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Background: Selective androgen receptor modulators (SARMs) are small synthetic drug molecules that are still not approved as medicine in Europe or the United States but are sold on illegal websites to improve sport performance, particularly bodybuilding. Aim: To address the quality issues of illegal SARM products and their increasing diffusion in Italy with their potential health risks for consumers. Methods: Web-based tools were used to investigate retail websites, trending searches, and information exchange via social media. Thirteen SARM products, purchased on retail websites accessible from Italy, were subject to visual inspection and chemical analysis by mass spectrometry and quantitative nuclear magnetic resonance. Outcomes: The primary outcome was demonstration of additional health risks due to the illicit presence of other active ingredients, contamination, and misdosage in SARM products sold on the internet. The secondary outcome was to show the increasing trend of interest in Italy for these products. Results: Most websites reported misleading information; specifically, the statement "for research only" was reported notwithstanding indications on dosage and training phases. The trending search showed that interest toward SARMs increased in Italy in the last years. The use of these products is clearly encouraged by the emerging phenomenon of "broscience" as revealed in socials. Visual inspection evidenced nonconform labeling. Qualitative analysis confirmed the presence of the stated SARM in about 70% of samples. In 23% of samples, the expected SARM was not detected but a different one instead, and in 1 sample, no SARMs were detected. Other undeclared pharmaceutical substances (tamoxifen, clomifene, testosterone, epimethandienone, tadalafil) were measured in 30% of samples. The copresence of >1 active substance was observed in >60% of samples. Quantitative nuclear magnetic resonance data showed nonuniform content ranging from 30% to 90% of the label claim. Clinical Implications: The use of SARMs, in the presence of unexpected life-threatening reactions in persons using the products to increase sport performance, should be assessed. Strengths and Limitations: This investigation involved an integrated approach to study SARM products and related sociologic aspects. The main shortcomings are the limited number of samples and retail websites in the clear web investigated. Conclusion: SARMs sold online as food supplement-like products represent a health hazard due to the presence of unapproved and undeclared active substances. The presence of contaminants clearly indicates the absence of good manufacturing practices in the production, which increases the health risks.
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A new method for rapid determination of the content of selective androgenic receptor modulators (SARMs) andarine, cardarine, ligandrol, ostarine and S-23 in capsules by 1H- and 19F-high resolution nuclear magnetic resonance spectroscopy was described and validated. Specificity, linearity, accuracy, precision, detection and quantification limits were considered as validation parameters. Full 1H-, 13C- and 19F-NMR structural assignment of the SARMs is provided as a tool for self-standing identification without a reference standard. Amounts of 7-15 mg of SARMs/capsule were detected in different products with an intermediate precision of 0.8-1.7% in 4 to 20 minutes of analysis time. The validation results and rapidity of analysis confirm the applicability of the method for large-scale screening. The statistical analysis of the results from 19F- and 1H-quantitative NMR showed that both approaches were equally effective, thus expanding the potential use of the methodology to non-fluorinated SARMs. At present, no SARM has been approved for human consumption; however, SARMs are actually used by bodybuilders and recreational athletes, who purchase them even though the risk-benefit ratio of these molecules has not been definitively established.
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Anabolizantes , Receptores Androgénicos , Humanos , Andrógenos/química , Antagonistas de Andrógenos , Espectroscopía de Resonancia Magnética , Anabolizantes/químicaRESUMEN
INTRODUCTION: A case study is reported on anti-motion sickness transdermal patches sold in the Internet, claiming to contain only natural ingredients but, actually, containing undeclared medicinal active substances. The visual inspection of the samples evidenced many inconsistencies in secondary and primary packaging, missing of various legal information and a non-compliant "CE" mark. METHODS: The qualitative analysis was performed by liquid chromatography - high resolution mass spectrometry and the quantitative by liquid chromatography with diode array detector. RESULTS: The analyses evidenced the presence of the antihistaminic drug Diphenhydramine and of other active substances (Capsaicin, a transdermal absorption enhancer, and Diclofenac in traces, probably a contaminant from other productions of the same plant). Moreover, the presence of several trace elements, including those potentially toxic to humans, was assessed by ICP-MS analysis. CONCLUSIONS: The case discussed is a new case of "medicines in disguise" never reported in literature, and shows the presence of tangible risks for public health.
