Physiologically Relevant Pseudophase High–Performance Liquid–Liquid Chromatography

It is well-established that the lipophilicity of a chemical agent is one of the important determinants of its toxicology, since it determines its partition into physiological fluids or cells and interaction with biologically relevant molecules. Many researchers have proposed approaches to quantify the lipophilicity of chemical agents with the view to measure their bioavailabilities and bioaccumulations, and hence predict aspects of their toxicologies. Lipophilicity has been traditionally quantified on the basis of the logarithm of the partition coefficient of the agent between immiscible lipophilic and hydrophilic solvents (1,2). It is now generally accepted that the logarithm of the partition coefficient between 1-octanol and water is a reasonable model for the prediction of agent transport from a hydrophilic phase into a biophase (3, 4). The selection of 1-octanol as a model for a lipophilic phase has often been questioned but, since there is a large data base for these partition coefficients, there has been little incentive for research into alternative solvent systems. The major criticism of the use of 1-octanol is that it does not include the quasi-fluidic character found in lipoprotein structures in biological systems.