Polysaccharides enantioseparation

J. Dingenen, Polysaccharide phases in enantioseparations in A practical approach to chiral separations by liquid chromatography, G. Subramanian, VCH, Weinheim (1994) Chapter 6. 

Aboul-Enein, H.Y and Ali, I., Optimization strategies for HPLC enantioseparation of racemic drugs using polysaccharides and macrocyclic antibiotic chiral stationary phases, II Farmaco, 57, 513, 2002. 

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. 

Note that not all enantioseparations in SFC are better than in HPLC [34], Bernal et al. [62] described the enantiomeric separation of several pharmaceutical-related compounds on a polysaccharide-based column using HPLC and SFC. They showed that most of the separations obtained by SFC are better, in terms of resolution and analysis time, than the separations obtained by HPLC. However, one compound could not be resolved using SFC, but LC provided baseline resolution. 

Successful enantioseparations using polysaccharide CSPs in combination with pure polar organic mobile phases have been achieved... 

Another practical guide for enantioseparation of pharmaceuticals with the most common types of CSPs has recently been published in a review by Thompson [34]. For polysaccharide and... 

In a comparative study of 102 racemates of pharmaceutical interest with the three techniques, HPLC, CE, and SEC, HPLC was found to have the highest coverage of enantioseparation [64]. The authors state that this probably arose partly as a result of a higher variety of phases being commercially available for HPLC. The phases with the widest application ranges in that study were found to be Chiralpak AD and Chiralcel OD and OJ (i.e., polysaccharide phases). 

The use of polysaccharide-based CSPs instead of protein-based CSPs often increases the peak efficiency and facilifafes faster separafions. Papini ef al. [159] recently developed a method for the enantioseparation of lorazepam and on a Chiralpak OD-R column and an enzymatic hydrolysis was used to determine the amount of the glucoronide metabolite of lorazepam present. The separation was performed in 7 min with an LOQ of 1 and 10 ng/mL for lorazepam in plasma and urine, respectively. Another relatively fast separation for chiral analysis was published by Lausecker and Eischer [188]. They developed a method for determination of the drug candidate R483 within... 

Dingenen J, Polysaccharide phases in enantioseparations, in A Practical Approach to Chiral Separations by Liquid Chromatography (Subramanian G, Ed.), VCH Verlag, Weinheim, Germany, p. 115 (1994). 

Cass et al. [66] used a polysaccharide-based column on multimodal elution for the separation of the enantiomers of omeprazole in human plasma. Amylose tris (3,5-dimethylphenylcarbamate) coated onto APS-Hypersil (5 /im particle size and 120 A pore size) was used under normal, reversed-phase, and polar-organic conditions for the enantioseparation of six racemates of different classes. The chiral stationary phase was not altered when going from one mobile phase to another. All compounds were enantioresolved within the elution modes with excellent selectivity factor. The separation of the enantiomers of omeprazole in human plasma in the polar-organic mode of elution is described. 

Aboul-Enein, H. and Ali, I. (2002) Optimization Strategies for HPLC Enantioseparation of Racemic Drugs Using Polysaccharides and Macrocyclic Glycopeptide Antibiotic Chiral Stationary Phases, Farmaco 57, 513-529. 

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. 

Yashima, E. (2001) Polysaccharide-based chiral stationary phases for high-performance liquid chromatographic enantioseparation, J. Chromatogr. A 906, 105-125. 

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.)...

ENANTIOSEPARATION OF PHARMACELTICALLY RELEVANT CHIRAL COMPOLNUS USING POLYSACCHARIDE TYPE CSPs... 

Other approaches for insolubilization have been proposed by Francotte more stable CSPs could be obtained by cross-linking polysaccharide derivatives photochemical I y initiated ] 163] or thermally initiated ] 164] (Tables 9.5 and 9.6) using a radical reaction. The new CSPs exhibited improved separations for many racemates, predominantly through the ability to use chloroform and other co-solvents. Further, compounds that were insoluble in the commonly used /)-heptane-2-propanol eluents could be easily separated into individual enantiomers, and for many enantioseparations run times can be reduced with chloroform, ethyl acetate or THF containing mobile phases. These improved CSPs are about to be commercialized. 

Another marked disadvantage should be mentioned. As a consequence of the macromolecular nature of the selector, its molar loading on the support material is quite low. Since the number of binding sites per protein molecule is also limited (in contrast to polysaccharide and other polymeric CSPs consisting of the same repetitive sub-selector units), these CSPs have a low loadability [203]. This greatly restricts their use for preparative enantioseparations. 

Enantioseparations in SEC have been reported for several CSPs. including native and derivatized cyclodextrin-based CSPs [427-432. Pirkle-concept CSPs [77,336-338,347,348,363,365,433,434], polysaccharide type CSPs [137.435-438], macrocyclic antibiotic type CSPs [436], and others. 

R590 E. Yashima, Polysaccharide-Based Chiral Stationary Phases for High-Performance Liquid Chromatographic Enantioseparation , J. Chroma-togr.. A, 2001,906,105... 

Chankvetadze, B.,Yamamoto, C., Okamoto,Y. Enantioseparation of selected chiral sulfoxides using polysaccharide-type chiral stationary phases and polar organic, polar aqueous-organic and normal-phase eluents,/. Chromatogr. A,... 

Chankvetadze, B., Kartozia, 1., Yamamoto, C., Okamoto, Y. Comparative enantioseparation of selected chiral drugs on four different polysaccharide-type chiral stationary phases using polar organic mobile phases,/. Pharmaceut. Biomed., 2001, 27, 467-478. 

CyD-based columns for HPLC enantioseparations are well established and several tens of these columns are commercially available at present. Although highly suitable for analytical-scale enantioseparations these columns hardly compete with polysaccharide and macrocydic antibiotic-based CSPs for preparative-scale enantioseparations. More research is needed in this area. 

At present CSPs based on polysaccharide derivatives, chiral ion exchangers, and macrocycUc antibiotics are most commonly used for CEC enantioseparations, but CyD-based CSPs played an important role in establishing of this technique in both open tubular [64, 65] and packed capillary format [65]. 

Krause, K. Girod, M. Chankvetadze, B. Blaschke, G. Enantioseparations in normal- and reversed-phase nano-high-performance liquid chromatography and capillary electrochromatography using polyacrylamide and polysaccharide derivatives as chiral stationary phases. J. Chromatography A 1999, 837 (1-2), 51-63. 

The reversal of enantiomeric elution order for the polysaccharide CSP was first reported by Okamoto et al. in 1991. They found that the reversal of the elution order of the enantiomers on a modified cellulose column was associated with changes in the mobile phase modifiers during the investigation of the direct chromatographic enantioseparation of pyriproxyfen, an insect growth regulator. If one can find such phenomena, although very rare in HPLC, it will be important to understand the reasons for this behavior and to anticipate when such inversions of elution order are likely to occur. 

Okamoto Y, Noguchi J, Yashima E (1998) Enantioseparation on 3,5-dichloro- and 3,5-dimethylphenylcarbamates of polysaccharides as chiral stationary phases for high-performance liquid chromatography. React Funct Polym 37 183-188... 

Lomsadze K, Jibuti G, Farkas T, Chankvetadze B. Comparative high-performance liquid chromatography enantioseparations using polysaccharide based chiral stationary phases prepared by coating of totally porous and core-shell silica particles. J Chromatogr A 2012 1234 50-55. 

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