CHIRAL SEPARATION OF BASIC DRUGS USING CYCLODEXTRIN-MODIFIED CAPILLARY ZONE ELECTROPHORESIS

Capillary zone electrophoresis (CZE) was successfully applied to the chiral separation of basic drugs after addition of a suitable cyclodextrin chiral selector to the electrophoresis buffer. Commercially available cyclodextrins (alpha-, beta-, and gamma-cyclodextrin and heptakis(2,6-di-O-methyl)-beta-cyclodextrin) were evaluated for their enantioselectivity toward 10 compounds having rather complex molecular structures. In contrast to liquid chromatographic attempts, the enantiomers of all racemates investigated could be resolved with a resolution of more than 1.4, except for one (R(S) 1.1), and showed theoretical plate numbers up to 265,000 with good peak shapes. Apart from well-known parameters such as the concentration of the chiral selector added, the resolution was found to depend strongly on the applied field strength. It is shown and explained that the impact of the field strength on the electrophoretic mobilities and the coefficient of electroosmotic flow, and thus on the resolution, cannot be ignored, particularly at enantioseparations of cationic compounds. Quantitative aspects of chiral separations were studied, showing that less than 0.5% of an isomeric impurity, relative to the main optical isomer, can be determined while maintaining good accuracy, acceptable resolution, and good precision. The feasibility of increased sample throughput by injection of next samples while previous separation(s) are still in progress is demonstrated. The results obtained clearly show the potential of cyclodextrin-modified CZE toward quality control of enantioselective syntheses, enantiopurification schemes, and pharmaceutical formulations.