Polysaccharide-Based Chiral Chromatography Media in HPLC and SFC - Pharmaceutical Technology

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Polysaccharide-Based Chiral Chromatography Media in HPLC and SFC
Polysaccharide-based chiral stationary phases have been developed that comprise chiral selectors immobilized on their support rather than being physically coated. These materials are completely solvent stable, thereby increasing selectivity and and enabling the development of new chiral selectors that have been too unstable in a coated form for general use.

Pharmaceutical Technology

Loading studies, which involve the injection of a range of sample loads to evaluate the isotherms of adsorption of the solutes, demonstrated major differences among the solvents. The adsorption behavior of the α-methyl-α-phenylsuccinimide enantiomers depended considerably on the nature of the mobile phase. In some cases (chloroform and acetonitrile/2-propanol), the separation collapsed rapidly on loading with the second peak merging with the first at relatively low load. In the case of MTBE, the second component peak moved to longer retention time at moderate load and only began to merge with the first eluting component at high loadings. The high loading capacity in this system led to high productivity for the separations, both in HPLC and SMB mode. The productivity of the separations (in kilograms of enantiomer produced per kilogram of CSP per day) is shown in Table III for each of the mobile phases.

Separation in ethyl acetate also had a high loading capacity, which, combined with the high solubility in this solvent, resulted in the highest production rate for both HPLC and SMB. Thus, solubility is only part of the answer for preparative separations. The effect of the solvent on the loading capacity, presumably through its interactions with the stationary phase, is of great importance in preparative separations. This result has been observed only by virtue of the solvent stability of the immobilized polysaccharide-based CSPs.


The new generation of CSPs, based on immobilized polysaccharides, has proven to be versatile in development of enantioselective separation methods, requiring relatively few stationary and mobile phases for success. The range of selectivity of the CSPs is extended by using solvents hitherto forbidden for the older generation of coated polysaccharide stationary phases not only for HPLC separations but also for SFC methods. Furthermore, the nature of the solvents in preparative separations may have a profound influence on both the solubility of the samples and on the loading capacity of the preparative columns. The extended range of solvents now accessible with the availability of immobilized CSPs extends the potential of preparative enantioselective chromatography to new and larger-scale separations.

Geoffrey B. Cox is vice-president of technology at Chiral Technologies, 800 N. Five Points Rd., West Chester, PA 19380, tel. 610.594.2100, fax 610.594.2325,


1. T. Zhang and P. Franco, "Analytical and Preparative Potential of Immobilized Polysaccharide-Derived Chiral Stationary Phases" in Chiral Separation Techniques, G. Subramanian, Ed. (Wiley-VCH, Weinheim, 2007).

2. Y. Okamoto et al., ""Chiral Stationary Phases for HPLC: Cellulose Tris (3,5-dimethyl-phenylcarbamate) and Tris (3,5-dichlorophenylcarbamate) Chemically Bonded to Silica Gel," J. Liq. Chromatogr. 10, 1613 (1987) .

3. L. Oliveros, C. Minguillon, and P. Lopez, "Polysaccharide Derivatives and their use for Preparing Stationary Chiral Phases Suitable for Separating Isomers," French Patent, 2714671 (1994).

4. T. Kubota et al., "Cellulose 3,5-Dimethyl-phenylcarbamate Immobilized onto Silica Gel via Copolymerization with a Vinyl Monomer and Its Chiral Recognition Ability as a Chiral Stationary Phase for HPLC," Chem. Lett. 724 (2001).

5. R. Duval, "Polysaccharides and Oligosaccharides Crosslinked with Bissilane-, Bisthioether-, Bissulphoxyde-, Bissulphone- and Butanediyl-Derivatives and Their Shaping as Substrate Materials," French Patent 2784108 (2000).

6. N. Enomoto et al., "Preparation of Silica Gel-Bonded Amylose through Enzyme-Catalyzed Polymerization and Chiral Recognition Ability of Its Phenylcarbamate Derivative in HPLC," Anal. Chem. 68 2798 (1996).

7. E. Francotte and T. Zhang, "Photochemically Cross-Linked Polysaccharide Derivatives Having No Photopolymerisable Functional Groups," PCT International Patent Application, WO 97/04011 (1997).

8. T. Zhang, D. Nguyen, and P. Franco, "Use of Immobilized Polysaccahride-Based Chiral Stationary Phases in Enantiomeric Separation," presented at Enantiosep '07, Ferrara, April 2007.

9. R.W. Stringham, "Chiral Separation of Amines in Subcritical Fluid Chromatography using Polysaccharide Stationary Phases and Acidic Additives," J Chromatogr. A, 1070, 163 (2005).

10. E Francotte, "Chiral Stationary Phases for Preparative Enantioselective Chromatography" in Preparative Enantioselective Chromatography, G B Cox, Ed. (Blackwell, Oxford, UK, 2005).


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