Capillary electrophoresis enantioseparation

L Ma, J Han, H Wang, J Gu, R Fu. Capillary electrophoresis enantioseparation of drugs using (3-cyclodextrin polymer Intramolecular synergistic effect. Electrophoresis 20 1900-1903, 1999. 

Scriba GKE. Cyclodextrins in capillary electrophoresis enantioseparations ecent developments and applications. J. Sep. Sci. 2008 31 1991 2011. 

This review provides an overview of the literature published to date on macrocyclic antibiotics exploited for enantioselective separations in high-performance liquid chromatography (HPLC). It was not intended as a comprehensive issue on the applications of such antibiotics in sub- and supercritical fluid chromatography (SFC), thin layer chromatography (TLC), capillary electrophoresis (CE), and capillary electrochromatography (CEC). A number of structural properties of the most important macrocyclic antibiotics applied in HPLC enantioseparations are listed in Table 2.1. 

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. 

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

Cherkaoui, S., and Veuthey, J. L. (2001). Use of negatively charged cyclodextrins for the simultaneous enantioseparation of selected anesthetic drugs by capillary electrophoresis-mass spectrometry. /. Pharm. Biomed. Anal. TJ, 615 — 626. 

Capillary electrophoresis has been applied for the enantioselective determination of the binding constants of chiral drugs with cyclodextrins for basically the following two reasons (1) optimization of chiral selector concentration and (2) understanding the fine mechanisms of enantioseparations in CE. The first group of studies have been published mainly on the early stage of chiral CE development, whereas the second goal is followed in the most recent studies, mainly by Rizzi and Kremser (10,13) and Scriba et al. 

B Chankvetadze, M Fillet, N Burjanadze, D Bergenthal, C Bergander, H Luft-mann, J Crommen, G Blaschke. Enantioseparation of aminoglutethimide with cyclodextrins in capillary electrophoresis and studies of selector-selectand interactions using NMR spectroscopy and electrospray ionization mass spectrometry. Enantiomer 5 313-322, 2000. 

Enantioseparation of dihydropyridine derivatives could be accomplished using capillary electrophoresis by means of neutral and negatively charged (3-cyclodextrin derivatives [40]. The method used a fused silica capillary (47 cm x 75 pm 40 cm to detector), operated at 25°C. The running phase was 50 mM phosphate buffer (pH 3) containing cyclodextrins and organic modifiers, and an applied voltage of 6-20 kV was applied. Detection was effected at 190-300 nm. 

The majority of enantioseparations are performed by pressure-driven liquid chromatography. However, in the last decade other liquid-phase separation techniques have evolved and demonstrated their usefulness for enantioseparations, including supercritical fluid chromatography (SFC), capillary electrophoresis (CE), micellar electrokinetic chromatography (MEKC), and open-tubular and packed-bed electrochromatography (OT-EC and CEC). 

TLC has also been used for the separation of diastereomeric derivatives of enantiomers, but this form of chromatography has not attained widespread use in indirect resolutions. Other chromatographic techniques, for example, supercritical fluid chromatography, capillary electrophoresis, countercurrent chromatography, etc., have not received much attention in indirect enantioseparation. 

For enantioseparation on CSPs in CEC, nonstereospecific interactions, expressed as 4>K, contribute only to the denominator as shown in Eq. (1), indicating that any nonstereospecific interaction with the stationary phase is detrimental to the chiral separation. This conclusion is identical to that obtained from most theoretical models in HPLC. However, for separation with a chiral mobile phase, (pK appears in both the numerator and denominator [Eq. (2)]. A suitable (f)K is advantageous to the improvement of enantioselectivity in this separation mode. It is interesting to compare the enantioselectivity in conventional capillary electrophoresis with that in CEC. For the chiral separation of salsolinols using /3-CyD as a chiral selector in conventional capillary electrophoresis, a plate number of 178,464 is required for a resolution of 1.5. With CEC (i.e., 4>K = 10), the required plate number is only 5976 for the same resolution [10]. For PD-CEC, the column plate number is sacrificed due to the introduction of hydrodynamic flow, but the increased selectivity markedly reduces the requirement for the column efficiency. 

