title: Novel Instrument for Automated pK(a) Determination by Internal Standard Capillary Electrophoresis.
abstract: The internal standard capillary electrophoresis method (IS-CE) has been implemented in a novel sequential injection-capillary electrophoresis instrument for the high-throughput determination of acidity constants (pK(a)) regardless of aqueous solubility, number of pK(a) values, or structure. This instrument comprises a buffer creation system that automatically mixes within a few seconds four reagents for in situ creation of the separation electrolyte with a pH range of 2-13, ionic strength of 10-100 mM and organic solvent content from 0% to 40%. Combined with 1.2 kV/cm and a short effective length (15 cm to the UV detector) fast 20 s electrophoretic separations can be obtained. The low standard deviation of the replicates and the low variation compared to reference values show that this system can accurately determine acidity constants of drugs by IS-CE. A single pK(a) can be determined in 2 min and a set of 20 measurements in half an hour, allowing rapid, simple, and flexible determination of pK(a) values of pharmaceutical targets.
authors.affiliation: †Departament de Química Analítica and Institut de Biomedicina (IBUB), Universitat de Barcelona, Martí i Franquès 1-11, E-08028 Barcelona, Spain.|‡Australian Centre for Research on Separation Science, School of Chemistry, Faculty of Science, Engineering and Technology, University of Tasmania, Private Bag 75, Hobart, Tasmania 7001, Australia.
authors.forename: Joan M
authors.initials: JM
authors.lastname: Cabot
authors.affiliation: †Departament de Química Analítica and Institut de Biomedicina (IBUB), Universitat de Barcelona, Martí i Franquès 1-11, E-08028 Barcelona, Spain.
authors.forename: Elisabet
authors.initials: E
authors.lastname: Fuguet
authors.affiliation: †Departament de Química Analítica and Institut de Biomedicina (IBUB), Universitat de Barcelona, Martí i Franquès 1-11, E-08028 Barcelona, Spain.
authors.forename: Martí
authors.initials: M
authors.lastname: Rosés
authors.affiliation: ‡Australian Centre for Research on Separation Science, School of Chemistry, Faculty of Science, Engineering and Technology, University of Tasmania, Private Bag 75, Hobart, Tasmania 7001, Australia.
authors.forename: Petr
authors.initials: P
authors.lastname: Smejkal
authors.affiliation: ‡Australian Centre for Research on Separation Science, School of Chemistry, Faculty of Science, Engineering and Technology, University of Tasmania, Private Bag 75, Hobart, Tasmania 7001, Australia.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Breadmore
mesh_terms: D001331:Automation; D019075:Electrophoresis, Capillary / Q000295:instrumentation*; D006863:Hydrogen-Ion Concentration; D000432:Methanol / Q000737:chemistry; D014867:Water / Q000737:chemistry
chemical_list: D014867:Water; D000432:Methanol