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Water-Oil Partition Profiling of Ionized Drug Molecules Using Cyclic Voltammetry and a 96-Well Microfilter Plate System

Ulmeanu, Sorina ; Jensen, Henrik ; Bouchard, Géraldine ; Carrupt, Pierre-Alain ; Girault, Hubert

In: Pharmaceutical Research, 2003, vol. 20, no. 8, p. 1317-1322

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    Titel
    • Water-Oil Partition Profiling of Ionized Drug Molecules Using Cyclic Voltammetry and a 96-Well Microfilter Plate System
    Autor
    • Ulmeanu, Sorina. Laboratoire d'Electrochimie Physique et Analytique, Ecole Polytechnique Fédérale de Lausanne, CH-1015, Lausanne, Switzerland
    • Jensen, Henrik. Laboratoire d'Electrochimie Physique et Analytique, Ecole Polytechnique Fédérale de Lausanne, CH-1015, Lausanne, Switzerland
    • Bouchard, Géraldine. Institut de Chimie Thérapeutique, Université de Lausanne, CH-1015, Lausanne, Switzerland
    • Carrupt, Pierre-Alain. Institut de Chimie Thérapeutique, Université de Lausanne, CH-1015, Lausanne, Switzerland
    • Girault, Hubert. Laboratoire d'Electrochimie Physique et Analytique, Ecole Polytechnique Fédérale de Lausanne, CH-1015, Lausanne, Switzerland
    Dokumententyp
    • Postprint
    Sprache
    • Englisch
    Veröffentlicht in
    • Pharmaceutical Research, 2003, vol. 20, no. 8, p. 1317-1322. Kluwer Academic Publishers-Plenum Publishers
    Andere elektronische Ausgabe
    OAI-PMH-ID
    • oai:doc.rero.ch:321816
    Summary
    Purpose. A new experimental set-up for studying partitioning of ionizable drugs at the interface between two immiscible electrolyte solutions (ITIES) by amperometry is presented. The method is quite general, as it can be applied to any charged drug molecule. Methods. The procedure is based on 96-well microfilter plates with microporous filters to support 96 organic liquid membranes. The new methodology is first validated using a series of tetra-alkylammonium ions and subsequently used to construct the ion partition diagrams of 3,5-N,N-tetramethylaniline and 2,4-dinitrophenol. The lipophilicity of these drugs was examined by potentiometry and cyclic voltammetry in the NPOE/water system. Results. Cyclic voltammetry resulted in potential-pH profiles of the studied drugs. When the aqueous phase pK a is already known, the logP NPOEof lipophilic drugs could be determined using a very little amount of solvents and drugs. The values of the partition coefficients for the neutral forms agree well with those obtained by potentiometry. Conclusions. The procedure based on commercially available 96-well microfilter plates is shown to be useful for determining logP of ionized drugs in a rapid and efficient way