Analytical chromatography cyclodextrins

Analytically, the inclusion phenomenon has been used in chromatography both for the separation of ions and molecules, in Hquid and gas phase (1,79,170,171). Peralkylated cyclodextrins enjoy high popularity as the active component of hplc and gc stationary phases efficient in the optical separation of chiral compounds (57,172). Chromatographic isotope separations have also been shown to occur with the help of Werner clathrates and crown complexes (79,173). 

GC using chiral columns coated with derivatized cyclodextrin is the analytical technique most frequently employed for the determination of the enantiomeric ratio of volatile compounds. Food products, as well as flavours and fragrances, are usually very complex matrices, so direct GC analysis of the enantiomeric ratio of certain components is usually difficult. Often, the components of interest are present in trace amounts and problems of peak overlap may occur. The literature reports many examples of the use of multidimensional gas chromatography with a combination of a non-chiral pre-column and a chiral analytical column for this type of analysis. 

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... 

Y Martin-Biosca, C Garcia-Ruiz, ML Marina. Fast enantiomeric separation of uniconazole and diconazole by electrokinetic chromatography using an anionic cyclodextrin. Application to the determination of analyte-selector apparent binding constants for enantiomers. Electrophoresis 21 3240—3248, 2000. 

If pH does not provide adequate separation or if analytes are neutral, use surfactants for micellar electrokinetic capillary chromatography. For chiral solutes, try adding cyclodextrins. 

In contrast, CSPs have achieved great repute in the chiral separation of enantiomers by chromatography and, today, are the tools of the choice of almost all analytical, biochemical, pharmaceutical, and pharmacological institutions and industries. The most important and useful CSPs are available in the form of open and tubular columns. However, some chiral capillaries and thin layer plates are also available for use in capillary electrophoresis and thin-layer chromatography. The chiral columns and capillaries are packed with several chiral selectors such as polysaccharides, cyclodextrins, antibiotics, Pirkle type, ligand exchangers, and crown ethers. 

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). 

Chiral chromatography methods are considered by many to be superior to conventional methods in that, besides analytical applications, they offer the greatest potential for the preparation of optically pure forms of the isomers [5,27,28]. In these examples the third chiral species is an integral part of the LC (or GC) system and may appear as a plain stationary phase (cyclodextrins),... 

In gel inclusion chromatography (GIC), the insoluble, swelling cyclodextrin polymers are utilized (24-26). For routine analytical purposes this method is too slow and time consuming, but some highly effective preparative separations including enantiomeric resolutions have been published. This approach seems to be very promising for semi-micro or laboratory scale preparative separations. 

Figure 8 shows the analytical base-line separation of quebrachamine antipodes by inclusion chromatography on B-cyclodextrin polymers. 

An advantage of cyclodextrins over the common stationary phases is the high selectivity toward the isomeric substances. It has been demonstrated that many positional and geometric isomers can be separated by packed-column GSC in a very short time (i.e. analysis time does not exceed 2 minute) in separation of a mixture of o-, m- and p-isomers. From the analytical viewpoint, the low efficiency of the columns used is a disadvantage. Also, there ar other drawbacks of the gas-solid chromatography using CO s nonlinearity of the separation isotherm over a wider concentration range and poor reproducibility in the preparation of the CD columns utilized. 

On the other hand, capillary gas chromatography with liquid crystals yields very good analytical separations (even for critical pairs of isomers) as the GLC system is used and an inherent lower selectivity compared to cyclodextrins is compensated for by the higher efficiency of the capillary columns Therefore, future work should be directed toward reproducible preparation of capillary columns with cyclodextrins and to other liquid crystals with a higher selectivity ... 

Cyclodextrins were used for the modification of such chromatographic techniques as gas chromatography, classical liquid chromatography, high performance liquid chromatography, thin layer chromatography and many hyphenated techniques. Since in the study of enantiomeric composition of monoterpenes gas chromatography modified with cyclodextrins is the main analytical tool, this method will be more widely discussed later on. 

As shown in Eq. (2) together with the chiral recognition Kk + Kg), the other necessary requirement for enantioseparations in CE is a mobility difference between the free and the complexed analyte fXf - fjL, 0). Otherwise, it will be impossible to transfer a chiral recognition into a chiral separation. This requirement does not hold when neutral analytes are analyzed with neutral chiral selectors. In such a case, an additional buffer component is required that will assist in generating a difference between the mobilities of an analyte in its free and complexed forms with a chiral selector. This is achieved by an achiral micellar phase in cyclodextrin-modified micellar electrokinetic chromatography (CD-MEKC) [9]. However, a charged CD or a chiral micellar phase can combine the... 

Chiral columns are used routinely for the analytical separation of optical isomers.20 Typical columns use tribenzoates, or tris(phenyl carbamates), of cellulose or amylose as well as cyclodextrins. Flash chiral chromatography has... 

Juvancz Z, Szejtli J. 2002. The role of cyclodextrins in chiral selective chromatography. Trends in Analytical Chemistry 21(5) 379-388. 

A considerable number of CE separation methods exist for a wide variety of analytes. However, nitrosamines separation and determination by CE requires additional development for its practical use. " " For the separation of hydrophilic, low molecular weight, neutral, and polar compounds such as nitrosamines, it is necessary to develop CE techniques for enhancing the selectivity. The main reason is that these compounds do not interact strongly with the commonly used surfactants (e.g., sodium dodecyl sulfate, SDS) or other buffer modifiers such as cyclodextrins in electrokinetic chromatography. The separation depends on several factors which must be optimized to reach... 

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