Cyclodextrins as mobile

V Seidel, E Poglits, K Schiller, W Lindner. Simultaneous determination of ochratoxin A and zearalenone in maize by reversed-phase high-performance liquid chromatography with fluorescence detection and/8-cyclodextrin as mobile phase additive. J Chrom 635 227-235,1993. 

The chiral resolution using cyclodextrins as mobile phase additives is also controlled by a number of chromatographic parameters as in case of CSPs. The chiral resolution occurred by the formation of diastereoisomeric inclusion complex formation and, hence, the composition of the mobile phase, pH, concentration of cyclodextrins, and temperature are the most important controlling parameters. 

Cyclodextrins as Mobile-Phase Components for Separation of Isomers by Reversed-Phase High-Performance Liquid Chromatography... 

I. Clarot, D. Cledat, S. Battu, and P. J. P. Cardot, Chromatographic study of terpene derivatives on porous graphitic carbon stationary phase with P-cyclodextrin as mobile phase modifier, J. Chromatogr. A 903 (2000), 67. 

Spencer, B.J. Purdy, W.C. High-performance liquid chromatographic separation of equilin, estrone, and estrone derivatives with cyclodextrins as mobile phase additives. J.Liq.Chromatogr., 1995, 18, 4063-4080... 

Numerous chromatographic studies have also been carried out to investigate possible applications of CyDs as multifunctional drug carriers, discussed in more detail in Chapters 14 and 15. For example the retention of psoralen derivatives was investigated on a C-18 column with HP-) -cyclodextrin as mobile phase additive [62]. Assuming 1 1 stoichiometry, in a 52 48 (v/v) methanol water mixture and temperature —5 °C, the corresponding stability constants were 30, 75, and 40 for the complexes of 8-methoxypsoralen, 5-methoxypsoralen and trimethylpsoralen with HP-yS-CyD, respectively. 

Chen, D, S Jiang, Y Chen and Y Hu (2004). HPLC determination of sertraline in bulk drug, tablets and capsules using hydroxypropyl- 8-cyclodextrin as mobile phase additive. Journal of Pharmaceutical and Biomedical Analysis, 34,239-245. 

The overwhelming majority of chiral separations up to now have been carried out by adding various chiral selectors to the mobile phase rather than by using a chiral plate. For example, enantiomers of amino acids were separated by using alpha- and beta-cyclodextrins as mobile phase additives with bonded Cig and cellulose layers (Cserhati and Forgacs, 1996). 

Lambroussi, V., Piperaki, S. and Tsantili-KakouHdou, A., Formation of inclusion complexes between cyclodextrins as mobile phase additives in RP-TLC, and fluoxetine, norfluoxetine, and promethazine, J. Planar Chromatogr, 12 124,... 

Cyclodextrins as chemically banded layers [102] or mobile phase additives [103-105] have been used successfully to resolve a wide variety of alkaloids, steroids and dansyl- and naphthylamide-amino acid derivatives. The low solubility in aqueous solution and f high cost of cyclodextrins restricted the use of these additives > initially. These limitations were overcome by the availability of ... 

A Shibukawa, DK Lloyd, IW Wainer. Simultaneous chiral separation of leu-covorin and its major metabolite 5-methyltetrahydrofolate by capillary electrophoresis using cyclodextrins as chiral selectors. Estimation of the formation constant and mobility of the solute—cyclodextrin complex. Chromatographia 35 419-429, 1993. 

K Shimada, K Hirakata. Retention behavior of derivatized amino acids and dipeptides in high-performance liquid chromatography using cyclodextrin as a mobile phase additive. J Liq Chromatogr 15 1763-1771, 1992. 

