ABSTRACT
Many active drugs are racemic 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.
Subject(s)
Cyclodextrins , Stereoisomerism , Chromatography, LiquidABSTRACT
For many drugs, only racemic mixtures are available for clinical use. Because different stereoisomers of drugs often cause different physiological responses, the use of pure isomers could elicit more exact therapeutic effects. Differential complexation of a variety of drug stereoisomers by immobilized beta-cyclodextrin was investigated. Chiral recognition and racemic resolution were observed with a number of compounds from such clinically useful classes as beta-blockers, calcium-channel blockers, sedative hypnotics, antihistamines, anticonvulsants, diuretics, and synthetic opiates. Separation of the diastereomers of the cardioactive and antimalarial cinchona alkaloids and of two antiestrogens was demonstrated as well. Three dimensional projections of beta-cyclodextrin complexes of propanolol, which is resolved by this technique, and warfarin, which is not, are compared. These studies have improved the understanding and application of the chiral interactions of beta-cyclodextrin, and they have demonstrated a means to measure optical purity and to isolate or produce pure enantiomers of drugs. In addition, this highly specific technique could also be used in the pharmacological evaluation of enantiomeric drugs.
