Ion mobility-mass spectrometry analysis of diarylquinoline diastereomers: Drugs used for tuberculosis treatment

Abstract

Mycobacterium tuberculosis infection results in more than two million deaths per year and is the leading cause of mortality in people infected with HIV. A new structural class of antimycobacterials, the diarylquinolines, has been synthesized and is being highly effective against both M. tuberculosis and multidrug-resistant tuberculosis. As diarylquinolines are biologically active only under their ( R,S) stereoisomeric form, it is essential to differentiate the stereoisomers ( R,S) and ( R,R). To achieve this, tandem mass spectrometry and ion mobility spectrometry-mass spectrometry have been performed with 10 diarylquinoline diastereomers couples. In this study, we investigated cationization with alkali metal cations and several ion mobility drift gases in order to obtain diastereomer differentiations. We have shown that diastereomers of the diarylquinolines family can be differentiated separately by tandem mass spectrometry and in mixture by ion mobility spectrometry-mass spectrometry. However, although the structure of each diastereomer is close, several behaviors could be observed concerning the cationization and the ion mobility spectrometry separation. The ion mobility spectrometry isomer separation efficiency is not easily predictable; it was however observed for all diastereomeric couples with a significant improvement of separation using alkali adducts compared to protonated molecules. With the use of drift gas with higher polarizability only an improvement of separation was obtained in a few cases. Finally, a good correlation of the experimental collision cross section (relative to three-dimensional structure of ions) and the theoretical collision cross section has been shown.