Capillary electrophoresis chiral selectors

GM Beck, SH Neau. A-carrageenan A novel chiral selector for capillary electrophoresis. Chirality 8 503-510, 1996. 

Hui, F. (2004) High Performance Liquid Chromatography and Capillary Electrophoresis Chiral Recognition Mechanisms Using Glycopeptide Macrocyclic Antibiotics as Selectors, Fenxi Huaxue 32, 964-968. 

Catechin and epicatechin are two flavanols of the catechin family. They are enantiomers. The capillary zone electrophoresis (CE) methods with UV-detection were developed for quantitative determination of this flavanols in green tea extracts. For this purpose following conditions were varied mnning buffers, pH and concentration of chiral additive (P-cyclodextrin was chosen as a chiral selector). Borate buffers improve selectivity of separation because borate can make complexes with ortho-dihydroxy groups on the flavanoid nucleus. 

Capillary electrophoresis employing chiral selectors has been shown to be a useful analytical method to separate enantiomers. Conventionally, instrumental chiral separations have been achieved by gas chromatography and by high performance liquid chromatography.127 In recent years, there has been considerable activity in the separation and characterization of racemic pharmaceuticals by high performance capillary electrophoresis, with particular interest paid to using this technique in modem pharmaceutical analytical laboratories.128 130 The most frequently used chiral selectors in CE are cyclodextrins, crown ethers, chiral surfactants, bile acids, and protein-filled... 

Nishi et al. [110] used dextran and dextrin as chiral selectors in capillary-zone electrophoresis. Polysaccharides such as dextrins, which are mixtures of linear a-(l,4)-linked D-glucose polymers, and dextrans, which are polymers of D-glucose units linked predominantly by a-(l,6) bonds, have been employed as chiral selectors in the capillary electrophoretic separation of enantiomers. Because these polymers are electrically neutral, the method is applicable to ionic compounds. The enantiomers of basic or cationic drugs such as primaquine were successfully separated under acidic conditions. The effects of molecular mass and polysaccharide concentration on enantioselectivity were investigated. 

Phinney et al. [Ill] investigated the application of citrus pectins, as chiral selectors, to enantiomer separations in capillary electrophoresis. Successful enantioreso-lution of primaquine and other antimalarials, was achieved by utilizing potassium polypectate as the chiral selector. Changes in pH, chiral additive concentration, and capillary type were studied in relation to chiral resolution. The effect of degree of esterification of pectin materials on chiral recognition was evaluated. 

With capillary electrophoresis (CE), another modern primarily analytically oriented separation methodology has recently found its way into routine and research laboratories of the pharmaceutical industries. As the most beneficial characteristics over HPLC separations the extremely high efficiency leading to enhanced peak capacities and often better detectability of minor impurities, complementary selectivity profiles to HPLC due to a different separation mechanism as well as the capability to perform separations faster than by HPLC are frequently encountered as the most prominent advantages. On the negative side, there have to be mentioned detection sensitivity limitations due to the short path length of on-capillary UV detection, less robust methods, and occasionally problems with run-to-run repeatability. Nevertheless, CE assays have now been adopted by industrial labs as well and this holds in particular for enantiomer separations of chiral pharmaceuticals. While native cyclodextrins and their derivatives, respectively, are commonly employed as chiral additives to the BGEs to create mobility differences for the distinct enantiomers in the electric field, it could be demonstrated that cinchona alkaloids [128-130] and in particular their derivatives are applicable selectors for CE enantiomer separation of chiral acids [19,66,119,131-136]. 

Aboul-Enein, H.Y. and Ali, I., Macrocyclic antibiotics as effective chiral selectors for enantiomeric resolntion by liquid chromatography and capillary electrophoresis, Chromatographia, 52, 679, 2000. 

Ward, T.J., Dann III, C., and Blaylock, A., Enantiomeric resolution using the macrocyclic antibiotics rifamycin B and rifamycin SV as chiral selectors for capillary electrophoresis, J. Chromatogr. A, 715, 337, 1995. 

Strege, M.A., Huff, B.E., and Risley, D.S., Evaluation of macrocyclic antibiotic A82846B as a chiral selector for capillary electrophoresis separations, LC-GC, 14, 144, 1996. 

