Enantioseparation of erythro-mefloquine and its analogues in capillary electrophoresis.

The enantioseparations of the chiral antimalaria drug (R,S)-erythro-alpha-(2-piperidyl)-2,8-bis(trifluoromethyl)4-quinolinemethanol (erythro-mefloquine, erythro-MQ) and its analogues were studied by capillary electrophoresis (CE) using cyclodextrins (CDs) as chiral selectors. The emphasis was put on the enantiomer affinity pattern of MQ towards different CDs as well as on simultaneous enantioseparations of erythro-MQ and its structural analogues. All three native CDs resolved the enantiomers of erythro-MQ and the enantiomer affinity pattern was the same, i.e. (+)-erythro-MQ was the more tightly bond enantiomer. However, the affinity pattern of erythro-MQ enantiomers was opposite in the case of heptakis-(2,3,6-tri-O-methyl)-beta-CD (TM-beta-CD), heptakis-(2,3-di-O-methyl-6-sulfo)-beta-CD (HDMS-beta-CD), heptakis-(3-O-methyl-2,6-di-O-sulfo)-beta-CD (HMdiSu-beta-CD) and randomly sulfated beta-CD (SU-beta-CD). Randomly hydroxyalkylated and acetylated derivatives of CDs appeared to be suitable chiral selectors for simultaneous enantioseparation of erythro-MQ and its analogues.

Comparative enantioseparations with native beta-cyclodextrin, randomly acetylated beta-cyclodextrin and heptakis-(2,3-di-O-acetyl)-beta-cyclodextrin in capillary electrophoresis.

Comparative enantioseparations were performed with three neutral cyclodextrins (CDs) in capillary electrophoresis (CE). In particular, native beta-CD was compared with single component heptakis(2,3-di-O-acetyl)-beta-CD (HDA-beta-CD) and randomly acetylated beta-CD (Ac-beta-CD) with the emphasis on the enantiomer migration order. The opposite affinity of the enantiomers of several chiral analytes was observed towards native beta-CD and its acetylated derivatives. The enantiomer affinity pattern of some chiral analytes was also opposite towards the two acetylated derivatives of beta-CD. In the case of the chiral drug clenbuterol (CL) an attempt was made to evaluate the possible structural reasons of the affinity reversal using one- and two-dimensional as well as transverse rotating frame nuclear Overhauser effect spectroscopy (ROESY). Significant differences were observed between the structure of the CL complexes with beta-CD and HDA-beta-CD.

Comparative enantioseparations with native beta-cyclodextrin and heptakis-(2-O-methyl- 3,6-di-O-sulfo)-beta-cyclodextrin in capillary electrophoresis.

Twenty-three cationic chiral analytes were resolved in capillary electrophoresis using native beta-cyclodextrin and single isomer heptakis-(2-O-methyl-3,6-di-O-sulfo)-beta-cyclodextrin as chiral selectors. For 12 of 16 chiral analytes resolved with both chiral selectors the enantiomer migration order was opposite. In selected cases the structure of cyclodextrin-analyte complexes in aqueous solution was investigated using one-dimensional transverse rotating frame nuclear Overhauser and exchange spectroscopy. It was found that in contrast to mainly inclusion-type complexes between chiral analytes and beta-cyclodextrin, external complexes are formed between the chiral analytes and structurally crowded, highly charged heptakis-(2-O-methyl-3,6-di-O-sulfo)-beta-cyclodextrin.

Enantioseparation of glutethimide and its 5-OH-metabolite in capillary electrophoresis and study of selector-selectand interactions using one-dimensional rotating frame nuclear Overhauser and exchange spectroscopy.

Enantioseparation of glutethimide (GT) and its 5-hydroxy metabolite (5-OH-GT) has been studied with several charged cyclodextrin (CD) derivatives. The emphasis was made on the enantiomer migration order of GT and simultaneous enantioseparation of GT and 5-OH-GT. The possible structural differences of GT complexes with three different single isomer charged CD derivatives were studied using one-dimensional rotating frame nuclear Overhauser and exchange spectroscopy (1-D ROESY).

Enantioseparation of chiral vasodilator drug isoxsuprine in high-performance liquid chromatography and capillary electrophoresis.

Two independent methods using high-performance liquid chromatography (HPLC) on polysaccharide type chiral stationary phase (CSP) and capillary electrophoresis (CE) with native and derivatised cyclodextrins (CD) have been proposed for the enantioseparation of chiral vasodilator drug isoxsuprine (ISP). The methods have been compared from the viewpoint of separation characteristics (efficiency, sensitivity, analysis time, costs, etc.).