Development of an improved ligand exchange chiral stationary phase based on leucinol for the resolution of proton pump inhibitors

Abstract

As an effort to develop improved ligand exchange chiral stationary phases (CSPs) for the resolution of chiral drugs, the residual silanol groups on the silica surface of a CSP based on sodium N-[(S)-1-hydroxymethyl-3-methylbutyl]-N-undecylaminoacetate, a (S)-leucinol derivative, were protected with n-octyl groups. The residual silanol group-protected CSP was applied to the resolution of proton pump inhibitors (PPIs) such as omeprazole, pantoprazole, lansoprazole and rabeprazole. The resolution of PPIs on the residual silanol group-protected CSP was excellent with the separation factors (α) in the range of 4.32-6.42 and the resolution factors (RS) in the range of 6.70-7.15. The improved chiral recognition ability of the residual silanol group-protected CSP was rationalized to be originated from the protection of the non-enantioselective interaction sites on the silica surface and the improved lipophilicity of the stationary phase.

Keywords: Chiral stationary phase; Enantiomer separation; Ligand exchange; Liquid chromatography; Proton pump inhibitors.