Capillary electrophoresis and its most popular hybrid technique - capillary electrochromatography - are complementary to HPLC, offering rapid analysis, low consumption of sample and solvents, and usually a higher efficiency of separation (due to a larger number of theoretical plates). Similar to HPLC, enantioseparation with the use of electrophoretic methods can be conducted by direct (chiral phase... 

Zhou, L. Thompson, R. French, M. Ellison, D. Wyvratt, J. Simultaneous enantioseparation of a basic drug compound and its acidic intermediate by capillary electrophoresis. J. Sep. Sci. 2002, 25, 1183-1189. 

Capillary electrophoresis (CE) is one of the most promising microanalytical separation techniques for enantiomers. Chiral CE which has had 20 years of development [41] offers some interesting advantages warranting further expansion of this technique in the field of analytical enantioseparation. 

Meyring, M. Chankvetadze, B. Blaschke, G. Enantioseparation of thalidomide and its hydroxylated metabolites using capillary electrophoresis with various cyclodextrins and their combinations as chiral buffer additives. Electrophoresis 1999, 20, 2425-2431. 

Denola N.L., Quiming N.S., Catabay A.R, Saito Y, Jinno K., Optimization of capillary electrophoretic enantioseparation for basic drugs with native beta-CD as a chiral selector. Electrophoresis, 27, 2367-2375 (2006). 

Blanco M., Valverde L, Choice of chiral selector for enantioseparation by capillary electrophoresis. Trends Anal. Chem., 22, 428-439 (2003). 

Fillet M., Hubert R, Crommen J., Method development strategies for the enantioseparation of drugs by capillary electrophoresis using cyclodextrins as chiral additives. Electrophoresis, 19, 2834-2840 (1998). 

Park H., Lee S., Kang S., Jung Y, Jung S., Enantioseparation using sulfated cyclosophoraoses as a novel chiral additive in capillary electrophoresis. Electrophoresis, 25, 2671-2674 (2004). 

Chankvetadze B., Burjanadze N., Blaschke G, Enantioseparation of eryf/tro-mefloquine and its analogues in capillary electrophoresis. J. Pharm. Biomed. Anal, 32, 41 9 (2003). 

Guo L., Lin S.J., Yang YE, Qi L., Wang M.X., Chen Y, Fast enantioseparation of arylglycine amides by capillary electrophoresis with highly sulfated-P-cyclodextrin as a chiral selector. J. Chromatogr. A,... 

Gomez-Gomar A., Ortega E., Calvet C., Andaluz B., Merc R., Frigola J., Enantioseparation of basic pharmaceutical compounds by capillary electrophoresis using sulfated cyclodextrins Application to E-6006, a novel antidepressant. J. Chromatogr. A, 990, 91-98 (2003). 

Kodama, S., Yamamoto, A., Ohura, T., Matsunaga, A., and Kanbe, T., Enantioseparation of imazalil residue in orange by capillary electrophoresis with 2-hydroxypropyl-a-cyclodextrin as a chiral selector, J. Agric. Food Chem., 51, 6128, 2003. 

Lipka, E. Len, C. RabUler, C. Bonte, J.-P. Vaccher, C. Enantioseparation of cis and trans nucleosides, aromatic analogues of stavudine, by capillary electrophoresis and high-performance hquid chromatography. J. Chromatogr. A, 2006,1132, 141 147. 

Since first demonstration in 1994 of the potential use of macrocyclic antibiotics as chiral selectors in analysis, glycopeptide antibiotics have been successfully applied for enantiomer separations by liquid chromatography, as recognition components of chiral stationary phases, and by capillary electrophoresis (CE) as soluble chiral selec-tors. Four chiral stationary phases for chromatography with the selectors vancomycin, ristocetin, teicoplanin, and the teicoplanin aglycone are commercialized under the trade name Chirobiotic by Astec and Supelco. Various aspects of analytical applications of glycopeptide antibiotics have been extensively covered in the recent reviews cited above. As an example. Table 2 shows some representative results for CE enantioseparations with vancomycin, ristocetin A, and teicoplanin, which were taken from Ref. 39. 

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