Toshihiko Hanai* Pages 52 - 64 ( 13 )
The retention mechanism in reversed-phase liquid chromatography was quantitatively described using log P (octanol-water partition coefficient). The hydrophobic (lipophilic) interaction liquid chromatography was then used to measure the hydrophobicity of a variety of compounds. Furthermore, the technique has been used as an analytical method to determine molecular properties during the drug discovery process. However, log P values cannot be applied to other chromatographic techniques. Therefore, the direct calculation of molecular interactions was proposed to describe the general retention mechanisms in chromatography. The retention mechanisms in reversed-phase liquid chromatography were quantitatively described in silico by using simple model compounds and phases. The competitive interactions between a bonded-phase and a solvent phase clearly demonstrated the retention mechanisms in reversed-phase liquid chromatography. Chromatographic behavior of acidic drugs on a pentyl-, an octyl-, and a hexenyl-phase was quantitatively described in the in silico analysis. Their retention was based on their hydrophobicity, and hydrogen bonding and electrostatic interaction were selectivity of the hexenyl-phase. This review focuses on the quantitative explanation of the retention mechanisms in reversed-phase liquid chromatography and the practical applications in drug discovery.
Acidic drugs, in silico analysis, modeling bonded-phases, quantitative explanation of retention mechanisms, reversed-phase liquid chromatography, solvent effect.
Health Research Foundation, Research Institute for Production Development 4F, 15 Simogamo-morimoto-cho, Sakyoku. Kyoto, 606-0805