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Preparaciones Farmacéuticas , HumanosRESUMEN
Falsification of drugs, entailing the use of drug substances from unknown unapproved suppliers, is one of the main concerns for the quality of medicines. Therefore, traceability of active ingredients represents an effective tool to fight the illegal trade of medicinal products. In this view, the present pilot study explores the profile of carvedilol active ingredients and possible differences related to the origin. Sixteen samples were examined by near-infrared spectroscopy (NIR), proton nuclear magnetic resonance (1H-NMR spectrometry) and liquid chromatography mass spectrometry (LC-MS) Q-TOF and the data were analysed by principal component analysis (PCA), cluster analysis and PLSDA discriminant analysis. The results evidenced that the combined information from the three techniques gave good classification of the samples neatly distinguishing the APIs from European countries from the APIs manufactured out of Europe. In particular, NIR spectroscopy provided effective separation between European and non-European manufacturers and 1H-NMR or LC-MS added specific information related to the separation. Concerning LC-MS Q-TOF, the analysis of multiple isobaric peaks proved to be highly predictive of the drug substance origin and emerged as a promising tool in the field of medicine traceability.
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Quimiometría , Espectrometría de Masas en Tándem , Carvedilol , Cromatografía Liquida , Espectroscopía de Resonancia Magnética/métodos , Preparaciones Farmacéuticas , Proyectos Piloto , Espectroscopía de Protones por Resonancia MagnéticaRESUMEN
This paper describes a case of medicine in disguise: seized tattoo inks containing lidocaine and tetracaine at high concentration. Identification of anaesthetics was performed by LC MS Q-TOF with ESI+ source, by accurate mass measurement and by comparing the fragmentation patterns of molecular ions, at 30â¯V and 10â¯V of collision-offset voltage, with reference standards. Quantification was also performed by LC MS Q-TOF on the chromatographic peaks in the extracted ion chromatograms, by calibration curves obtained at different standard concentrations and by standard additions approach. The measurement uncertainty was estimated from validation data. The paper gives also chromatographic parameters, MS and MS/MS data and a quantitation method, with a full validation, of other six "caines". Thus the paper intends to provide a tool for identification and quantitation of the most common local anaesthetics that could be fraudulently added to tattoo inks. The results here reported show that the seized samples of inks represent a serious health risk owing to the high anaesthetic content - therapeutic-like dosage - found.
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Anestésicos/análisis , Tinta , Lidocaína/análisis , Tatuaje , Tetracaína/análisis , Cromatografía Liquida , Humanos , Espectrometría de MasasRESUMEN
Adverse reactions have been reported for antibiotics produced via fermentation with fish peptone due to Histamine contamination. Just few micrograms of Histamine can result in adverse reactions when administered intravenously. Thus in this paper a new method for identification and quantitation of Histamine at ppm levels in the antibiotic Gentamicin is described. The method is based on separation of Histamine from Gentamicin and other excipients present in the drug matrix, by hydrophilic interaction liquid chromatography (HILIC) coupled to a Q-TOF/MS detector; quantitation is based on the standard addition approach. The method was validated for repeatability, inter-day precision, specificity, accuracy (relative and absolute bias) linearity, limit of detection and quantitation. Uncertainty was estimated and evaluated by comparison with values expected according to the Horwitz theory. The method showed satisfactory performances and good sensitivity, reaching a limit of quantitation of approximately 1 ppm. The method proposed can be a starting point for the development of Histamine quantitation methods in other antibiotics or even in other medicinal products which active ingredient is produced via fermentation in presence of fish peptone.
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Antibacterianos/análisis , Cromatografía Liquida , Contaminación de Medicamentos , Gentamicinas/análisis , Histamina/análisis , Espectrometría de Masas en Tándem , Calibración , Cromatografía Liquida/normas , Histamina/efectos adversos , Estándares de Referencia , Reproducibilidad de los Resultados , Espectrometría de Masas en Tándem/normas , IncertidumbreRESUMEN
A nontargeted approach based on liquid chromatography equipped with a quadrupole time-of-flight mass detector (LC-MS Q-TOF) joined to nuclear magnetic resonance (NMR) analysis allowed rapid identification and quantification of the anti-inflammatory drug aceclofenac in illegal Adderall tablets. The largest chromatographic peak had m/z = 354.030 and m/z = 376.012 matching, respectively, the ionic structures (M + H)+ and (M + Na)+ of a molecule M. The accurate mass data generated the molecular formula C16 H13 Cl2 NO4 . A screening of the pharmaceutical active substances having that molecular formula together with the MS/MS fragmentation pattern suggested aceclofenac. Aceclofenac structure was unambiguously confirmed by 1 H and 13 C NMR experiments. The aceclofenac content was 90 mg/tablet (RSD 2%) as detected by quantitative NMR. Information on the identity and content of illegal drugs is required for legal purposes; it supports in evaluating the effective impact on users safety, and it is useful for control laboratories using a targeted approach in their analytical activities.
