The Impact of Lipophilicity in Drug Discovery: Rapid Measurements by Means of Reversed-Phase HPLC

Lipophilicity constitutes a vital physicochemical property in drug design as it is connected with pharmacodynamic and pharmacokinetic properties as well as toxicological aspects of candidate drugs. Traditional partitioning experiments to determine n-octanol-water coefficients are laborious and time-consuming, while they cannot be reliably performed for highly lipophilic or compounds undergoing degradation. Alternatively, lipophilicity of candidate drugs can be accurately and reproducibly determined using reversed-phase liquid chromatography. In this chapter, the details of protocols for lipophilicity assessment using reversed-phaseChromatography reversed-phase HPLC, under conditions which provide the best simulation of n-octanol-water partition coefficients, are described.