Capillary enantioseparation

In 1992 Mayer and Schurig showed for the first time the possibility of enantioseparations in open tubular capillaries modified with a permethylated CyD derivative. This technique was used later with different chiral selectors but did not mature to become the method of choice for CEC enantioseparations, most likely due to the following conflict inherent in this technique. For a separation which occurs on the mobile phase/stationary phase interface and not in the bulk solution, retention of the analyte on the capillary wall (chiral stationary phase) is necessary for achieving a separation. On the other hand, any retentive analyte-capillary wall interactions are associated with a drastic decrease in peak efficiency in capillary electromigration techniques. However, this study stimulated research in both capillary enantioseparation techniques and in the use of CyD-based CSPs for CEC enantioseparations. 

Chankvetadze, B., Yamamoto, C., Tanaka, N., Nakanishi, K., Okamoto, Y. (2004). High-performance liquid chromatographic enantioseparations on capillary columns containing monolithic silica modified with cellulose tris(3,5-dimethylphenylcarbamate). J. Sep. Sci. 27, 905-911. 

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. 

Schmid, M.G, et al., Enantioseparation of dipeptides by capillary electrochromatography on a teicoplanin aglycone chiral stationary phase, J. Chromatogr. A., 990, 83, 2003. 

Some special approaches defined in the CE enantioseparation field can be found in References 37 and 38. In Reference 37, the authors tested four approaches to decrease the analysis time of a previously developed chiral separation method for amphetamine and its related compounds. The considered possibilities were (i) the short-end injection technique or (ii) increased electrical field combined with a capillary length reduction. 

Mangelings, D., Hardies, N., Maftouh, M., Suteu, C., Massart, D.L., Vander Heyden, Y. Enantioseparations of basic and bifunctional compounds by capillary electrochromatography using polysaccharide stationary phases. Electrophoresis 2003, 24, 2567-2576. 

Chankvetadze, B. (1999). Recent trends in enantioseparations using capillary electromigration techniques. Trends Anal. Chem. 18, 485—498. 

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. 

Zheng, J., and Shamsi, S. A. (2006). Simultaneous enantioseparation and sensitive detection of eight p-blockers using capillary electrochromatography-electrospray ionization-mass spectrometry. Electrophoresis 27, 2139—2151. 

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. 

AM Rizzi, L Kremser. pKa shift-associated effects in enantioseparations by cyclodextrin-mediated capillary zone electrophoresis. Electrophoresis 20 2715-2722, 1999. 

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. 

Fig. 3 Enantioseparation of ( )-CL with (a) 1 mg/mL HDAS-/3-CD, and (b) 18 mg/mL /3-CD. The separation capillary was fused silica with 40/47 cm effective/ total length and 50 /am I.D. Detection was performed at the cationic side of the capillary. Applied voltage 20 kV 100 mM phosphate-TEA buffer, pH 3.0. UV detection (214 nm). (Reproduced with permission from Ref. 65.)...

B Chankvetadze, G Blaschke. Enantioseparations in capillary electromigration techniques recent developments and future trends. J Chromatogr A 906 309-363, 2001. 

S Cladrowa-Runge, A Rizzi. Enantioseparations of 6-aminoquinolyl-lV-hydrox-ysuccinimidyl carbamate derivatized amino acids by capillary zone electrophoresis using native and substituted /3-cyclodextnns as chiral additives II. Evaluation of complexation constants. J Chromatogr A 759 167-175, 1997. 

B Chankvetadze, I Kartozia, N Burjanadze, D Bergenthal, H Luftmann, G Blaschke. Enantioseparation of chiral phenothiazine derivatives in capillary... 

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. 

A Amini, U Paulsen-Sorman. Enantioseparation of local anaesthetic drugs by capillary zone electrophoresis with cyclodextrins as chiral selectors using a partial-filling technique. Electrophoresis 18 1019-1025, 1997. 

The progress toward enantiomerically pnre drngs makes the selective and rapid analysis of enantiomers an important issue, both for chiral parity determinations and for enantioselective bioanalysis. Chankvetadze et al. [198] performed enantioseparations within an analysis time of 1 min for each of two chiral compounds (1,2,2,2-tetraphenylethanol and 2,2 -dihydroxy-6,6 -dimethylbiphenyl) by nsing a homemade capillary column containing monolithic silica modified with amylose tris(3,5-dimethylphenylcarbamate) (Figure 17.10). 

Olsson and Blomberg [141] enantioseparated omeprazole and its metabolite 5-hydroxyomeprazole using open tubular capillary electrochromatography with immobilized avidin as chiral selector. The separation was performed with open tubular capillary electrochromatography. The protein avidin was used as the chiral selector. Avidin was immobilized by a Schiffs base type of reaction where the protein was via glutral-dehyde covalently bonded to the amino-modified wall of a fused-silica capillary, 50 /an i.d. Both racemates were baseline resolved. Resolution... 

Girod, M., Chankvetadze, B., and Blaschke, G. (2000) Enantioseparations in non-aqueous capillary electrochromatography using polysaccharide type chiral stationary phases, J. Chromatogr. A 887, 439-455. 

The importance of tailoring surface chemistry was first demonstrated by three different monolithic capillary columns that were prepared by directly incorporating of the chiral monomer 2-hydroxyethyl methacrylate ([Pg.239]

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. 

Figure 35 CEC enantioseparations of 2-(benzylsulfinyl)benzamide in capillaries packed with derivitized with differing amounts of the polysaccharide derivative cellulose tris(3,5-dichlorophenylcarbamate). The stationary phase contained (a) 4.8%, (b) 1.0%, and (c) 0.5% (w/w) of the chiral selector. (Reprinted from Ref. 1 56, with permission.)...

A polar stationary phases such as ODS and TMS and polar such as CN, diol, or NO2 have been successfully applied to the separation of monosaccharides Separation of maltodextrin derivatized with trifluoroacetic anhydride using FID and a CN packed column Capillary supercritical fluid chromatography-MS is well suited to confirm the identity of the TMS derivative of inositol triphosphate Chiral analytes Enantioseparation... 

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