Abstract
Since the enantiomers of a number of racemic drugs have been found to have different activities or modes of action, enantioselective analysis is becoming more important. A number of different approaches to chromatographic chiral resolutions have been evaluated for their ability to resolve the enantiomers of racemic beta blocking drugs, Three chiral HPLC columns were investigated; a cyclodextrin phase, an (R)-3,5-dinitrabezoylphenylglycine phase and a protein phase. The acid glycoprotein phase successfully resolved atenolol, alprenolol, metoprolol, oxprenolol, propranolol and verapamil with 0.01M phosphate buffer eluents modified with either acetonitrile or isopropanol. The (R)-3,5-dinitrobenzoylphenylglycine phase was used with eluents of Isopropanol in hexane and resolutions of propranolol, oxprenolol, metoprolol, alprenolol and pronethalol were achieved after formation of the 1- or 2-naphthamide derivatives, although no separations were achieved for the underivatised samples. The cyclodextrin phase was also found to be unsuccessful in resolving underivatised samples of propranolol and verapamil. However preliminary results indicate that resolutions are possible after the formation of their trifluoroacetyl derivatives. The cyclodextrin phase was also successfully used to resolve the enantiomers of chlorpheniramine and the geometric isomers of clomiphene. In addition to the chiral HPLC stationary phases, a (+)-10-camphorsulphonic acid mobile phase additive was investigated, although this was found to be completely unsuccessful. Finally the use of a chiral diamide GLC column was investigated. This was not suited to the analysis of beta blockers, even after derivatisation, although derivatised amino acids were well resolved. The use of computer modelling to predict the degree of separation of enantlomers was also investigated for the (R)-3,5-dinitrabenzoyl phenylglycine phase, with the interaction energies between the phase and both isomers of each compound calculated for the most stable conformation. From a comparison with the experimental results, it was shown that this approach to prediction was unsuccessful.