Lipophilicity assessment of basic drugs (log Po/w determination) by a chromatographic method

A previously reported chromatographic method to determine the 1-octanol/water partition coefficient (log Po/w) of organic compounds is used to estimate the hydrophobicity of bases, mainly commercial drugs with diverse chemical nature and pKa values higher than 9. For that reason, mobile phases buffered at high pH to avoid the ionization of the solutes and three different columns (Phenomenex Gemini NX, Waters XTerra RP-18 and Waters XTerra MS C18) with appropriate alkaline-resistant stationary phases have been used. Non-ionizable substances studied in previous works were also included in the set of compounds to evaluate the consistency of the method. The results showed that all the columns provide good estimations of the log Po/w for most of the compounds included in this study. The Gemini NX column has been selected to calculate log Po/w values of the set of studied drugs, and really good correlations between the determined log Po/w values and those considered as reference were obtained, proving the ability of the procedure for the lipophilicity assessment of bioactive compounds with very different structures and functionalities.