Enantiomeric separation of citalopram base by supercritical fluid chromatography

The chiral separation of citalopram base by supercritical fluid chromatography on a semipreparative Chiralpak AD column was studied with the use of three alcohol‐type modifiers (methanol, ethanol, and 2‐propanol) with different volume percentages (5, 10, and 15%). The best separation was achieved when 10% 2‐propanol was used in the presence of 0.1% diethylamine as additive. Under these conditions, the resolution reached 2.15 and the selectivity was 1.388. In addition, other parameters that affected the retention and separation properties, i.e. temperature, pressure, and density, were studied in detail. At the same pressure, a decrease in the temperature improved the enantioselectivity as the experimental temperature range was below the isoelution temperature. However, the temperature dependence of the retention factor was complicated. As a rule, the retention factor decreased when the temperature increased at the same density. A satisfactory regression of the logarithm of the retention factor versus density and temperature was obtained using a simplified lattice‐fluid model. Surprisingly, the relationship between the Henry constant and density can be accurately correlated by using the same quadratic equation.