Journal
INTERNATIONAL JOURNAL OF MASS SPECTROMETRY
Volume 444, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.ijms.2019.06.008
Keywords
SFC-MS/MS; Chiral inversion; Enantioselective bioanalysis; Chiral bioanalysis; Chiral stationary phase; Enantiomer; Supercritical fluid chromatography
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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. (C) 2019 Elsevier B.V. All rights reserved.
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