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 P-ow) employing a methanol-water gradient and a short octadecyl-poly(vinyl alcohol) (ODP) column is described. This method is different from published HPLC-based loo, P-ow methods because it uses retention times from a rapid methanol-water gradient to directly generate log P-ow estimates. rather than from a series of isocratic mixtures extrapolated to 100% water. These HPLC log P-ow values have good precision and correlate well with traditional shake-flask log P-ow values. If necessary. the log P-ow 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 cam measure the log P-ow 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 h hydrophobicity determinations (we have now carried out thousands of HPLC log P-ow measurements by this method). (C) 2002 Elsevier Science B.V. All rights reserved.