Semipreparative enantiomeric separation of omeprazole by supercritical fluid chromatography

Omeprazole, a widely used antiulcer drug, has been enantiomerically separated at semipreparative scale on a polysaccharide based chiral stationary phase by supercritical fluid chromatography (SFC). For this work, a modular supercritical fluid chromatograph was adapted to operate at semipreparative scale and a Chiralpak AD (250 mm × 10 mm) column was used. The effect of two organic modifiers (ethanol and 2-propanol) was studied, and different injection volumes and concentrations of the omeprazole racemic mixture were evaluated in order to obtain high enantiomeric purities and production rates. Better results were achieved using concentration overloading instead of volume overloading. The recoveries decreased when the requirements of enantiomeric purity or the load increased, but it was possible to recover 100% of both enantiomers at an enantiomeric purity higher than 99.9% under some loading conditions, like injecting 1 and 2 ml of a solution of 3 g/l. As far as production rates are concerned, the best result for S-(−)-omeprazole at that purity (27.2 mg/h) was achieved with sample concentrations of 10 g/l and the injection of 2 ml, while a volume of 4 ml was better in the case of R-(+)-omeprazole (20.5 mg/h).