Direct enantiomeric resolution of some cardiovascular agents using synthetic polymers imprinted with (-)-S-timolol as chiral stationary phase by thin layer chromatography.

Molecular imprinted polymers (MIPs) of S-timolol were prepared as chiral stationary phases (CSPs) in thin layer chromatography (TLC). The resolution of the enantiomers of some cardiovascular drugs, including propranolol, atenolol, timolol, nadolol, nifedipine and verapamil were investigated on these CSPs. A mobile phase system of either methanol or acetonitrile was used and the effects of acetic acid content of the mobile phases were also investigated. The best resolution was achieved for enantioseparation of propranolol, timolol and atenolol on plates based on MIP of (-)-S-timolol using methacrylic acid as functional monomer (alpha = 1.52, 1.6, 1.59) respectively, using acetonitrile containing 5% acetic acid and (alpha = 1.47, 1.52, 1.5) in methanol containing 1% acetic acid as mobile phases. The results obtained show that TLC based on MIPs could be applied in the direct separation of several beta-adrenergic drugs. As the side chains on beta-blockers are similar, it is possible that this method could also be used for the resolution of other racemates in this family of drugs. Racemic drugs structurally related to print molecule, were completely resolved into two spots with the MIP plates. In general the retention of (+)-R-isomers was greater than that of (-)-S-isomers, indicating lower stereoselectivity of the MIPs to the dextrorotatory isomers. The method offers a rapid, sensitive and reliable method for quality control for these drugs.

Application of thin-layer chromatography in enantiomeric chiral analysis-an overview.

Several chiral drugs are produced and administered as pure enantiomers, whereas many others, especially of synthetic origin, are used mainly in the form of racemates. The biological and pharmacological activity of chiral compounds depends on their configuration. The racemic drugs may exhibit quite different activity from the optically pure drugs. Often only one of the enantiomers is pharmacologically active and/or even can be toxic. Since numerous enantiomers have been shown to behave differently from at least one point of view, whether pharmacokinetic, pharmacodynamic, toxicological or interaction, there seems to be hardly any exception to the general rule that a racemate cannot be considered as a single drug entity. A variety of chromatographic methods have been developed for optical resolution recently. Usually direct separation of the enantiomers is carried out on HPTLC chiral precoated plates or on plates impregnated with chiral substances. TLC techniques are a developing branch of separation and quantitation of drugs, both in pharmaceutical dosage forms and in biological material. This review presents an overview of the current successful enantioseparations of drugs by TLC and their potential in the analysis of the drug racemates.