CHIRAL SEPARATIONS OF BETA-BLOCKING DRUG SUBSTANCES USING DERIVATIZATION WITH CHIRAL REAGENTS AND NORMAL-PHASE HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY

Eighteen beta-blockers currently on sale in Denmark were investigated for the possible separation of the enantiomers by use of normal-phase HPLC following derivatization with three different chiral derivatization agents: (-)-camphanic acid chloride (S)-(-)-1-phenylethyl isocyanate and 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl isothiocyanate. Chromatography was performed using a 5-mum silica column (120 x 4.6 mm I.D.) with mixtures of dichloromethane, n-heptane and methanol as eluents. The results showed that all the beta-blockers available in both enantiomeric forms (seventeen) can be baseline separated by at least one of the three procedures. The purpose of the investigations was an evaluation of the various approaches concerning the possibilities of method standardization.