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OBJECTIVES: The increasing illegal and on-line market of medicines and food supplements is helping the widespread diffusion of harmful counterfeit and forbidden products among consumers of developed countries. The objectives of this survey were the description of the main frauds recognized by public officers and the detection of illegal or counterfeit drugs and food supplements. METHODS: Medicines and food supplements found by Police forces on the illegal market or resulting from seizures made by Italian Customs authorities were visually inspected and analysed to evaluate their quality and the presence of other undeclared substances. RESULTS: The visual inspection and the chemical analysis revealed unsuitable packaging (mostly lacking of adequate information for consumers), absence of the declared active substances and presence of undeclared active substances. Products containing doping agents, illegal substances and active ingredients requiring medical supervision were found. CONCLUSION: The present work confirmed the health risk associated with assumption of medicines purchased on the Internet and from the illegal supply chain and evidenced a new threat to consumer safety related to the presence of pharmaceutical active ingredients in food supplements claiming to contain only "natural ingredients".
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Medicamentos Falsificados , Suplementos Dietéticos , Tráfico de Drogas , Drogas Ilícitas/efectos adversos , Internet , Seguridad de Productos para el Consumidor , Etiquetado de Medicamentos , Humanos , Italia , Preparaciones Farmacéuticas/análisis , Medición de Riesgo , Encuestas y CuestionariosRESUMEN
Many proteins belonging to the amyloid family share the tendency to misfold and aggregate following common steps, and display similar neurotoxicity. In the aggregation pathway different kinds of species are formed, including several types of oligomers and eventually mature fibers. It is now suggested that the pathogenic aggregates are not the mature fibrils, but the intermediate, soluble oligomers. Many kinds of aggregates have been described to exist in a metastable state and in equilibrium with monomers. Up to now it is not clear whether a specific structure is at the basis of the neurotoxicity. Here we characterized, starting from the early aggregation stages, the oligomer populations formed by an amyloid protein, salmon calcitonin (sCT), chosen due to its very slow aggregation rate. To prepare different oligomer populations and characterize them by means of photoinduced cross-linking SDS-PAGE, Energy Filtered-Transmission Electron Microscopy (EF-TEM) and Circular Dichroism (CD) spectroscopy, we used Size Exclusion Chromatography (SEC), a technique that does not influence the aggregation process leaving the protein in the native state. Taking advantage of sCT low aggregation rate, we characterized the neurotoxic potential of the SEC-separated, non-crosslinked fractions in cultured primary hippocampal neurons, analyzing intracellular Ca(2+) influx and apoptotic trend. We provide evidence that native, globular, metastable, prefibrillar oligomers (dimers, trimers and tetramers) were the toxic species and that low concentrations of these aggregates in the population was sufficient to render the sample neurotoxic. Monomers and other kind of aggregates, such as annular or linear protofibers and mature fibers, were totally biologically inactive.
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Amiloide/química , Amiloide/toxicidad , Encéfalo/patología , Hipocampo/patología , Animales , Encéfalo/efectos de los fármacos , Calcio/metabolismo , Células Cultivadas , Cromatografía en Gel , Dicroismo Circular , Reactivos de Enlaces Cruzados/farmacología , Dimerización , Electrofisiología , Hipocampo/efectos de los fármacos , Microscopía Electrónica de Transmisión , Fotoquímica , Ratas , Espectrometría de Masa por Láser de Matriz Asistida de Ionización DesorciónRESUMEN
Novel synthetic analogs of Sildenafil are constantly detected as adulterants in counterfeit drugs and dietary supplements. Their intake constitutes a serious health hazard as side effects are unknown. In this paper an investigation is carried out on NMR and MS/MS spectra of Sildenafil, Thiosildenafil, Acetildenafil and thirteen of their analogs: a list of key signals is reported and discussed with the intent to provide a tool that can help in detecting adulteration and in elucidating the structure of novel analogs. In this view extensive spectral data were reported, discussed and summarized in tables. A discussion on mass fragmentation and NMR chemical shifts is also provided to rationalize assignation. Moreover, a comprehensive information on the route of synthesis is provided for the benefit of those medicines control laboratories that need to synthesize analogs reference standards in-house.
