Immobilized pH gradient gel cell to study the pH dependence of drug lipophilicity.
An experimental setup to study the pH dependence of standard ion-transfer potentials at the water/NPOE interface is presented. The system is composed of a microhole generated by laser photoablation in a 12-microm polyethylene terephthalate film, the aqueous phase consisting of a commercial immobilized pH gradient gel reswelled in electrolyte solution and a droplet of organic solution. Two electrodes are used, an Ag/AgCl aqueous electrode and an Ag/AgTPBCl organic electrode. This setup is applied to the study of two ionizable compounds (pyridine, 2,4-dinitrophenol). Thermodynamic parameters such as the standard transfer potential, the Gibbs energy of transfer, and the partition coefficients of the ionized forms as well as the neutral forms of these drug compounds are evaluated by differential pulse voltammetry. The data obtained are summarized in ionic partition diagrams, which are a useful tool for predicting and interpreting the transfer behavior of ionized drugs at the liquid/liquid interfaces mimicking the biological membranes.
Lam
Hoang-Trang
HT
Laboratoire d'Electrochimie Physique et Analytique, Ecole Polytechnique Fédérale de Lausanne, Station 6, CH-1015 Lausanne, Switzerland.
Pereira
Carlos M
CM
Roussel
Christophe
C
Carrupt
Pierre-Alain
PA
Girault
Hubert H
HH
D019297:2,4-Dinitrophenol / Q000493:pharmacokinetics; D002463:Cell Membrane Permeability; D004563:Electrochemistry; D004566:Electrodes; D005782:Gels; D006863:Hydrogen-Ion Concentration; D007477:Ions; D008564:Membrane Potentials; D008954:Models, Biological; D008956:Models, Chemical; D004364:Pharmaceutical Preparations / Q000737:chemistry; D010599:Pharmacokinetics; D011725:Pyridines / Q000493:pharmacokinetics; D013816:Thermodynamics
D005782:Gels; D007477:Ions; D004364:Pharmaceutical Preparations; D011725:Pyridines; C023666:pyridine; D019297:2,4-Dinitrophenol