Because the steric effect contributes to the complex formation between guest and host, the chiral resolution on these CSPs is affected by the structures of the analytes. Amino acids, amino alcohols, and derivatives of amines are the best classes for studying the effect of analyte structures on the chiral resolution. The effect of analyte structures on the chiral resolution may be obtained from the work of Hyun et al. [47,48]. The authors studied the chiral resolution of amino alcohols, amides, amino esters, and amino carbonyls. The effects of the substituents on the chiral resolution of some racemic compounds are shown in Table 6. A perusal of this table indicates the dominant effect of steric interactions on chiral resolution. Furthermore, an improved resolution of the racemic compounds, having phenyl moieties as the substituents, may be observed from this Table 6. ft may be the result of the presence of n—n interactions between the CCE and racemates. Generally, the resolution decreases with the addition of bulky groups, which may be caused by the steric effects. In addition, some anions have been used as the mobile phase additives for the improvement of the chiral resolution of amino acids [76]. Recently, Machida et al. [69] reported the use of some mobile phase additives for the improvement of chiral resolution. They observed an improvement in the chiral resolution of some hydrophobic amino compound using cyclodextrins and cations as mobile phase additives. 

TABLE 1 Chiral Resolution of Some Racemic Compounds Using Cyclodextrins as the Mobile Phase Additives... 

In addition to high-performance liquid chromatography (HPLC), the chiral resolution using CMPAs was also carried out by supercritical fluid chromatography (SFC) [91] and capillary electrochromatography (CEC) [92-98]. Salvador et al. [91] used dimethylated /1-cyclodextrin as the mobile phase additive on porous graphite carbon as the solid phase for the chiral resolution of tofizopam, warfarin, a benzoxazine derivative, lorazepam, flurbiprofen, temazepam, chlorthalidone, and methyl phehydantoin by SFC. The authors also studied the effect of the concentration of dimethylated /1-cyclodextrin, the concentration of the mobile phase, the nature of polar modifiers, outlet pressure, and the column temperature on the chiral resolution. 

Wang and Porter [92] resolved the enantiomers of oxazepam, lorazepam, and temazepam using /1-cyclodextrin as the CMPA by CEC. The authors varied separation parameters such as voltage and mobile phase. Wei et al. [93] resolved the enantiomers of phenylephrine and synephrine by varying the concentration of /1-cyclodextrin (CMPA), pH, electrolyte concentration, and temperature. Lelievre et al. [99] separated the enantiomers of chlorthalidone using hydroxypropyl /1-cyclodextrin as the CMPA. Lammerhofer and Lindner [90] resolved the enantiomers of N-derivatized amino acids (e.g., 3,5-dinitrobenzoyl, 3,5-dinitro-benzyloxycarbonyl, 2,4-dinitrophenyl, and 9-fluorenylmethoxycarbonyl amino... 

FIGURE 12 Effect of pH on the chiral resolution of HV-ami noglutethimide hy TLC using water and acetonitrile mixture as the mobile phase containing hydroxy trimethylpropyl ammonium-/j-cyclodextrin as the CMPA (from Ref. 103). 

K. Shimada, K. Mitamura, M. Morita, and K. Hirahata, Separation of the diastereomers of baclofen by HPLC using cyclodextrin as a mobile phase additive, J. Liquid Chromatogr., 76 3311 (1993). 

In CE a successful method for enantiomer separation is the addition of a chiral selector to the mobile phase. This practice can be transferred to p-CEC by using a packing bed which consists of bare silica or ODS (octadecylsilica) and a mobile phase containing a chiral additive. At the first time, Lelievre et al. added hydroxypropyl-[5-cyclodextrin to the mobile phase using an ODS packed capillary. The enantiomer separation of chlorthalidone with a resolution Rs of 1.4 was feasible [41]. Deng et al. [59] used an ODS-packed column and (3-cyclodextrin as a mobile phase additive. A theoretical model for the enantiomer separation of salsolinol was developed and compared with the experimental data. For pressure supported CEC, very high pressure (about 100 bar) was applied to the inlet vial so that the mobile phase was mainly driven by the applied pressure. 

Enantiometric mixtures of nimodipine were separated on (3-cyclodextrin-bonded silica gel plates. The plates were developed with light petroleum/ ethyl acetate/methanol, methanol/1% triethylammonium acetate (pH 4.1), or methanol/acetonitrile/1% triethylammonium acetate as mobile phases. Spots were identified by illumination at 365 nm, or by exposure to iodine vapor [11]. 

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