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Novel capillary electrophoresis methods using CDs as chiral selectors were developed and validated for the chiral separation of lansoprazole and rabeprazole, two proton pump inhibitors. Fourteen different neutral and anionic CDs were screened at pH 4 and 7 in the preliminary analysis. Sulfobutyl-ether-␤-CD with a degree of substitution of 6.5 and 10 at neutral pH proved to be the most suitable chiral selector for both compounds. Various dual CD systems were also compared, and the possible mechanisms of enantiomer separation were investigated. A dual selector system containing sulfobutyl-ether-␤-CD degree of substitution 6.5 and native ␥ -CD proved to be the most adequate system for the separations. Method optimization was carried out using an experimental design approach, performing an initial fractional factorial screening design, followed by a central composite design to establish the optimal analytical conditions. The optimized methods (25 mM phosphate buffer, pH 7, 10 mM sulfobutyl-ether-␤-CD/20 mM ␥ -CD, +20 kV voltage; 17°C temperature; 50 mbar/3 s injection, detection at 210 nm for lansoprazole; 25 mM phosphate buffer, pH 7, 15 mM sulfobutyl-ether-␤-CD/30 mM ␥ -CD, +20 kV voltage; 18°C temperature; 50 mbar/3 s injection, detection at 210 nm for rabeprazole) provided baseline separation for lansoprazole (R s = 2.91) and rabeprazole (R s = 2.53) enantiomers with favorable migration order (in both cases the S-enantiomers migrates first). The optimized methods were validated according to current guidelines and proved to be reliable, linear, precise, and accurate for the determination of 0.15% distomer as chiral impurity in dexlansoprazole and dexrabeprazole samples.

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A direct HPLC method was developed for the enantioseparation of pantoprazole using macrocyclic glycopeptide-based chiral stationary phases, along with various methods to determine the elution order without isolation of the individual enantiomers. In the preliminary screening, four macrocyclic glycopeptide-based chiral stationary phases containing vancomycin (Chirobiotic V), ristocetin A (Chirobiotic R), teicoplanin (Chirobiotic T), and teicoplanin-aglycone (Chirobiotic TAG) were screened in polar organic and reversed-phase mode. Best results were achieved by using Chirobiotic TAG column and a methanol-water mixture as mobile phase. Further method optimization was performed using a face-centered central composite design to achieve the highest chiral resolution. Optimized parameters, offering baseline separation (resolution = 1.91 ± 0.03) were as follows: Chirobiotic TAG stationary phase, thermostated at 10°C, mobile phase consisting of methanol/20mM ammonium acetate 60:40 v/v, and 0.6 mL/min flow rate. Enantiomer elution order was determined using HPLC hyphenated with circular dichroism (CD) spectroscopy detection. The online CD signals of the separated pantoprazole enantiomers at selected wavelengths were compared with the structurally analogous esomeprazole enantiomer. For further verification, the inline rapid, multiscan CD signals were compared with the quantum chemically calculated CD spectra. Furthermore, docking calculations were used to investigate the enantiorecognition at molecular level. The molecular docking shows that the R-enantiomer binds stronger to the chiral selector than its antipode, which is in accordance with the determined elution order on the column-S-followed by the R-isomer. Thus, combined methods, HPLC-CD and theoretical calculations, are highly efficient in predicting the elution order of enantiomers.

The present work describes the development of a capillary electrophoresis (CE) method for the chiral discrimination of amlodipine (AML) enantiomers using cyclodextrine (CD) derivatives as chiral selectors. A large number of native and derivatized, neutral and ionized CD derivatives were screened to find the optimal chiral selector; and carboximethyl-β-CD (CM-β-CD) was selected for the enantiomeric discrimination. A factorial analysis study was performed by orthogonal experimental design in which several factors were varied at the same time to optimize the separation method. The optimized method (25 mM phosphate buffer, pH = 9.0, 15 mM CM-β-CD, 15 °C, + 25 kV, 30 mbar/1 second, detection wavelength 230 nm) was successfully applied for the baseline separation of AML enantiomers within 5 minutes. Successful validation and application of the proposed CE method suggest its routine use in enantioselective control of AML in pharmaceutical preparations.

Este trabalho descreve o desenvolvimento de um método simples de eletroforese capilar (EC) para determinação simultânea dos três derivados mais frequentemente usados da fluoroquinolona: ciprofloxacina, norfloxacina e ofloxacina. Devido às características estruturais e físico-químicas muito semelhantes, ciprofloxacina e norfloxacina não podem ser separadas pelo método clássico de eletroforese capilar de zona (CZE). Suas separações podem ser resolvidas usando cromatografia eletrocinética micelar (MEKC), adicionando um surfactante aniônico à solução-tampão. A eficiência da separação pode ser intensificada através da otimização de parâmetros analíticos. Um método rápido e confiável foi desenvolvido, e os melhores resultados foram obtidos usando uma solução-tampão contendo tetraborato de sódio 25 mmol L -1 , dodecilsulfato de sódio 100 mmol L -1 e metanol 5% como modificador orgânico.This work describes the development of a simple capillary electrophoresis (CE) method for simultaneous determination of the three most frequently used fluoroquinolone derivatives: ciprofloxacin, norfloxacin and ofloxacin. Due to very similar structural and physicochemical characteristics, ciprofloxacin and norfloxacin cannot be separated by the classic method of capillary zone electrophoresis (CZE). Their separations can be solved using micellar electrokinetic chromatography (MEKC), by adding an anionic surfactant to the buffer solution. The efficiency of the separation can be enhanced through the optimization of analytical parameters. A fast reliable method was developed, and the best results were obtained using a buffer solution containing 25 mmol L -1 sodium tetraborate, 100 mmol L -1 sodium dodecyl sulphate and 5% methanol as organic modifier.