Journal zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA of Pharmaceutical & Biomedical Analysis Vol. 8, No. 2, pp. 123-130,199O Printed in Great Britain 0731-7085/90 $3.00 + 0.00 @ 1990 Pergamon Press plc Cyclodextrin chiral stationary phases for liquid chromatographic separations of drug stereoisomers” ALAIN BERTHOD,? HENG LIANG JIN, THOMAS E. BEESLEY, JO DEE DUNCAN and DANIEL W. ARMSTRONGS Department of Chemktty, University of Missouri-Rolla, MO 65401, USA Al&r-act: Many active drugs are tacemic mixtures. Because the two enantiomers of a racemate often cause different pharmacological responses, the use of optically pure isomers is desirable and may be soon required. Cyclodextrin-bonded silica gel can be used as chiral stationary phase (CSP) in liquid chromatography. The enantiomers of 25 different racemic drugs were separated on such CSPs in the reversed-phase mode. The principal features of the cyclodextrin chiral recognition mechanism are recalled and some information on future trends for cyclodextrin CSPs is provided. Keywords: Chiral separation; cyclodextrin; liquid chromatography ; racemic drugs. zyxwvutsrqponmlkjihgfedcbaZYXWVUT Introduction One of the common threads of all living systems is that they are composed of the same types of chiral molecules. All naturally occur- ring amino-acids belong to the L-series. Racemic o-amino-acids have been detected in certain carbonaceous meteorites, indicating that those amino-acids were not produced by living forms. They were more likely produced by random processes. Also, most natural sugars are members of the o-series. Phospho- lipids, steroids, nucleotides, nucleosides, and bile salts are other examples of biological chiral materials. It has been reported that about 57% of the active pharmaceutical compounds prescribed in the United States contain at least one chiral carbon atom [ 1, 21. The biological activity of the two enantiomeric forms of an active drug can be significantly different. It was found that the L-form of thalidomide (N-(2,6-dioxo-3- piperidinyl)phthalimide) is a powerful terato- gen and the D-form is a sedative and soporific drug [3,4]. The administration of the racemate n&-thalidomide to pregnant women was asso- ciated with a large number of newborn ab- normalities. The drug was quickly withdrawn from this market. Another example of enantio- selective biological activity is given by pro- pranolol, the second most commonly pre- scribed drug in the United States. The (S) enantiomer of propranolol is about 100 times as potent as the (R) isomer [l, 51. Such differences in pharmacological activity be- tween enantiomers is often the rule rather than the exception. However, in the period 1983- 1985, 88% of the new chiral drugs introduced were marketed as racemates [2]. It can be predicted that many racemic compounds will soon be considered as drugs with a 50% impurity [l, 2, 41. Stereoisomeric separation is a very import- ant analytical problem. Liquid chromatog- raphy (LC) and more recently gas chromatog- raphy (GC) are the most powerful techniques in enantiomeric separations [6, 71. A chiral stationary phase (CSP) is most often used with a simple achiral mobile phase [6]. Among the available CSPs for LC are the polymeric chiral phases, the crown ether phases, the protein CSPs [8], the rr-complex, hydrogen bond CSPs (Pirkle-type) [9], and the cyclodextrin (CD) bonded CSPs [6]. The latest CSPs were devel- oped and introduced by Armstrong et al. in 1984 [lo, 111. The aim of this work is to present the separation of some drug stereoisomers using CD CSPs and hydroorganic mobile phases. The principal features of the CD chiral recognition mechanism are reiterated and some information on future trends for CD CSPs is provided. *Presented at a symposium at the 40th Pittsburgh Conference and Exposition, Atlanta, Georgia, March 1989. ton leave from Universite de Lyon 1, Laboratoire des Sciences Analytiques, UA CNRS 435, 6%22 Villeurbanne cedex, France. *Author to whom correspondence must be addressed. 123