Critical comparison of shake-flask, potentiometric and chromatographic methods for lipophilicity evaluation (log Po/w) of neutral, acidic, basic, amphoteric, and zwitterionic drugs

• Published in: European journal of pharmaceutical sciences Vol. 122; pp. 331 - 340
• Main Authors: Port, Adriana, Bordas, Magda, Enrech, Raquel, Pascual, Rosalia, Rosés, Martí, Ràfols, Clara, Subirats, Xavier, Bosch, Elisabeth
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.09.2018
• Subjects: Concentració dels ions d'hidrogen; Cromatografia de líquids; Drug lipophilicity; Hydrogen-ion concentration; Lipofília; Lipophilicity; Liquid chromatography; log Po/w; log Po/w by liquid chromatography; log Po/w by potentiometry; log Po/w by shake-flask; Potenciòmetres; Potentiometer; log Po/w by shake-flask; Drug lipophilicity; log Po/w by potentiometry; log Po/w; log Po/w by liquid chromatography; log P(o/w) by potentiometry; log P(o/w) by shake-flask; log P(o/w) by liquid chromatography; log P(o/w)
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2018.07.010

In the present study three different procedures have been compared for the determination of the lipophilicity of the unionized species (log Po/w) of neutral, acidic, basic, amphoteric, and zwitterionic drugs. Shake-flask, potentiometric and chromatographic approaches have been assayed in a set of 66 representative compounds in different phases of advanced development. An excellent equivalence has been found between log Po/w values obtained by shake-flask and potentiometry, while the chromatographic approach is less accurate but very convenient for screening purposes when a high-throughput is required. In the case of zwitterionic and amphoteric compounds, either for shake-flask and chromatographic methods, the pH has to be accurately selected in order to ensure the compound to be in its neutral form. [Display omitted]