Lipophilicity, acid/base character, protein and phospholipid binding can be used in models of in vivo distribution to support lead optimization.
The published HPLC methods for lipophilicity, acid/base character, protein and phospholipid binding are critically reviewed and compared with each other using the solvation equation approach.
Standardization of various methodologies is suggested in order to obtain data suitable for inter-laboratory comparison.
The published models for volume of distribution, unbound volume of distribution and drug efficiency are also discussed. The general relationships between the chemical structure and biomimetic HPLC properties are described in view of ranking and selecting putative drug molecules.