Accurate determinations of lipophilicity indices benefit from recent advances in chromatographic sciences such as the launch of ultraperformance liquid chromatography (UPLC). The fast strategy presented here emerges as a powerful method suitable for high-throughput log P measurements of therapeutic compounds in isocratic and gradient modes. Because UPLC columns are highly stable in basic pH conditions, this approach allows a direct lipophilicity estimation of basic compounds in their neutral forms.