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Espectroscopía de Resonancia Magnética/métodos , Piperazinas/análisis , Pirimidinas/análisis , Sulfonas/análisis , Espectrometría de Masas en Tándem/métodos , Medicamentos Falsificados/análisis , Suplementos Dietéticos/análisis , Contaminación de Medicamentos , Inhibidores de Fosfodiesterasa 5/análisis , Inhibidores de Fosfodiesterasa 5/química , Piperazinas/química , Purinas/análisis , Purinas/química , Pirimidinas/química , Citrato de Sildenafil , Sulfonas/químicaRESUMEN
INTRODUCTION: In developed countries the phenomenon of pharmaceutical counterfeiting is steadily increasing through the illegal and the Internet market. Medicines for the treatment of erectile dysfunctions containing phosphodiesterase type 5 inhibitors (PDE5) are especially prone to falsification. AIMS: To obtain evidence of the health risks for patients taking these products and to provide useful information to general practitioners and specialists in sexual medicine. METHODS: First the samples were visually inspected and then analyzed to get information about their identity and quality. MAIN OUTCOME MEASURES: A survey on the PDE5 medicines analyzed by the Italian official medicines control laboratory between 2005 and 2011 was performed. All the analyzed medicines were gathered from the Italian illegal market (seizures by police forces) or were bought from illegal online pharmacies. Results. The study revealed that 24% of the analyzed samples were counterfeit and 54% were illegal medicines. In 12% of the cases an intermediate classification (illegal/counterfeit) was assigned. Only 7% of the samples were original. Moreover, the examination of the packaging evidenced potential risks: outer and immediate packaging missing; inconsistency between the carton box and the blister as regards the expiry date and/or the batch number; expiry date or manufacturer's name or country missing. CONCLUSIONS: In 19% of the samples a potential health risk for patients was identified due to either the presence in the sample of more than one undeclared PDE5(s) or an amount of the active ingredient higher than that declared (up to 190% of the maximum dose) or to the presence of potentially dangerous excipients of non-pharmaceutical origin or quality (e.g., gypsum or non-purified talc).
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Medicamentos Falsificados/administración & dosificación , Medicamentos Falsificados/efectos adversos , Disfunción Eréctil/tratamiento farmacológico , Fraude , Humanos , Internet , Italia , Masculino , Persona de Mediana Edad , Inhibidores de Fosfodiesterasa 5RESUMEN
Amyloid proteins of different aminoacidic composition share the tendency to misfold and aggregate in a similar way, following common aggregation steps. The process includes the formation of dimers, trimers, and low molecular weight prefibrillar oligomers, characterized by the typical morphology of globules less than 10 nm diameter. The globules spontaneously form linear or annular structures and, eventually, mature fibers. The rate of this process depends on characteristics intrinsic to the different proteins and to environmental conditions (i.e., pH, ionic strength, solvent composition, temperature). In the case of neurodegenerative diseases, it is now generally agreed that the pathogenic aggregates are not the mature fibrils, but the intermediate, soluble oligomers. However, the molecular mechanism by which these oligomers trigger neuronal damage is still unclear. In particular, it is not clear if there is a peculiar structure at the basis of the neurotoxic effect and how this structure interacts with neurons. This review will focus on the results we obtained using salmon Calcitonin, an amyloid protein characterized by a very slow aggregation rate, which allowed us to closely monitor the aggregation process. We used it as a tool to investigate the characteristics of amyloid oligomers formation and their interactions with neuronal cells. Our results indicate that small globules of about 6 nm could be the responsible for the neurotoxic effects. Moreover, our data suggest that the rich content in lipid rafts of neuronal cell plasma membrane may render neurons particularly vulnerable to the amyloid protein toxic effect.
