Abstract
In this chapter, the ability of enantioselective 2D-LC to deal with challenges in chiral separations is discussed. Achiral-chiral multiple heartcut mLC-LC with fast second dimension separations using chiral sub-2 µm totally porous particle or superficially porous particle columns has the potential to be run as a routine quality control method for complex pharmaceuticals with multiple chiral centers and other isomeric structural elements. Also, the value of separations using the reversed column order (i.e., chiral first) and chiral-chiral mLC-LC has been demonstrated. In combination with tandem MS, achiral-chiral mLC-LC can solve the selectivity shortcomings of individual chiral columns and of MS/MS for simultaneous analysis of chiral drug enantiomers and the multiple positional isomers of phase I metabolites frequently observed in enantioselective metabolism studies. A plurality of studies has documented the power of multi-loop achiral-chiral mLC-LC for enantioselective amino acid analysis covering up to all proteinogenic amino acids and isobaric analogs in a single analysis for the determination of amino acid compositions in peptides, and of trace D-amino acids in biomarker studies with biological and food samples. Multi-column 2D-LC platforms are established in the pharmaceutical industry for efficient screening of chiral columns and mobile phase combinations. The chapter also touches enantioselective 2D chromatography by LC-SFC for impurity profiling and by microchip LC-LC for chiral catalyst screening as well as other 2D isomer separations involving chiral columns.
Published Version
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