Gas phase isomeric differentiation of oleanolic and ursolic acids associated with heptakis-(2,6-di-O-methyl)-beta-cyclodextrin by electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry

Abstract

Oleanolic acid (OA) and ursolic acid (UA) are isomeric triterpenoid compounds with similar pharmaceutical properties. Usually, modern chromatographic and electrophoretic methods are widely utilized to differentiate these two compounds. Compared with mass spectrometric (MS) methods, these modern separation methods are both time- and sample-consuming. Herein, we present a new method for structural differentiation of OA and UA by Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) with the association of heptakis-(2,6-di-O-methyl)-beta-cyclodextrin (DM-beta-CD). Exact MS and tandem MS (MS/MS) data showed that there is no perceptible difference between OA and UA, as well as their beta-cyclodextrin and gamma-cyclodextrin complexes. However, there is a remarkable difference in MS/MS spectra of DM-beta-CD complexes of OA and UA. The peak corresponding to the neutral loss of a formic acid and a water molecule could only be observed in the MS/MS spectrum of the complex of DM-beta-CD : OA. Molecular modeling calculations were also employed to further investigate the structural differences of DM-beta-CD : OA and DM-beta-CD : UA complexes. Therefore, by employing DM-beta-CD as a reference reagent, OA and UA could be differentiated with purely MS method.