DIRECT LIQUID-CHROMATOGRAPHIC ENANTIOSEPARATION OF SOTALOL AND OTHER BETA-BLOCKERS USING AN ALPHA(1)-ACID GLYCOPROTEIN-BASED CHIRAL STATIONARY-PHASE

The behaviour of an alpha(1)-acid glycoprotein-based chiral stationary phase (Chiral AGP) towards changes in pH and organic modifier in the mobile phase was investigated in order to deduce suitable conditions f or the liquid chromatographic enantioseparation of a series of beta -a drenoreceptor blocking drugs. The effects of the pH of the mobile phas e on retention, selectivity and resolution were studied. Methanol was the only non-ionic modifier tested in the mobile phase while different aliphatic carboxylic acids (C-4 to C-8) and alkanesulfonic acids (C-6 to C-8) were used as ionic modifiers. The influence of the nature and concentration of these modifiers on retention and enantioselectivity was investigated. Under these conditions, enantiomeric separations cou ld be obtained for more than 70% of the beta-blocking agents examined. The use of heptanoic acid as an ionic additive in the mobile phase ha s permitted the resolution of sotalol enantiomers. An enantioselective assay for sotalol was then developed and validated.