DYNAMIC MODIFICATION OF THE CHIRAL BONDING PROPERTIES OF A CHIRAL-AGP COLUMN BY ORGANIC AND INORGANIC ADDITIVES - SEPARATION OF ENANTIOMERS OF ANTIINFLAMMATORY DRUGS

Eight non-steroidal anti-inflammatory agents (NSAIDs) were used as model compounds for studies of organic and inorganic modifier-induced effects on enantioselectivity and retention. Addition of uncharged modifiers such as methanol, ethanol, 1-propanol, 2-propanol and acetonitrile decreases the retention. For some NSAIDs higher enantioselectivity was obtained with than without a modifier in the mobile phase. Tiaprofen could not be resolved using a phosphate buffer without a modifier as the mobile phase. Addition of 1- and 2-propanol to the mobile phase gave separation factors of 1.8 and 1.5, respectively. Modifiers with different hydrogen-bonding properties and hydrophobicity affected the enantioselectivity differently. Three different hydrophobic tertiary amines, N-N-dimethylheptylamine, N-N-dimethyloctylamine and N-N-dimethylnonylamine and N,N-dimethylnonylamine, were used as charged modifiers. Charged organic modifiers have more drastic effects on the enantioselectivity and retention than the uncharged modifiers. It was observed that the NSAIDs could be divided into two groups with respect to their behaviour int he presence of the tertiary amines: carprofen, flurbifrofen, naproxen and tiaprofen belong to group 1 and fenoprofen, ibuprofen, indoprofen and ketoprofen to group 2. The typical behaviour of a group 1 compound is that the retention of the last-eluted enantiomer increases drastically on addition of amine to the mobile phase, whereas the least-retained enantiomer is only affected to a limited extent. The group 2 compounds behave in a different way concerning retention. At amine concentrations greater than or equal to 2.5 mM the retention was lower than that obtained without an amine in the mobile phase. Dramatic improvements in the enantioselectivity for both group 1 and 2 compounds could be obtained by increasing the amine concentration in the mobile phase. Separation factors up to 13 were obtained. It was also possible to affect both the enantioselectivity and the retention by varying the concentration of inorganic cations such as sodium and ammonium ions. The retention of both enantiomers of the NSAIDs increases with increasing concentration of the inorganic ions. A strong improvement of the enantioselectivity was also observed. For example, the enantioselectivity increased from 1.75 to 2.58 for naproxen on increasing the sodium concentration from 0.0148 to 0.16 M. The results obtained with both inorganic cationic additives indicate that ion-pair distribution can be involved in the retention of the anionic solutes.