Molecular Dynamics of Enantiomeric Separation in HPLC

Chromatographic separation of enantiomers is a dynamic and highly sensitive process governed by complex interactions between the chiral stationary phase, the mobile phase solvent, and the drug molecule. Traditional energy minimization approaches fail to yield a single representative structure that can explain differences in enantiomer residence times. This review explores how explicit-solvent, fully atomistic molecular dynamics (MD) simulations offer a more accurate and mechanistic understanding of chiral recognition in high-performance liquid chromatography (HPLC). By capturing real-time atomic interactions among solvent molecules, drug enantiomers, and chiral selectors, MD simulations provide predictive insights into stereoselective binding, elution order, and separation factors under various conditions. These simulations enhance our ability to design and optimize analytical methods for enantiomeric resolution, offering a valuable tool for pharmaceutical analysis and regulatory compliance.