title: cIEF for rapid pKa determination of small molecules: a proof of concept.
abstract: A capillary isoelectric focusing (cIEF) method was developed for the determination of the ionization constants (pKa) of small molecules. Two approaches used to decrease the electroosmotic flow (EOF) were compared: (i) a hydroxypropylcellulose (HPC) coated capillary in aqueous medium and (ii) the addition of glycerol to act as a viscosifying agent. The cIEF method with the glycerol medium was selected, and the ionization constants of 22 basic and 21 acidic compounds, including 15 pharmaceutical drugs, were determined, resulting in pKa values from 3.5 to 7.4 and 6.4 to 9.3, respectively. cIEF offers an interesting alternative to other techniques for pKa determination with low sample consumption, high throughput and low cost.
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, 30, Quai Ernest-Ansermet, CH-1211 Geneva 4, Switzerland.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Romand
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, 30, Quai Ernest-Ansermet, CH-1211 Geneva 4, Switzerland. Electronic address: julie.shappler@unige.ch.
authors.forename: Julie
authors.initials: J
authors.lastname: Schappler
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, 30, Quai Ernest-Ansermet, CH-1211 Geneva 4, Switzerland.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Veuthey
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, 30, Quai Ernest-Ansermet, CH-1211 Geneva 4, Switzerland.
authors.forename: Pierre-Alain
authors.initials: PA
authors.lastname: Carrupt
authors.affiliation: School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, 30, Quai Ernest-Ansermet, CH-1211 Geneva 4, Switzerland.
authors.forename: Sophie
authors.initials: S
authors.lastname: Martel
mesh_terms: D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D005990:Glycerol / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D007525:Isoelectric Focusing; D008970:Molecular Weight; D054852:Small Molecule Libraries / Q000737:chemistry*
chemical_list: D054852:Small Molecule Libraries; D002482:Cellulose; C008079:hydroxypropylcellulose; D005990:Glycerol
keywords: Capillary isoelectric focusing; Coating; Ionization constant; cIEF