Enantioseparation of citalopram enantiomers by capillary electrophoresis: Method development through experimental design and computational modeling.

Citalopram (CIT) is a frequently used modern antidepressant that inhibits selectively serotonin reuptake in the brain. It has a chiral center in its structure and is used in therapy as both racemic mixture and pure enantiomer as its pharmacological effect is almost entirely associated with S-CIT. The aim of this study was the development of a simple and rapid capillary electrophoresis (CE) method for the separation and quantification of CIT enantiomers. To establish the optimum chiral selector, several native and derivatized, neutral, and ionized cyclodextrins (CDs) were examined at different pH levels. An experimental design strategy was adopted for method optimization; a fractional factorial design was applied for screening purposes to identify significant experimental factors followed by a face-centered central composite design used for optimization purposes. Computational modeling was used to obtain information on the interaction energy and the geometry of the complexes to aid in the understanding of chiral separation mechanism. The best results were obtained when using a 25-mM phosphate buffer at pH 7.0, 3-mM CM-ß-CD as chiral selector, 17.5°C temperature, 15-kV voltage, and 50 mbar/s hydrodynamic injection. The separation time was fast, below 3 min, and the migration order was S-CIT followed by R-CIT. The analytical performance of the method was verified in terms of precision, linearity, accuracy, sensibility, and robustness, and the method was applied for the determination of CIT enantiomers from pharmaceutical preparations.

Chiral discrimination of amlodipine from pharmaceutical products using capillary electrophoresis

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 ºC, + 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.

Cyclodextrine screening for the chiral separation of carvedilol by capillary electrophoresis.

Carvedilol is administered as a racemic mixture of the R(+)- and S(-)-enantiomers, although it was demonstrated that the two enantiomers exhibit different pharmacological effects and stereoselective pharmacokinetics. The aim of this study was the evaluation of several native and derivatized cyclodextrines as chiral selectors for the separation of carvedilol enantiomers. Stereoselective interactions were observed with four cyclodextrines (ß-CD, hydroxypropyl-ß-CD, randomly methylated ß-CD and sulfobuthyl ether- ß-CD). The effects of CD concentration, pH value and composition of the background electrolyte, capillary temperature, running voltage and injection parameters have been investigated. The method was validated for precision of peak-area response, linearity range and limits of detection and quantification. An efficient stereoselective capillary zone electrophoretic method was developed for the determination of carvedilol enantiomers using a simple 25 mM phosphate buffer at a pH = 2.5 and 10 mM ß-CD as chiral selector, resulting in baseline separation of the two enantiomers with sharp peaks and relatively short analysis time. Highly satisfactory results were obtained from the analysis of carvedilol from tablets, indicating that the method is suitable for routine analysis of carvedilol in pharmaceutical products.

Cyclodextrine screening for the chiral separation of amlodipine enantiomers by capillary electrophoresis.

PURPOSE: Amlodipine is a long acting, dihydropyridine type calcium channel blocker frequently used in the treatment of hypertension and coronary insufficiency. The calcium channel blocking activity resides primarily in the S-amlodipine enantiomer, while R-amlodipine is a potent inhibitor of smooth muscle cell migration. METHODS: In this study capillary electrophoresis was applied for the enantiomeric separation of amlodipine using different native and derivatized; neutral and charged cyclodextrines as chiral selectors. The effects of pH and composition of the background electrolyte, concentration and type of chiral selector, capillary temperature, running voltage and injection parameters have been investigated. RESULTS: Stereoselective interactions were observed when using α-CD, ß-CD, HP-ß-CD, RAMEB, CM-ß-CD and SBE-ß-CD. Optimized separation conditions consisted on a 50 mM phosphate buffer, pH - 3.0, 20 mM RAMEB as chiral selector, + 25 kV applied voltage, 15°C temperature and UV detection at 238 nm. Using the optimized electrophoretic conditions we succeeded the chiral separation of amlodipine enantiomers in approximately 6 minute, the order of migration being R-amlodipine followed by S-amlodipine. The method was successfully applied for the determination of amlodipine enantiomers from commercially available pharmaceuticals. The linearity range, limits of detection and quantification, precision and accuracy were determined and the results obtained confirmed that the method was suitable for this purpose. CONCLUSION: It can be concluded that the proposed capillary electrophoresis methods can be useful for routine pharmaceutical applications with benefits of its effectivity, simplicity, short analysis time and low consumption of analytes, solvents and chiral selectors.

Chiral separation of indapamide enantiomers by capillary electrophoresis.

PURPOSE: Indapamide is probably the most frequently prescribed diuretic drug, generally being used for the treatment of hypertension. It contains a chiral center in its molecule; is marketed as a racemic mixture; but there are rather few studies regarding the pharmacokinetic and the pharmacological effect differences of the two enantiomers. Our aim was the development of a simple, rapid and precise analytical procedure for the chiral separation of indapamide enantiomers. METHODS: In this study capillary zone electrophoresis was used for the enantiomeric separation of indapamide using a systematic screening approach involving different native and derivatized; neutral and charged cyclodextrines as chiral selectors. The effects of pH value and composition of the background electrolyte, capillary temperature, running voltage and injection parameters have been investigated. RESULTS: After preliminary analysis a charged derivatized CD, sulfobuthyl ether- ß-CD, proved to be the optimum chiral selector for the enantioseparation. Using a buffer solution containing 25 mM disodium hydrogenophosphate - 25 mM sodium didydrogenophosphate and 5 mM sulfobuthyl ether- ß-CD as chiral selector at a pH - 7, a voltage of + 25 kV, temperature 15°C and UV detection at 242 nm, we succeeded in the separation of the two enantiomers in approximately 6 minutes, with a resolution of 4.30 and a separation factor of 1.08. CONCLUSION: Capillary zone electrophoresis using cyclodextrines as chiral selectors proved to be a suitable method for the enantioseparation of indapamide. Our method is rapid, specific, reliable, and cost-effective and can be proposed for laboratories performing indapamide routine analysis.