Stereoselective supercritical fluidic chromatography –mass spectrometry (SFC-MS) as a fast bioanalytical tool to assess chiral inversion in vivo and in vitro

Abstract

The stereoisomers of a chiral drug can exhibit great differences in pharmacodynamic and/or pharmacokinetic properties. Chiral bioanalytical assays are necessary to measure the concentrations of individual enantiomers and/or their chiral metabolites in biological samples in order to assess the absorption, distribution, metabolism, excretion, and toxicity of the individual enantiomers. In addition, chiral assays are required to evaluate potential chiral inversion caused by the biotransformation process. While normal phase or reversed phase chromatography remains the common choices for chiral bioanalytical assays, supercritical fluid chromatography (SFC) demonstrated shorter analysis time without affecting separation efficiency, due to the lower viscosity and faster mass transfer properties of supercritical or subcritical carbon dioxide than traditionally used mobile phases. In this paper, we present examples for developing chiral SFC-multiple reaction monitoring (MRM) assays to measure the pharmacokinetic profiles of stereoisomers of drugs in three distinct cases. Furthermore, these assays can be used to investigate the potential chiral inversion of the small molecule drugs from in vivo or in vitro sources.