Streamlined targeting of Amaryllidaceae alkaloids from the bulbs of Crinum scillifolium using spectrometric and taxonomically-informed scoring metabolite annotations.

Four undescribed alkaloids have been isolated from the bulbs of the previously unstudied Crinum scillifolium. These compounds were targeted following a state-of-the-art molecular networking strategy comprising a dereplication against in silico databases and re-ranking of the candidate structures based on taxonomically informed scoring. The unreported structures span across a variety of Amaryllidaceae alkaloids appendages. Their structures were unambiguously elucidated by thorough interpretation of their HRESIMS and 1D and 2D NMR data, and comparison to literature data. DFT-NMR calculations were performed to support the determined relative configurations of scillitazettine and scilli-N-desmethylpretazettine and their absolute configurations were mitigated by comparison between experimental and theoretically calculated ECD spectra. The lack of a methyl group on the nitrogen atom in the structure of scilli-N-desmethylpretazettine series is highly unusual in the pretazettine/tazettine series but the most original structural feature in it lies in its 11α disposed hydrogen, which is new to pretazettines. The antiplasmodial as well as the cytotoxic activities against the human colon cancer cell line HCT116 were evaluated, revealing mild to null activities.

Determination of artemether and lumefantrine in anti-malarial fixed-dose combination tablets by microemulsion electrokinetic chromatography with short-end injection procedure.

BACKGROUND: Artemether-lumefantrine (AL) combination therapy is now the most used anti-malarial treatment in the world. Quality control of AL formulations is still a major challenge in developing countries. Until now, only liquid chromatographic methods have been reported in the literature for their analysis. Capillary electrophoretic methods, which present various advantages (low price of capillary, low volumes of electrolyte consumption), may be an alternative to liquid chromatography methods. In this paper, a reliable method was developed and validated for the determination of AL in commercial fixed-dose combination tablets commercialized in Côte d'Ivoire. METHODS: Artemether and lumefantrine were determined by microemulsion electrokinetic chromatography using short-end injection procedure. The two analytes were extracted from tablets by acidified methanol. Pyrimethamine was used as internal standard. Separation was carried out in an uncoated fused silica capillary, 30 cm long × 50 µm internal diameter, using an effective length of 10 cm and a microemulsion composed of octane, butanol, sodium dodecyl sulfate and borate buffer as background electrolyte, a - 500 V x cm(-1) electric field and a detection wavelength of 214 nm. RESULTS: Artemether, lumefantrine and pyrimethamine were separated in 6 min. The method was reliable with respect to selectivity towards formulation excipients, linearity of the response function (r2 > 0.998), recovery studies from synthetic tablets (in the range 99-101%), repeatability (relative standard deviation 1-3%, n = 7 analytical procedures). Application to four commercial formulations containing 20/120 mg of AL per tablet gave a content in good agreement with the declared content. However, the electropherogram of one tablet formulation showed the presence of an ingredient which was not declared. CONCLUSION: The developed MEEKC method can be proposed as an alternative method to liquid chromatography for the determination of artemether and lumefantrine in fixed-dose combination tablet formulations.

Capillary electrophoresis methods for the analysis of antimalarials. Part II. Achiral separative methods.

An exhaustive review of applications of achiral capillary electrophoresis methods to the analysis of antimalarials is presented. It covers quality control of formulations, analysis in biological fluids and food, determination of physico-chemical properties (pKa, partition coefficient and interaction studies). Miscellaneous applications are also considered.

Capillary electrophoresis methods for the analysis of antimalarials. Part I. Chiral separation methods.

This paper presents an overview on the current status of enantiomeric and diastereomeric separations of chiral antimalarials and derivatives by capillary electrophoresis (CE). The wide variety of chiral selectors which have been employed to resolve successfully antimalarial enantiomers: oligosaccharides (cyclodextrins, oligomaltodextrins), neutral (amylose, dextrin and dextran) and charged (chondroitin sulfate, heparin, dextran sulfate) polysaccharides and proteins are reviewed. Cyclodextrins were the most employed. Chiral additives added to the background electrolyte often facilitated separations of quinine/quinidine and cinchonine/cinchonidine diastereomers. However, in a few cases, using micellar electrokinetic capillary chromatography or non aqueous CE, resolution of diastereomers could be achieved without additives. Quantitative applications of CE to the quality control of antimalarial drugs and their analysis in biological and food matrices are presented.

Capillary electrophoresis for the assay of fixed-dose combination tablets of artesunate and amodiaquine.

BACKGROUND: Quality control of drugs in formulations is still a major challenge in developing countries. For the quality control of artesunate and amodiaquine tablets in fixed-dose combination, only liquid chromatographic methods have been proposed in the literature. There are no capillary electrophoretic methods reported for the determination of these active substances, although this technique presents several advantages over liquid chromatography (long lifetime, low price of the capillary, low volumes of electrolyte consumption) in addition to simplicity. In this paper, a reliable capillary electrophoresis method has been developed and validated for the quality control of these drugs in commercial fixed-dose combination tablets. METHODS: Artesunate and amodiaquine hydrochloride in bilayer tablets were determined by micellar electrokinetic capillary chromatography (MEKC). Analytes were extracted from tablets by sonication with a solvent mixture phosphate buffer pH 7.0-acetonitrile containing benzoic acid as internal standard. Separation was carried out on Beckman capillary electrophoresis system equipped with fused silica capillary, 30 cm long (20 cm to detector) × 50 µm internal diameter, using a 25 mM borate buffer pH 9.2 containing 30 mM sodium dodecyl sulfate as background electrolyte, a 500 V cm(-1) electric field and a detection wavelength of 214 nm. RESULTS: Artesunate, amodiaquine and benzoic acid were separated in 6 min. The method was found to be reliable with respect to specificity,linearity of the calibration line (r(2) > 0.995), recovery from synthetic tablets (in the range 98-102%), repeatability (RSD 2-3%, n = 7 analytical procedures). Application to four batches of commercial formulations with different dosages gave content in good agreement with the declared content. CONCLUSION: The MEKC method proposed is reliable for the determination of artesunate and amodiaquine hydrochloride in fixed-dose combination tablets. The method is well-suited for drug quality control and detection of counterfeit or substandard medicines.

Capillary zone electrophoresis as a potential technique for the simultaneous determination of sulfadoxine and pyrimethamine in tablet formulations.

A novel, simple and rapid capillary zone electrophoresis method with UV detection has been developed for the simultaneous determination of pyrimethamine and sulfadoxine in tablet formulations. The compounds are separated in 6 min in a fused silica capillary, 30 cm long (20 cm to detector)× 50 µm using a 100 mM phosphate buffer pH 7.2 as background electrolyte, a 330 V cm(-1) electric field and a detection wavelength of 214 nm. Analysis of different tablet formulations has shown a good agreement with the liquid chromatography method described in the United States Pharmacopoeia. Main advantages of the CZE method are the rapid set-up of instrumentation and capillary equilibration, short analysis time and low running cost.