Capillary electrophoresis chiral separation

Apryll M. Stalcup received her PhD in chemistry (1988) from Georgetown University in Washington, DC. After postdoctoral training at the University of Missouri-Rolla, she joined the Department of Chemistry at the University of Hawaii-Manoa in 1990 as an assistant professor. She moved to the Chemistry Department at the University of Cincinnati as an associate professor in 1996 and was promoted as a professor in 2002. Her research interests include liquid chromatography, capillary electrophoresis, chiral separations, and investigations of separation mechanisms. 

F Wang, MG Khaledi. Non-aqueous capillary electrophoresis chiral separations with sulfated beta-cyclodextrins. J Chromatogr B 731 187-197, 1999. 

Wang F, Khaledi M (1998) Nonaqueous capillary electrophoresis chiral separations with quaternary ammonium P-cyclodextrin. J Chromatogr A 817 121-128... 

M. M. Rogan, K. D. Altria, and D. M. Goodall, Enantioselective separations using capillary electrophoresis, Chirality 6-.25 (1994). 

Evans C.E., Stalcup A.M., Comprehensive strategy for chiral separations using sulfated cyclodextrins in capillary electrophoresis. Chirality, 15, 709-723 (2003). 

Tesrfovd, E., SevCik, J., Gas, B., and Armstrong, D.W., Effects of partial/asymmetrical filling of micelles and chiral selectors on capillary electrophoresis enantiomeric separation Generation of a gradient. Electrophoresis, 25, 2693, 2004. 

Cardoso, C. D., labor, V. A. R, andBonato, P. S., Capillary electrophoretic chiral separation of hydroxychloroquine and its metabolites in the microsomal fraction of liver homogenates. Electrophoresis, 27, 1248-1254, 2006. 

Jiang C, Tong MY, Armstrong DW, Perera S, Bao Y, MacDonnell FM (2009) Enantiomeric separation of chiral ruthenium(II) complexes using capillary electrophoresis. Chirality 21 208-217... 

Francotte E, Cherkaoui S, Faupel M (1993) Separation of the enantiomers of some racemic nonsteroidal aromatase inhibitors and barbiturates by capillary electrophoresis. Chirality 5 516-526... 

Bergholdt BA, Lehmann SV (1998) High-speed separation of ormeloxifene enantiomers using sulfated P-cyclodextrin in capillary electrophoresis. Chirality 10 699-704... 

Abstract Target-specific chiral selectors, which are characterized by a predictable elution order depending on the target enantiomer empioyed for the selection of the chirai selector, have recently received much attention in the enantioselective analysis fieid. In this context, bioaffinity-based molecular recognition toois such as nucleic acid aptamers have notabiy demonstrated very attractive features for the chiral discrimination of active moiecuies. In this chapter, the enantioseiective properties of aptamer chiral selectors and the major factors that control and modulate the liquid chromatography and capillary electrophoresis enantiomer separation are addressed. 

Capillary Electrophoresis. Capillary electrophoresis (ce) or capillary 2one electrophoresis (c2e), a relatively recent addition to the arsenal of analytical techniques (20,21), has also been demonstrated as a powerful chiral separation method. Its high resolution capabiUty and lower sample loading relative to hplc makes it ideal for the separation of minute amounts of components in complex biological mixtures (22,23). 

Enantioresolution in capillary electrophoresis (CE) is typically achieved with the help of chiral additives dissolved in the background electrolyte. A number of low as well as high molecular weight compounds such as proteins, antibiotics, crown ethers, and cyclodextrins have already been tested and optimized. Since the mechanism of retention and resolution remains ambiguous, the selection of an additive best suited for the specific separation relies on the one-at-a-time testing of each individual compound, a tedious process at best. Obviously, the use of a mixed library of chiral additives combined with an efficient deconvolution strategy has the potential to accelerate this selection. 

Chiral additives have been shown to be very effective for chiral separations by capillary electrophoresis (CE) [4, 5]. Indeed, it may be argued that there has been considerably more research activity in chiral separations by CE than by EC methods since the introduction of the former technique. Chiral additives in CE have several advantages, some of which are highlighted in Table 11-2. 

High performance capillary electrophoresis in its current form is a new technique. Its feasibility has been proven by the analysis and separation of small ions, drugs, chiral molecules, polymers, and biopolymers.93 We are learning more every day about the small tricks of the trade of the technique, and the efficiency and reproducibility of the methods are improving. 

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... 

Vespalec, R. and Bocek, P., Chiral separations by capillary electrophoresis present state of the art, Electrophoresis, 15, 755, 1994. 

Miniaturized columns have provided a decisive advantage in speed. Uracil, phenol, and benzyl alcohol were separated in 20 seconds by CEC in an 18 mm column with a propyl reversed phase.29 A19 cm electrophoretic channel was etched into a glass wafer, filled with a y-cyclodextrin buffer, and used to resolve chiral amino acids from a meteorite in 4 minutes.30 A 6 cm channel equipped with a syringe pump to automate sample derivatization was used to separate amino acids modified with fluorescein isothiocyanate.31 Nanovials have been used to perform tryptic digests on the 15 nL scale for subsequent separation on capillary Electrophoresis.32 A microcolumn has also been used to generate fractions representing time-points of digestion from a 40 pL sample.33 A disposable nanoelectrospray emitter has been... 

Kang, J. and Ou, Q., Chiral separation of racemic mexilitine hydrochloride using cyclodextrins as chiral additive by capillary electrophoresis,. Chromatogr. A, 795, 394, 1998. 

Huang, Y.S., Liu, J.T., Lin, L.C., and Lin, C.H., Chiral separation of 3,4-methylenedioxymeth-amphetamine and related compounds in clandestine tablets and urine samples by capillary electro-phoresis/fluorescence spectroscopy, Electrophoresis 24(6), 1097-1104, 2003. 

Lin et al. [95] used capillary electrophoresis with dual cyclodextrin systems for the enantiomer separation of miconazole. A cyclodextrin-modified micellar capillary electrophoretic method was developed using mixture of /i-cyclodextrins and mono-3-0-phenylcarbamoyl-/j-cyclodextrin as chiral additives for the chiral separation of miconazole with the dual cyclodextrins systems. The enantiomers were resolved using a running buffer of 50 mmol/L borate pH 9.5 containing 15 mmol/L jS-cyclodextrin and 15 mmol/L mono-3-<9-phcnylcarbamoyl-/j-cyclodextrin containing 50 mmol/L sodium dodecyl sulfate and 1 mol/L urea. A study of the respective influence of the /i-cyclodcxtrin and the mono-3-(9-phenylcarbamoyl-/i-cyclodextrin concentration was performed to determine the optical conditions with respect to the resolution. Good repeatability of the method was obtained. 

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. 

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