Anal. Chem. 1994,66, 4013-4018
Sulfobutyl Ether ,8-Cyclodextrin as a Chiral Discriminator for Use with Capillary Electrophoresis R. J. Tal$+ D. 0. Thompson,* V. J. Stella, and J. F. Stobaugh' Center for Drug Delivery Research and Department of Pharmaceutical Chemistry, 307 1 Malott Hall, The University of Kansas, Lawrence, Kansas 66045
The first applications of a novel polyanionic derivative of 8-cyclodextrin (8-CD), sulfobutyl ether B-CD (8-CDSBE(IV)), as a stereoisomer selector in capillary electrophoresis are described. Separations were developed for one and two chiral molecules, including (*)-ephedrine, (*)pseudoephedrine, and several structurally related compounds. The separations achieved were found to be superior to those possible with neutral selectors such as 8-CD or heptakis(2,6dimethyl)-B-CD. Base line separationof the four stereoisomers of (&)-ephedrineand (*)-pseudoephedrine was achieved in a single run with 8-CD-SBE(1V). Aspects regarding structural specificity, binding magnitude, and the utility of having a stereoisomer selector with a large countercurrent mobility are discussed. Cyclodextrins (CDs) have recently received considerable attention as chiral discriminators for use in high performance liquid chromatography (HPLC), gas chromatography (GC), and capillary electrophoresis (CE).14 Each of these methodologies has found general utility because of the ease with which the separated enantiomers can subsequently be quantified. CE appears to offer an advantage over HPLC and GC because of the high separation efficiencies and rapid analysis times that can be achieved for aqueous soluble comp~unds.~J Ideally, in a conventionalachiral capillary zone electrophoresis experiment, separations result entirely from differing electrophoretic mobilities for the analytes of interest, with no other separation mechanisms such as surface interactions being involved. Consequently, to achieve a chiral separation, selectivity can be provided by the addition of a chiral discriminator to the running electrolyte. This in turn provides simple control of the separation by alteration of the chiral discriminator concentration. In principle, the success of a given separation is also easier to predict from both the type and the strength of the interaction of the analyte with the chiral discriminator. To date, the two most commonly used cyclodextrins for chiral separations in CE are neutral P-cyclodextrin (p-CD) t Present address: Senior Scientist, Glaxo, Inc., 9 St. Hohn Paiade, Kew 3101, Australia. f Present address: CyDex, L.C., 8675 W. 96th St., Overland Park, KS 66212. ( I ) Hinze, W. L. Sep. Pur$ Methods 1981, 10, 159-237. (2) Berthod, A.; Jin, H. L.; Beesley, T. E.; Duncan, J. D.; Armstrong, D. W. J. Pharm. Biomed. Anal. 1990,8, 123-130. (3) Ward, T. J.; Armstrong, D. W. J. Liq. Chromafogr. 1986, 9, 4 0 7 4 2 3 . (4) Konig, W. A.; Ichein, D.; Runge, T.; Pforr, I.; Krebs, A. J. High Res. Chromatogr. 1990, 13, 702-707. ( 5 ) Szepsi, G.; Gazdag, M. J. Pharm. Biomed. Anal. 1988,6, 623-639. ( 6 ) Kuhn, R.; Hoffstetter-Kuhn, S. Chromatographia 1992, 34, 505-512. (7) Jorgenson, J. W.; Lukacs, K. D. Science 1983, 222, 266-272. (8) Lauer, H. H.; Ooms, J. B. Anal. Chim. Acta 1991, 250, 45-60.
0003-2700/94/0366-40 13$04.50/0 0 1994 Amerlcan Chemical Society
and heptakis(2,6-dimethyl)-~-cyclodextrin(DM-P-CD).9-12 Cyclodextrinshave been utilized in both surface bound forms2" and as mobile phase additives in HPLC.13-16 However, due to the limited surface area to running electrolyte volume ratio, cyclodextrins are predominantly used as running electrolyte adjuvants in CE. Because of their charge neutrality, both p-CD and DM-@-CDhave a limited time frame in which to achieve a separation (Figure 1). The relatively low solubility of p-CD further limits its usefulness (
