Contribution to the standardization of the chromatographic conditions for the lipophilicity assessment of neutral and basic drugs

The chromatographic conditions aiming to a better simulation of n-octanol–water partitioning using a base deactivated silica (BDS) column as stationary phase were investigated for structurally diverse basic and neutral drugs. Extrapolated retention factors log kw, determined using different methanol fractions as organic modifier, were considered as lipophilicity indices. The effect of n-decylamine and n-octanol as mobile phase additives was examined and the appropriateness of the final retention outcome to reproduce lipophilicity data was evaluated. Moreover, the influence of n-octanol on the linearity of the log k/methanol fraction relationship and on the uniformity of the retention mechanism was investigated. 1:1 correlation between log kw values and the logarithm of the distribution coefficient (log D) was established for basic drugs in presence of both n-decylamine and n-octanol as mobile phase additives. However, for neutral drugs n-decylamine proved to be a sufficient and more important factor than n-octanol.