest burden. These individuals often lack the means to verify the authenticity of drugs or to purchase from reliable sources. On a global scale, counterfeit pharmaceuticals weaken international trade relations and threaten sustainable development goals (SDGs) associated with good health and economic growth. Addressing this issue thus requires not only technological innovation but also educational campaigns, international collaboration, and policy reform.

Analytical Methods Used in Detection of Counterfeit Drugs

Analytical science provides the foundation for detecting counterfeit pharmaceuticals. Methods used for authentication rely on chemical, physical, and spectroscopic principles that differentiate genuine products from falsified ones. These methods vary in complexity— from rapid field tests like colorimetry to advanced techniques such as mass spectrometry and nuclear magnetic resonance (NMR). The following subsections discuss key analytical approaches that have proven effective in combating pharmaceutical fraud.

Capillary Electrophoresis (CE)

Capillary electrophoresis (CE) separates charged molecules based on their mobility in an electric field within a capillary tube. It is known for its precision, rapid analysis, and minimal reagent consumption. CE has been applied to detect adulterants in herbal formulations and weight-control supplements by separating compounds such as ephedrine, caffeine, and furosemide within minutes. The method’s reproducibility and ability to analyze complex mixtures make it invaluable in forensic pharmaceutical studies. Furthermore, CE can be easily coupled with ultraviolet or mass spectrometric detection to enhance sensitivity and reliability.

Colorimetry

Colorimetry relies on the quantitative measurement of color intensity to determine the presence or concentration of a substance. Paper-based colorimetric assays have been developed as portable and inexpensive diagnostic tools, especially in regions lacking laboratory infrastructure. One notable example is the field test for counterfeit artesunate tablets, which produces visible color changes when the drug reacts with specific reagents. The results can be interpreted visually or through smartphone-based image analysis applications. Such techniques democratize drug testing, empowering pharmacists and health workers to identify falsified products quickly.

High-Performance Liquid Chromatography (HPLC)

High-performance liquid chromatography (HPLC) is a cornerstone technique in pharmaceutical analysis. It separates compounds based on their interactions with stationary and mobile phases under high pressure. When combined with electrospray ionization tandem mass spectrometry (HPLC-ESI-MS/MS), the technique achieves exceptional accuracy in detecting synthetic adulterants. HPLC is widely used to verify the composition of herbal remedies and dietary supplements that may contain undeclared drugs such as steroids or amphetamine derivatives. Its strengths include high precision, reproducibility, and adaptability to varied compound types, though it requires skilled operators and costly instrumentation.

High-Performance Thin-Layer Chromatography (HPTLC)

HPTLC combines the simplicity of traditional TLC with automated precision. It uses fine- particle adsorbents and digital image evaluation to produce high-resolution fingerprints of complex mixtures. This method is especially useful for authenticating traditional herbal formulations and assessing batch consistency. HPTLC’s environmental advantages—low solvent use and minimal waste—make it sustainable and cost-efficient. Additionally, recent advancements have enabled coupling with densitometric and fluorescence detection systems, increasing its diagnostic potential.

Infrared and Near-Infrared Spectroscopy (IR/NIR)

Infrared spectroscopy (IR) and near-infrared spectroscopy (NIR) are rapid, non-destructive techniques that identify materials by measuring their molecular vibrations. Fourier- transform infrared (FT-IR) imaging and desorption electrospray ionization (DESI) mass spectrometry have been successfully employed to assess the chemical composition and homogeneity of counterfeit drugs. These techniques require minimal sample preparation and can be applied directly to solid tablets. Their ability to generate chemical fingerprints within seconds makes them ideal for field-based and border control applications.

Mass Spectrometry (MS)

Mass spectrometry (MS) determines molecular masses by analyzing ionized particles according to their mass-to-charge ratios. When combined with chromatography, it offers unparalleled sensitivity in identifying trace components, degradation products, and impurities. MS has become indispensable in drug discovery, forensic science, and regulatory testing. For counterfeit detection, direct analysis in real time (DART) MS enables rapid screening of solid samples without extensive preparation, allowing immediate verification of pharmaceutical authenticity.

Nuclear Magnetic Resonance (NMR) Spectroscopy

Nuclear magnetic resonance (NMR) spectroscopy provides molecular-level insight by detecting magnetic properties of atomic nuclei. It is considered one of the most definitive methods for structural elucidation. In the context of counterfeit drug analysis, NMR distinguishes genuine products by comparing their unique spectral signatures with reference data. Recent miniaturized NMR instruments have made the technology more accessible, facilitating on-site drug authentication in research and quality control laboratories.

Raman Spectroscopy

Raman spectroscopy, based on inelastic scattering of monochromatic light, identifies molecular structures and polymorphic forms in solid-state samples. It is highly effective in analyzing coated tablets, detecting contaminants, and confirming API presence. The non- invasive nature of Raman spectroscopy allows sealed package analysis, eliminating the need for sample destruction. For instance, Raman studies of counterfeit Levitra revealed substitution of vardenafil with sildenafil, demonstrating its value for forensic applications.

Thin-Layer Chromatography (TLC)

Thin-layer chromatography (TLC) remains a reliable and affordable analytical technique, particularly in developing regions. It separates components of a mixture on a flat adsorbent surface using a suitable solvent system. TLC has been applied to assess the quality of antimalarial and antibiotic drugs, revealing that up to one-third of tested samples in African markets were substandard. Although less precise than HPLC, TLC’s simplicity and accessibility make it a vital first-line tool for pharmaceutical screening.

Conclusion

The proliferation of counterfeit pharmaceuticals presents an ongoing global health emergency. The consequences—therapeutic failure, toxicity, and economic loss—demand urgent, coordinated responses. Analytical chemistry provides powerful means to counter this threat through precise, reproducible, and scalable detection technologies. Future progress lies in integrating advanced spectroscopic and chromatographic tools with artificial intelligence and blockchain-enabled supply chain monitoring. International collaboration, coupled with stronger legal frameworks and public education, is essential to safeguard medicine authenticity and restore public confidence in healthcare systems.

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