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Amiloide/metabolismo , Calcitonina/metabolismo , Proteínas de Peces/metabolismo , Agregación Patológica de Proteínas/metabolismo , Salmón/metabolismo , Animales , Microdominios de Membrana/metabolismo , Microdominios de Membrana/ultraestructura , Neuronas/metabolismo , Neuronas/ultraestructuraRESUMEN
The growth of pharmaceutical counterfeiting is a major public health problem. This growth is resulting in a proportional increase in the number of samples that medicines control laboratories have to test. Thus the need for simple and affordable preliminary screening methods to be used by inspectors to decide in the field whether to collect a sample for further laboratory analysis or not. This paper intends to evaluate the possibility to employ for preliminary examinations of suspicious samples an optical spectrophotometer (colorimeter) used in the graphic industry, capable of measuring the reflectance visible spectrum of solid materials. The colorimeter was tested on original and counterfeited Viagra, Cialis and Levitra by measuring the colour of tablets' surface and of a specific spot of the packages. Various batches of the original drugs were employed both to investigate precision and robustness of the technique and to build spectral libraries. These libraries were used to compare suspicious samples to the corresponding original by means of a wavelength distance pattern recognition method. The method was eventually tested on suspicious samples sized by police authorities in order to evaluate its effectiveness. The device resulted precise and robust toward ambient conditions changes, although some limits emerged: the libraries of original samples need a frequent update and a lower precision is to be expected for tablets which surface is extremely convex.
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Colorimetría/instrumentación , Fraude/prevención & control , Reconocimiento de Normas Patrones Automatizadas/métodos , Comprimidos/análisis , Colorimetría/métodos , Embalaje de Medicamentos , Propiedades de SuperficieRESUMEN
A specific neuronal vulnerability to amyloid protein toxicity may account for brain susceptibility to protein misfolding diseases. To investigate this issue, we compared the effects induced by oligomers from salmon calcitonin (sCTOs), a neurotoxic amyloid protein, on cells of different histogenesis: mature and immature primary hippocampal neurons, primary astrocytes, MG63 osteoblasts and NIH-3T3 fibroblasts. In mature neurons, sCTOs increased apoptosis and induced neuritic and synaptic damages similar to those caused by amyloid beta oligomers. Immature neurons and the other cell types showed no cytotoxicity. sCTOs caused cytosolic Ca(2+) rise in mature, but not in immature neurons and the other cell types. Comparison of plasma membrane lipid composition showed that mature neurons had the highest content in lipid rafts, suggesting a key role for them in neuronal vulnerability to sCTOs. Consistently, depletion in gangliosides protected against sCTO toxicity. We hypothesize that the high content in lipid rafts makes mature neurons especially vulnerable to amyloid proteins, as compared to other cell types; this may help explain why the brain is a target organ for amyloid-related diseases.
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Amiloide/efectos adversos , Apoptosis/efectos de los fármacos , Hipocampo/metabolismo , Microdominios de Membrana/metabolismo , Neuritas/metabolismo , Amiloide/farmacología , Animales , Astrocitos/metabolismo , Astrocitos/patología , Hipocampo/patología , Microdominios de Membrana/patología , Ratones , Células 3T3 NIH , Neuritas/patología , Osteoblastos/metabolismo , Osteoblastos/patología , RatasRESUMEN
Diclofenac sodium is a nonsteroidal anti-inflammatory drug widely used in painful and inflammatory diseases. It can exist in different hydrate phases. Recently the physico-chemical and pharmaceutical properties of a trihydrate form, named DSH3 were reported by the same authors. This short communication discusses how samples of a same polymorphic form can display dissimilar analytical signatures when obtained by different routes. Data from hot-stage microscopy, FT-IR spectroscopy, X-ray powder diffraction (XRDP) and thermal analysis were used to characterise the DSH3 samples prepared by different methods. Through the case study of diclofenac sodium, this work highlights how the method used to prepare a specific crystal modification can generate samples with different morphologies and therefore different properties and physical stability.
