ABSTRACT
Three decades have passed since the first articles by Hansch1,2 were published which started the era of QSPR (quantitative structure-property relationships) and QSAR (quantitative structure-activity relationships) investigations. Numerous parameters were used in these pioneer investigations including lipophilicity that was measured by means of log P, the octanol-water partition coefficient. Lipophilicity is a prime physicochemical descriptor of xenobiotics with relevance to their biological properties. The hydrophobic interaction of drugs with a receptor, the environmental behavior and toxicological properties are examples of a steadily increasing number of topics in which lipophilicity plays an important role. Its usefulness in the assessment of transport properties of drugs through biological membranes, extractions of solutes in aqueous-organic liquid systems, measurement of equilibria, and design of controlled release drug delivery systems is well documented3-6. The numerous articles that have been published have shown, non linear and/or linear relationships of diverse biological activities with log P.7-14. This parameter remains one of the most important in drug design, despite the appearance of books describing new indices. Log P is a widely used parameter in QSAR for quantitative description of lipophilic character of biologically active compounds. A number of empirical and theoretical approaches have been developed during the last twenty years for calculation of log P values.11 The most common methods for determining the equilibria of drugs partitioning between water and n-octanol are measurement of the concentrations at the equilibrium5,12,15-18 calculated from HPLC retention times,19-21 electrochemical determination of partition coefficient,22 and theoretical computation based on the molecular structure of a drug.6,7,23-25 Ford, et al.26 introduced a method for the determination of log P by a novel combination of the micro shake-flask and HPLC techniques. This method is rapid, reliable, and requires only small quantities of the analyte. In this context calculative approaches are superior to experimental procedures.
