Water-oil partition profiling of ionized drug molecules using cyclic voltammetry and a 96-well microfilter plate system.
OBJECTIVE
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.
Ulmeanu
Sorina M
SM
Laboratoire d'Electrochimie Physique et Analytique, Ecole Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland.
Jensen
Henrik
H
Bouchard
Géraldine
G
Carrupt
Pierre-Alain
PA
Girault
Hubert H
HH
D019297:2,4-Dinitrophenol / Q000737:chemistry; D000814:Aniline Compounds / Q000737:chemistry; D004563:Electrochemistry / Q000379:methods; D006863:Hydrogen-Ion Concentration; D008567:Membranes, Artificial; D010647:Phenyl Ethers / Q000737:chemistry*; D000644:Quaternary Ammonium Compounds / Q000737:chemistry*; D013678:Technology, Pharmaceutical; D019789:Tetraethylammonium / Q000737:chemistry; D014867:Water / Q000737:chemistry*
D000814:Aniline Compounds; D008567:Membranes, Artificial; D010647:Phenyl Ethers; D000644:Quaternary Ammonium Compounds; D014867:Water; C052377:tetrapropylammonium; C015165:N,N-dimethyl-3,5-xylidine; D019789:Tetraethylammonium; C027917:tetramethylammonium; D019297:2,4-Dinitrophenol