Octanol/water partitioning simulation by RP ‐ HPLC for structurally diverse acidic drugs: Comparison of three columns in the presence and absence of n ‐octanol as the mobile phase additive

The advantageous effect of n ‐octanol as a mobile phase additive for lipophilicity assessment of structurally diverse acidic drugs both in the neutral and ionized form was explored. Two RP C 18 columns, ABZ + and A quasil, were used for the determination of log k w indices, and the results were compared with those previously reported on a base‐deactivated silica column. At pH 2.5, the use of n ‐octanol‐saturated buffer as the mobile phase aqueous component led to high‐quality 1:1 correlation between log k w and log P for the ABZ + column, while inferior statistics were obtained for A quasil. At physiological pH, the correlations were significantly improved if strongly ionized acidic drugs were treated separately from weakly ionized ones. In the latter case, 1:1 correlations between log D 7.4 and log k w oct indices were obtained in the presence of 0.25% n ‐octanol. Concerning strongly ionized compounds, adequate correlations were established under the same conditions; however, slopes were significantly lower than unity, while large negative intercepts were obtained. According to the absolute difference (diff = log D 7.4 –log k w ) pattern, base‐deactivated silica showed a better performance than ABZ + , however, the latter seems more efficient for the lipophilicity assessment of highly lipophilic acidic compounds. Aquasil may be the column of choice if log D 7.4 <3 with the limitation, however, that very hydrophilic compounds cannot be measured.