Water-oil partition profiling of ionized drug molecules using cyclic voltammetry and a 96-well microfilter plate system

Ulmeanu, S. M.; Jensen, Henrik; Bouchard, Géraldine; Carrupt, Pierre-Alain; Girault, H. H.

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Title		Water-oil partition profiling of ionized drug molecules using cyclic voltammetry and a 96-well microfilter plate system
Authors		Ulmeanu, S. M. Jensen, Henrik Bouchard, Géraldine Carrupt, Pierre-Alain Girault, H. H.
Published in		Pharmaceutical Research. 2003, vol. 20, no. 8, p. 1317-1322
Abstract		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 pKa is already known, the logP(NPOE) of 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.
Keywords		Aniline Compounds/chemistry — Electrochemistry/methods — Hydrogen-Ion Concentration — Membranes, Artificial — Phenyl Ethers/chemistry — Quaternary Ammonium Compounds/chemistry — Technology, Pharmaceutical — Tetraethylammonium/chemistry — Water/*chemistry
Identifiers		PMID: 12948031
Full text		Article - Limited access to UNIGE Other version: http://www.springerlink.com/content/g14385701418160j/fulltext.pdf
Citation (ISO format)		ULMEANU, S. M. et al. Water-oil partition profiling of ionized drug molecules using cyclic voltammetry and a 96-well microfilter plate system. In: Pharmaceutical Research, 2003, vol. 20, n° 8, p. 1317-1322. https://archive-ouverte.unige.ch/unige:10668