Chiral chromatographic methods

Integration of the peaks for the two diastereomers accurately quantifies the relative amounts of each enantiomer within the mixture. Such diastereometic derivatives may also be analy2ed by more accurate methods such as gc or hplc. One drawback to diastereometic detivatization is that it requites at least 15 mg of material, which is likely to be material painstakingly synthesized, isolated, and purified. The use of analytical chiral chromatographic methods allows for the direct quantification of enantiomeric purity, is highly accurate to above 99.8% ee, and requites less than one milligram of material. 

Despite the difficulties caused by the rapidly expanding literature, the use of chiral stationary phases (CSPs) as the method of choice for analysis or preparation of enantiomers is today well established and has become almost routine. It results from the development of chiral chromatographic methods that more than 1000 chiral stationary phases exemplified by several thousands of enantiomer separations have been described for high-performance liquid chromatography (HPLC). 

Based on preliminary results from Helfferich130, further developments by Davankov and co-workers5 131 133 turned the principle of chelation into a powerful chiral chromatographic method by the introduction of chiral-complex-forming synlhetie resins. The technique is based on the reversible chelate complex formation of the chiral selector and the selectand (analyte) molecules with transient metal cations. The technical term is chiral ligand exchange chromatography (CLEC) reliable and complete LC separation of enantiomers of free a-amino acids and other classes of chiral compounds was made as early as 1968 131. 

For obvious reasons, a very limited number of CSPs was examined, and although this selection is somewhat individual, an attempt has been made to cite key publications and secondary literature. This is still a relatively new field and active research and development is performed worldwide by numerous researchers and commercial companies this makes it a challenging and stimulating area in which to work. However, it must be confessed, that to date probably more than 90% of all chiral compounds are resolvable by one or other existing chiral chromatographic method. Mostly, it is just a matter of taste, experience and availability of equipment and resources as to which method is preferred. 

Meng M, Rohde L, Capka V et al (2010) Fast chiral chromatographic method development and validation for the quantitation of eszopiclone in human plasma using LC/MS/MS. J Pharma... 

Srinivas, N. R. Evaluation of experimental strategies for the development of chiral chromatographic methods based on diastereomer formation. Biomed. Chromatogr., 2004,18, 207-233. 

The absolute configuration of monosaccharides in saccharide chain and the substituted groups of triterpenoid sapogenins is difficult to determine. Chemical analyses combined with chiral chromatographic method have been used to ascertain... 

Historically, the most common technique used to detect chirality and to distinguish enantiomers has been to determine whether a sample rotates plane polarized light. Optical activity and other chiroptical properties that can be measured using ORD and CD (see below) have long been essential for characterizing enantiomers. Their importance has lessened somewhat with the development of powerful NMR methods and chiral chromatographic methods, but their historical importance justifies a brief discussion of the methodology. 

CHIRAL CHROMATOGRAPHIC METHODS IN THE ANALYSIS AND PURIFICATION OF ENANTIOMERS... 

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