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).
Donovan
Stephen F
SF
BASF, Princeton, NJ 08543-0400, USA. stephendonovan@earthlink.net
Pescatore
Mark C
MC
D002851:Chromatography, High Pressure Liquid / Q000295:instrumentation / Q000379:methods*; D000442:Octanols / Q000737:chemistry*; D011142:Polyvinyl Alcohol / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet; D014867:Water / Q000737:chemistry*
D000442:Octanols; C468554:octadecyl-poly(vinyl alcohol); D014867:Water; D011142:Polyvinyl Alcohol