Chiral separations importance

Chiral separations have become of significant importance because the optical isomer of an active component can be considered an impurity. Optical isomers can have potentially different therapeutic or toxicological activities. The pharmaceutical Hterature is trying to address the issues pertaining to these compounds (155). Frequendy separations can be accompHshed by glc, hplc, or ce. For example, separation of R(+) and 5 (—) pindolol was accompHshed on a reversed-phase ceUulose-based chiral column with duorescence emission (156). The limits of detection were 1.2 ng/mL of R(+) and 4.3 ng/mL of 3 (—) pindolol in semm, and 21 and 76 ng/mL in urine, respectively. 

Enantiomeric separations have become increasingly important, especially in the pharmaceutical and agricultural industries as optical isomers often possess different biological properties. The analysis and preparation of a pure enantiomer usually involves its resolution from the antipode. Among all the chiral separation techniques, HPLC has proven to be the most convenient, reproducible and widely applicable method. Most of the HPLC methods employ a chiral selector as the chiral stationary phase (CSP). 

The importance of steric and hydrogen bond interactions in chiral separations of nonaromatic samples... 

Many times an analyte must be derivatized to improve detection. When this derivatization takes place is incredibly important, especially in regards to chiral separations. Papers cited in this chapter employ both precolumn and postcolumn derivatization. Since postcolumn derivatization takes place after the enantiomeric separation it does not change the way the analyte separates on the chiral stationary phase. This prevents the need for development of a new chiral separation method for the derivatized analyte. A chiral analyte that has been derivatized before the enantiomeric separation may not interact with the chiral stationary phase in the same manner as the underivatized analyte. This change in interactions can cause a decrease or increase in the enantioselectivity. A decrease in enantioselectivity can result when precolumn derivatization modifies the same functional groups that contribute to enantioselectivity. For example, chiral crown ethers can no longer separate amino acids that have a derivatized amine group because the protonated primary amine is... 

Chiral separation of drng molecules and of their precursors, in the case of synthesis of enantiomerically pure drugs, is one of the important application areas of HPLC in pharmaceutical analysis. Besides HPLC, capillary electrophoresis (CE) is another technique of choice for chiral separations. Chapter 18 provides an overview of the different modes (e.g., direct and indirect ones) of obtaining a chiral separation in HPLC and CE. The direct approaches, i.e., those where the compound of interest is not derivatized prior to separation, are discussed in more detail since they are cnrrently the most frequently used techniques. These approaches require the use of the so-called chiral selectors to enable enantioselective recognition and enantiomeric separation. Many different molecnles have been nsed as chiral selectors, both in HPLC and CE. They can be classified into three different groups, based on their... 

Proteins have also been successfully used for chiral separations in CE. One of the characteristics of proteins is their isoprotic point, pi. The protein will mainly be charged positively if pHpI. Therefore, the pH of the BGE is a very important parameter for the optimization of the separations. As with charged-CD derivatives, it is possible to separate both charged and uncharged chiral species with... 

Compared to other chiral separation techniques, the practical importance of CLEC is relatively low because of its complexity. Nevertheless, CLEC is one of the best-investigated techniques from the theoretical point of view. Many theoretical concepts developed in CLEC were of general interest for the explanation and prediction of chiral recognition in all chromatographic systems. 

An extremely important aspect in pharmaceutical research is the determination of drug optical purity. The most frequently applied technique for chiral separations in CZE remains the so-called dynamic mode where resolution of enantiomers is carried out by adding a chiral selector directly into the BGE for in situ formation of diastereomeric derivatives. Various additives, such as cyclodextrins (CD), chiral crown ethers, proteins, antibiotics, bile salts, chiral micelles, and ergot alkaloids, are reported as chiral selectors in the literature, but CDs are by far the selectors most widely used in chiral CE. 

A number of CE/MS applications have been published in the field of chiral separations, mostly using cyclodextrins as chiral selectors. In some cases the partial-filling technique was used (see earlier). The importance of... 

Another method for creating a chiral environment is lo add an optically pure chiral selector to a bulk liquid phase. Chiral additives have several advanlages over chiral stationary phases and continue lo be the predominant mode for chiral separations by tic and capillary electrophoresis (cc). First of all, the chiral selector added to a bulk liquid phase can be readily changed. The use of chiral additives allows chiral separations lo be done using less expensive, conventional stationary phases. A wider variety of chiral selectors are available [ be used as chiral additives than are available as chiral stationary phases, thus, providing the analyst with considerable flexibility. Finally, the use of chiral additives may provide valuable insight into (he chromatographic conditions and/or likelihood ol success with a potential chiral stationary-phase chiral selector. This is particularly important for the development of new chiral stationary phases because of the difficulty and cosl involved. 

Chiral separations have become of significant importance because the optical isomer of an active component can be considered an impurity. Optical isomers can have potentially different dierapeutic or toxicological aclivihes. Tlie pharmaceutical literature is trying to address the issues pertaining to these compounds. Frequently separations can be accomplished by glc, hplc. or cc. 

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