Method for measuring the logarithm of the octanol–water partition coefficient by using short octadecyl–poly(vinyl alcohol) high-performance liquid chromatography columns

A simple, quick, versatile and inexpensive HPLC method to estimate the logarithm of the octanol–water partition coefficient (log Pow) employing a methanol–water gradient and a short octadecyl–poly(vinyl alcohol) (ODP) column is described. This method is different from published HPLC-based log Pow methods because it uses retention times from a rapid methanol–water gradient to directly generate log Pow estimates, rather than from a series of isocratic mixtures extrapolated to 100% water. These HPLC log Pow values have good precision and correlate well with traditional shake-flask log Pow values. If necessary, the log Pow determination (including replications) can easily be carried out using only a milligram of sample. By suppressing ionization of acids and bases by the use of a buffer in the aqueous phase, the method can measure the log Pow of neutral organic molecules at any pH between 2 and 13. The method can be used with impure material and is rapid, 7 min per run and 4 min equilibration; it lends itself to and has been utilized for high-throughput hydrophobicity determinations (we have now carried out thousands of HPLC log Pow measurements by this method).