The discovery of the two unsymmetrically coupled dimeric naphthylisoquinoline alkaloids, the mbandakamines B3 and B4, showing a high steric hindrance at the central biaryl axis and displaying pronounced antiplasmodial activities, is described.
In the context of post-marketing surveillance supporting public-health authorities to take evidence-based decisions to fight the spread of poor-quality medicines, the quality of antimalarial artemether-lumefantrine (AL) medicines was assessed in the Democratic Republic of the Congo (DRC). A total of 150 samples of AL-containing products was collected from private pharmaceutical outlets in 8 main cities: Goma, Kikwit, Kinshasa, Kisangani, Lubumbashi, Matadi, Mbandaka, and Mbuji-Mayi. All drug samples were successively analyzed by visual inspection, thin-layer chromatography (TLC), and high-performance liquid chromatography (HPLC) following The International Pharmacopoeia. Of the 150 collected drug samples, 3 (2%) failed the visual inspection as they had shelf lives different from those of other samples with the same brand name. Four samples (2.7%) did not pass the TLC test as they contained only 1 or even none of the 2 declared active pharmaceutical ingredients (APIs). HPLC assays showed that 46 (30.7%) samples had artemether contents below 90% and 17 (11.3%) above 110% of the content claimed on the label. For lumefantrine, 32 (21.7%) samples had contents below 90%, and 8 (5.3%) had contents above 110%. This survey in DRC gives evidence that poor-quality antimalarial medicines are widely present. Based on 3 detection techniques, the study shows the necessity to equip developing countries with modern techniques such as HPLC, which, if combined with affordable techniques like TLC, could provide a pertinent analytical strategy to combat drug counterfeiting and poor manufacturing.
A simple and robust CZE method was developed for the separation and quantification of the antimalarial compound amodiaquine as well as three of its synthetic impurities at a concentration equal to or lower than 0.5%. For capillary electrophoresis, a fused-silica capillary, a background electrolyte of 100 mM sodium phosphate buffer at a pH value of 6.2, a voltage of +20 kV, and a detection wavelength of 220 nm were used, allowing the determination of the analytes within 20 min. The method was validated according to the guideline Q2(R1) of the International Council for Harmonization with respect to linearity, precision, accuracy, limit of detection and limit of quantification, and was successfully applied to evaluate the quality of drug samples collected in the Democratic Republic of the Congo. Quantitative analysis results obtained by the CZE method were compared to those obtained with the contemporary HPLC method described in The International Pharmacopoeia.
BackgroundEnvironmental pollutants are known to be ubiquitous and may present toxic effects (endocrine-disruption properties, carcinogenicity…). Therefore, they represent a real threat to human health. The aim of the present study was to assess the content of environmental pollutants (inorganic, persistent, and non-persistent pollutants) in biological samples (urine, serum, and whole blood), collected from volunteers in Kinshasa, capital of Democratic Republic of Congo, in order to estimate the exposure level in the population of Kinshasa to environmental pollutants.MethodsFrom randomly selected 15 volunteers living in Kinshasa, aged from 25 to 66 years, including 10 men and 5 women, urine, whole blood, and serum samples were used in this study to estimate the contents in these environmental pollutants, using Inductively Coupled Plasma Mass Spectrometry, Gas Chromatography coupled to Mass Spectrometry, and Liquid Chromatography coupled to Mass Spectrometry.ResultsWhen compared to data nationally and internationally available, the preliminary outcomes of this study indicated a high level of exposure to environmental pollutants in the population of Kinshasa, especially for arsenic, cadmium, lead, benzophenone-3, methyl-paraben, propyl-paraben, triclosan, mono-ethyl phthalate, mono-n-butyl phthalate, 3-phenoxybenzoic acid, cis-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acid, and for 3,5,6-trichloro-2-pyridinol. The levels of 4,4’dichloro-diphenyl-dichloro-ethylene and glyphosate were also significant although some heavily exposed populations showed higher level of contamination. In contrast, the investigated population of Kinshasa was found to weakly exposed to other pollutants like bisphenol A, dialkyl phosphates, polychlorinated biphenyls, brominated flame retardants, phenolic organo-halogens, and perfluoroalkyl substances.ConclusionAlthough the biologic fluids were collected from a limited number of volunteers (n = 15), the results of the present report clearly indicate that the population of Kinshasa is not spared by the investigated environmental pollutants.Trial registration: this study was retrospectively registered by the national health ethics committee in the Congo under the series number of 159/CNES/BN/PMMF/2020.
Background Environmental pollutants are known to be ubiquitous and may present toxic effects (endocrine-disruption properties, carcinogenicity …) and represent a real threat to human health. The aim of the present pilot study was to assess the content of environmental pollutants (inorganic, persistent, and non-persistent pollutants) in biological samples (urine, serum, and whole blood), collected from volunteers in Kinshasa, capital of Democratic Republic of Congo, in order to identify pollutants of interest and to design a protocol for a larger scale study. Methods From randomly selected 15 volunteers living in Kinshasa, aged from 25 to 66 years, (mean age = 43.4 years), including 10 men and 5 women, urine, whole blood, and serum samples were used in this study to estimate the contents in these environmental pollutants, using inductively coupled plasma mass spectrometry, gas chromatography coupled to mass spectrometry, and liquid chromatography coupled to mass spectrometry. Results When compared to data nationally and internationally available, the preliminary outcomes of this study indicated a very high level of exposure to environmental pollutants in the population of Kinshasa, especially for heavy metals, parabens and triclosan. To a lesser extent, contamination measured for glyphosate, phthalates, organochlorine pesticides, pyrethroids and dialkylphosphate pesticides was also significant. In contrast, the investigated population of Kinshasa was found to be weakly exposed to other persistent organic pollutants like polychlorinated biphenyls, brominated flame retardants, phenolic organohalogens, and perfluoroalkyl substances. Conclusion Although the biologic fluids were collected from a limited number of volunteers (n = 15), the results of the present report clearly indicate that the population of Kinshasa is not spared by the investigated environmental pollutants. Moreover, this study gives us important information to design a larger scale study protocol.
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