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Diclofenaco/química , Cristalización , Espectroscopía Infrarroja por Transformada de Fourier , Difracción de Rayos XRESUMEN
BACKGROUND: The presence of counterfeits and sub-standards in African medicines market is a dramatic problem that causes many deaths each year. The increase of the phenomenon of pharmaceutical counterfeiting is due to the rise of the illegal market and to the impossibility to purchase branded high cost medicines. METHODS: In this paper the results of a quality control on antimalarial tablet samples purchased in the informal market in Congo, Burundi and Angola are reported. The quality control consisted in the assay of active substance by means of validated liquid chromatographic methods, uniformity of mass determination, disintegration and dissolution tests. Moreover, a general evaluation on label and packaging characteristics was performed. RESULTS: The results obtained on thirty antimalarial tablet samples containing chloroquine, quinine, mefloquine, sulphadoxine and pyrimethamine showed the presence of different kinds of problems: a general problem concerning the packaging (loose tablets, packaging without Producer name, Producer Country and sometimes without expiration date); low content of active substance (in one sample); different, non-declared, active substance (in one sample); sub-standard technological properties and very low dissolution profiles (in about 50% of samples). This last property could affect the bioavailability and bioequivalence in comparison with branded products and could be related to the use of different excipients in formulation or bad storage conditions. CONCLUSION: This paper evidences that the most common quality problem in the analysed samples appears to be the low dissolution profile. Here it is remarked that the presence of the right active substance in the right quantity is not a sufficient condition for a good quality drug. Dissolution test is not less important in a quality control and often evidences in vitro possible differences in therapeutic efficacy among drugs with the same active content. Dissolution profile can be dramatically affected by the choice of excipients in the oral solid formulation and, in many cases, is out of specifications due to the absence of formulation studies by producers of developing countries.
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Antimaláricos/provisión & distribución , Antimaláricos/normas , Angola , Antimaláricos/química , Burundi , Cromatografía , Congo , Etiquetado de Medicamentos/normas , Embalaje de Medicamentos/normas , Humanos , Control de Calidad , Solubilidad , Comprimidos/química , Comprimidos/normas , Comprimidos/provisión & distribuciónRESUMEN
Calcitonin is a polypeptidic hormone involved in calcium metabolism in the bone. It belongs to the amyloid protein family, which is characterized by the common propensity to aggregate acquiring a beta-sheet conformation and include proteins associated with important neurodegenerative diseases. Here we show for the first time, to our knowledge, by transmission electron microscopy (TEM) that salmon-calcitonin (sCT) forms annular oligomers similar to those observed for beta-amyloid and alpha-sinuclein (Alzheimer's and Parkinson's diseases). We also investigated the interaction between sCT and model membranes, such as liposomes, with particular attention to the effect induced by lipid "rafts" made of cholesterol and G(M1). We observed, by TEM immunogold labeling of sCT, that protein binding is favored by the presence of rafts. In addition, we found by TEM that sCT oligomers inserted in the membrane have the characteristic pore-like morphology of the amyloid proteins. Circular dichroism experiments revealed an increase in beta-content in sCT secondary structure when the protein was reconstituted in rafts mimicking liposomes. Finally, we showed, by spectrofluorimetry experiments, that the presence of sCT allowed Ca(2+) entry in rafts mimicking liposomes loaded with the Ca(2+)-specific fluorophore Fluo-4. This demonstrates that sCT oligomers have ion-channel activity. Our results are in good agreement with recent electrophysiological studies reporting that sCT forms Ca(2+)-permeable ion channels in planar model membranes. It has been proposed that, beyond the well-known interaction of the monomer with the specific receptor, the formation of Ca(2+) channels due to sCT oligomers could represent an extra source of Ca(2+) entry in osteoblasts. Structural and functional data reported here support this hypothesis.
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Calcitonina/química , Colesterol/química , Membrana Dobles de Lípidos/química , Microdominios de Membrana/química , Compuestos de Anilina , Calcio/química , Canales de Calcio/química , Dicroismo Circular , Colorantes Fluorescentes , Liposomas/química , Microscopía Electrónica de Transmisión , Porosidad , Estructura Secundaria de Proteína , XantenosRESUMEN
Pharmaceutical counterfeiting is more and more a public health problem, especially in developing countries where the most counterfeit drugs are antibiotics, antimalarials and other life-saving drugs. The evaluation of the phenomenon extent is of great concern to the World Health Organization for carrying out a global strategy to combat the phenomenon. To this purpose, a reversed-phase liquid chromatographic method to perform the separation and simultaneous determination of three different kinds of antimalarial drugs (chloroquine, quinine and mefloquine) was developed. The method was validated by using both commercial and in-laboratory produced tablets and was then verified on various in-laboratory produced formulations differing in excipient composition. Finally, the method was successfully applied to the analysis of medicinal samples purchased from the informal market in Congo, Burundi and Angola.