Cyclodextrin liquid chromatography separation

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... 

A. M. Stalcup, Cyclodextrin bonded chiral stationary phases in enantiomer separations in A practical approach to chiral separations by liquid chromatography, G. Subramanian, VCH, Weinheim (1994) Chapter 5. 

P. Jandera, S. Buncekova and J. Planeta, Separation of isomeric naphtalenesulphonic acids by micro high-performance liquid chromatography with mobile phases containing cyclodextrin. 

Pihlainen, K. and Kostiainen, R., Effect of the eluent on enantiomer separation of controlled drugs by liquid chromatography-ultraviolet absorbance detection-electrospray ionisation tandem mass spectrometry using vancomycin and native fi-cyclodextrin chiral stationary phases, J. Chromatogr. A, 1033, 91, 2004. 

CR Mitchell, DW Armstrong. Cyclodextrin-based chiral stationary phases for liquid chromatography A twenty-year overview. In G Gubitz, MG Schmid (Eds.) Chiral Separations, Methods and Protocols, Humana Press Inc., Totowa, NJ Humana Press Inc. 61 pp., 2003. 

Immobilization. The ability of cyclodextrins to form inclusion complexes selectively with a wide variety of guest molecules or ions is well known (1,2) (see Inclusion COMPOUNDS). Cyclodextrins immobilized on appropriate supports are used in high performance liquid chromatography (hplc) to separate optical isomers. Immobilization of cyclodextrin on a solid support offers several advantages over use as a mobile-phase modifier. For example, as a mobile-phase additive, p-cyclodextrin has a relatively low solubility. The cost of y- or a-cyclodextrin is high. Furthermore, when employed in thin-layer chromatography (dc) and hplc, cyclodextrin mobile phases usually produce relatively poor efficiencies. 

In view of the importance of chiral resolution and the efficiency of liquid chromatographic methods, attempts are made to explain the art of chiral resolution by means of liquid chromatography. This book consists of an introduction followed by Chapters 2 to 8, which discuss resolution chiral stationary phases based on polysaccharides, cyclodextrins, macrocyclic glyco-peptide antibiotics, Pirkle types, proteins, ligand exchangers, and crown ethers. The applications of other miscellaneous types of CSP are covered in Chapter 9. However, the use of chiral mobile phase additives in the separation of enantiomers is discussed in Chapter 10. 

Stalcup AM, Cyclodextrin bonded chiral stationary phases in enantiomer separations, in A Practical Approach to Chiral Separations by Liquid Chromatography (Subramanian G, Ed.), VCH Verlag, Weinheim, Germany, p. 95 (1994). 

A Guide to Using Cyclodextrin Bonded Phases for Liquid Chromatography, Advanced Separation Technologies, Inc., Whippany, NJ (1996). 

Eto, S., Noda, H., Noda, A., Chiral Separation of barbiturates and hydantoins by reversed-phase high-performance liquid-chromatography using a 25 or 50 mm short ods cartridge column via beta-cyclodextrin inclusion complexes. J. Chromatogr. 1992, 579, 253-258. 

The preparative-scale separation of enantiomers on chiral stationary phases (CSPs) by GC cannot match the overwhelming success achieved in the realm of liquid chromatography (LC) (Francotte, 1994, 1996 and 2001). Modern commercial instrumentation for preparative-scale GC is not readily available. In contrast to LC, separation factors a in enantioselective GC are usually small (a = 1.01 - 1.20). This is beneficial for fast analytical separations but detrimental to preparative-scale separations. Only in rare instances are large chiral separation factors (a > 1.5) observed in enantioselective GC. Only in one instance, a separation factor as high as a = 10 was detected in enantioselective GC for a chiral fluorinated diether and a modified 7-cyclodextrin (Schurig and Schmidt, 2003) (vide supra). 

Koscielski, T., Sybilska, D., and Jurczak, J. (1983) Separation of a- and / -pinene into enantiomers in gas-liquid chromatography systems via a-cyclodextrin inclusion complexes. J. Chromatogr. 280, 131-134. 

Armstrong, D.W., DeMond, W., and Czech, B.P., Separation of metallocene enantiomers by liquid chromatography chiral recognition via cyclodextrin bonded phases, Anal. Chem., 57, 481, 1985. 

Feitsma, K., Bosman, J., Drenth, B., and DeZeeuw, R., A study of the separation of enantiomers of some aromatic carboxylic acids by high-performance liquid chromatography on a P-cyclodextrin-bonded stationary phase, J. Chromatogr., 333, 59, 1985. 

Sybilska, D., Debowski, J., Jurczak, J., and Zukowski, J., The a- and P-cyclodextrin complexation as a tool for the separation of o-, m- and p-nitro-, cis- and trans-cinnamic acids by reversed-phase high-performance liquid chromatography, J. Chromatgr., 286, 163, 1984. 

K. Shimada, K. Mitamura, M. Morita, and K. Hirakata, Separation of the diastereomers of baclofen by high performance liquid chromatography using cyclodextrin as a mobile phase additive, J. Liquid Chromatogr., 76 15 (1993). 

In high performance liquid chromatography (HPLC), the cyclodextrins (12, 27-36) or highly soluble methylated cyclodextrins (37) in the mobile phase, as well as the silica bonded cyclodextrins (38-40) as stationary phase have attained spectacular success. A series of rapid, elegant separations have been published. The field of application of this method seems to be inexhaustible. 

Cyclodextrins as Mobile-Phase Components for Separation of Isomers by Reversed-Phase High-Performance Liquid Chromatography... 

The use of cyclodextrins as the mobile phase components which impart stereoselectivity to reversed phase high performance liquid chromatography (RP-HPLC) systems are surveyed. The exemplary separations of structural and geometrical isomers are presented as well as the resolution of some enantiomeric compounds. A simplified scheme of the separation process occurring in RP-HPLC system modified by cyclodextrin is discussed and equations which relate the capacity factors of solutes to cyclodextrin concentration are given. The results are considered in the light of two phenomena influencing separation processes adsorption of inclusion complexes on stationary phase and complexation of solutes in the bulk mobile phase solution. 

Debowski, J. Sybilska, D. Jurcyak, J. 8-Cyclodextrin as a chiral component of the mobile phase for separation of mandehc acid enantiomers in reversed phase systems of high performance liquid chromatography. J. Chromatogr. 1982, 237 (3), 303-306. 

Micelles and cyclodextrins are the most common reagents used for this technique. Micellar electrokinetic capillary chromatography (MECC or MEKC) is generally used for the separation of small molecules [6], Sodium dodecyl sulfate at concentrations from 20 to 150 mM in conjunction with 20 mM borate buffer (pH 9.3) or phosphate buffer (pH 7.0) represent the most common operating conditions. The mechanism of separation is related to reversed-phase liquid chromatography, at least for neutral solutes. Organic solvents such as 5-20% methanol or acetonitrile are useful to modify selectivity when there is too much retention in the system. Alternative surfactants such as bile salts (sodium cholate), cationic surfactants (cetyltrimethy-lammonium bromide), nonionic surfactants (poly-oxyethylene-23-lauryl ether), and alkyl glucosides can be used as well. 

F. BressoUe, M. Audran, T.-N. Pham, and J-J. Vallon, Cyclodextrins and enantiomeric separations of drugs by liquid chromatography and capillary electrophoresis Basic principles and new developments, J. Chro-matogr. B 657 303 (1996). 

---