Lipophilicity of amphoteric and zwitterionic compounds: A comparative study of determination methods

TALANTA

卷:162

Article

Rafols, Clara¹  Rubio, Javier² 

[1] Univ Barcelona, Dept Quim Analit, Marti & Franques 1-11, E-08028 Barcelona, Spain

[2] Masso Analit SA, Montsia 4, El Prat De Llobregat 08820, Spain

关键词: Lipophilicity;    Ampholyte;    Zwitterion;    Shake-flask;    Potentiometry;    Chromatographic Hydrophobicity Index (CHI);   

DOI  :  10.1016/j.talanta.2016.10.038

来源: Elsevier

【 摘 要 】

Common drugs intended for action in plasma (antibacterials, antiallergics, diuretics...) often display both acidic and basic behavior, and some of these amphoteric compounds can appear as zwitterions. In such cases, accurate profiling of lipophilicity vs. pH, which plays a fundamental role in drug pharmacoidnetics, might be complex. In the present work two common lipophilicity determination methods based on the drug distribution between 1-octanol and aqueous buffer i.e. phase equilibration (shake-flask) and two-phase titration (potentiometry), were compared with a high-throughput lipophilicity index, the Chromatographic Hydrophobicity Index (CHI). The results were also compared with log Dow pH-profiles calculated by different algorithms from ACD/Labs. Accurate and similar results were obtained for both octanol-water approaches but, due to the lower determination times and the absence of different ion-pairing buffers, potentiometry was shown to be the most convenient method. CHI vs. pH profiles provide rapid and efficient information, which is very convenient for lipophilicity screening purposes, but may differ slightly from shake-flask and potentiometric results.

【 授权许可】

Free