Direct separation of the enantiomers of ramosetron on a chlorinated cellulose-based chiral stationary phase in hydrophilic interaction liquid chromatography mode

Abstract

Ramosetron is an enantiopure active pharmaceutical ingredient marketed in Japan since 1996 and later in a few Southeast Asian countries predominantly as an antiemetic for patients receiving chemotherapy. In this study, a simple and rapid high-performance liquid chromoatography method for the separation of ramosetron and its related enantiomeric impurity by using hydrophilic interaction liquid chromatography mode is presented. Chiral resolution was performed on an analytical column (100 mm × 4.6 mm id) packed with 3 μm particles of cellulose-based Chiralpak IC-3 chiral stationary phase. Using a mobile phase containing acetonitrile-water-diethylamine (100:10:0.1, v/v/v) and setting the column temperature at 35°C, the resolution value was 7.35. At a flow rate of 1 mL/min, the enantioseparation was completed within 5 min. The proposed method was partially validated and it has proven to be sensitive with limit of detection and limit of quantitation of the (S)-enantiomer impurity of 44.5 and 133.6 ng/mL.

Keywords: Chiralpak IC-3; antiemetic drugs; enantiomer separation; hydrophilic interaction liquid chromatography; ramosetron.