Reversed-phase high-performance liquid chromatography for evaluating the lipophilicity of pharmaceutical substances with ionization up to log P(app) = 8

The RP-HPLC determination of drug lipophilicity was evaluated for its potency as a substitute for the determination of log P(Oct-W) values. The relation of log k(w) to log P(app) (= log P(Oct-W) at pH 7.4) is linear for a testset including protonable nitrogen bases. The method is reproducible on different columns (with the same brand and type of the stationary phases) and needs no recalibration then. Three series of substituted benzene homologues (one hydrogen bond acceptor and two weak donor groups) demonstrate structure-retention effects.