Effect of n-octanol in the mobile phase on lipophilicity determination by reversed-phase high-performance liquid chromatography on a modified silica column

In this study, we show that the addition of n-octanol to the mobile phase improves the chromatographic determination of lipophilicity parameters of xenobiotics (neutral solutes, acidic, neutral and basic drugs) on a Phenomenex Gemini C18 column. The Gemini C18 column is a new generation hybrid silica-based column with an extended pH range capability. The wide pH range (2–12) afforded the examination of basic drugs and acidic drugs in their neutral form. Extrapolated retention factor values, log k ′ w ( o ) , obtained on the above column with the n-octanol-modified mobile phase were very well correlated (1:1 correlation) with literature values of log P (logarithm of the partition coefficient in n-octanol/water) of neutral compounds and neutral drugs (69). In addition, we found good linear correlations between measured log k ′ w ( o ) values and calculated values of the logarithm of the distribution coefficient at pH 7.0 (log D7.0) for ionized acidic and basic drugs (r2 = 0.95). The Gemini C18 phase was characterized using the linear solvation energy relationship (LSER) model of Abraham. The LSER system constants for the column were compared to the LSER constants of n-octanol/water extraction system using the Tanaka radar plots. The comparison shows that the two methods are nearly equivalent.