Tesafova, E., Bosdkovd, Z., and Zuskova, L, Enantioseparation of selected iV-tert-butyloxycarbonyl amino acids in high-performance liquid chromatography and capillary electrophoresis with a teicoplanin chiral selector. J. Chromatogr. A, 879, 147, 2000. 

Perrin, C., Vander Heyden, Y, Maftouh, M., Massart, D.L. Rapid screening for chiral separations by short-end injection capillary electrophoresis nsing highly sulfated cyclodextrins as chiral selectors. Electrophoresis 2001, 22, 3203-3215. 

Chiral separation of drng molecules and of their precursors, in the case of synthesis of enantiomerically pure drugs, is one of the important application areas of HPLC in pharmaceutical analysis. Besides HPLC, capillary electrophoresis (CE) is another technique of choice for chiral separations. Chapter 18 provides an overview of the different modes (e.g., direct and indirect ones) of obtaining a chiral separation in HPLC and CE. The direct approaches, i.e., those where the compound of interest is not derivatized prior to separation, are discussed in more detail since they are cnrrently the most frequently used techniques. These approaches require the use of the so-called chiral selectors to enable enantioselective recognition and enantiomeric separation. Many different molecnles have been nsed as chiral selectors, both in HPLC and CE. They can be classified into three different groups, based on their... 

The aim of this chapter is to give an overview of chiral separations of pharmaceutical compounds by means of HPLC. Capillary electrophoresis, which is the most popular technique besides HPLC for performing chiral separations at the analytical level, will also be briefly discussed. A second reason to discuss chiral separation in CE in short is the large overlap in the chiral selectors applied in both techniques. 

Chankvetadze, B., and Blaschke, G. (1999). Selector-selectand interactions in chiral capillary electrophoresis. Electrophoresis 20, 2592—2604. 

Tanaka, Y., and Terabe, S. (1997). Separation of the enantiomers of basic drugs by affinity capillary electrophoresis using a partial filling technique and ai-acid glycoprotein as chiral selector. 

Amini, A., Pettersson, C., and Westerlund, D. (1997). Enantioresolution of disopyramide by capillary affinity electrokinetic chromatography with human alphal-acid glycoprotein (AGP) as chiral selector applying a partial filling technique. Electrophoresis 18, 950—957. 

Armstrong, D. W., and Nair, U. B. (1997). Capillary electrophoretic enantioseparations using macrocyclic antibiotics as chiral selectors. Electrophoresis 18, 2331—2342. 

Eanali, S., Desiderio, C., Schulte, G., Heitmeier, S., Strickmann, D., Chankvetadze, B., and Blaschke, G. (1998). Chiral capillary electrophoresis-electrospray mass spectrometry coupling using vancomycin as chiral selector. /. Chromatogr. A 800, 69—76. 

Rudaz, S., Calleri, E., Geiser, L., Gherkaoui, S., Prat, J., and Veuthey, J. L. (2003). Infinite enantiomeric resolution of basic compounds using highly sulfated cyclodextrin as chiral selector in capillary electrophoresis. Electrophoresis 24, 2633—2641. 

G Schulte, S Heitmeier, B Chankvetadze, G Blaschke. Chiral capillary electrophoresis-electrospray mass spectrometry coupling with charged cyclodextrin derivatives as chiral selectors. J Chromatogr A 800 77-82, 1998. 

B Chankvetadze, G Endresz, G Blaschke. Charged cyclodextrin derivatives as chiral selectors in capillary electrophoresis. Chem Soc Rev 25 141-146,... 

T Schmitt, H Engelhardt. Charged and uncharged cyclodextrins as chiral selectors in capillary electrophoresis. Chromatographia 37 475-481, 1993. 

Y Tanaka, S Terabe. Enantiomer separation of acidic racemates by capillary electrophoresis using cationic and amphoteric f -cyclodextrins as chiral selectors. J Chromatogr A 781 151-160, 1997. 

G Galaverna, R Corradini, A Dossena, R Marchelli. Histamine-modified cationic /3-cyclodextrins as chiral selectors for the enantiomeric separation of hydroxy acids and carboxylic acids by capillary electrophoresis. Electrophoresis 20 2619-2629, 1999. 

S Fanali, P Bocek. A practical procedure for the determination of association constants of the analyte—chiral selector equilibria by capillary zone electrophoresis. Electrophoresis 17 1912-1924, 1996. 

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