title: Rapid pKa estimation using vacuum-assisted multiplexed capillary electrophoresis (VAMCE) with ultraviolet detection.
abstract: A rapid approach for estimating the pK(a) value of small organic molecules was developed using vacuum-assisted multiplexed capillary electrophoresis (VAMCE) with ultraviolet detection. The VAMCE method employed a 96-capillary array, arranged in a standard 8 x 12 microtiter plate configuration, with each row of capillaries filled with 12 individual running buffers of equal ionic strength (I = 50 mM) covering a pH range from 2.2 to 10.7. A separate compound was injected hydrodynamically into each row of capillaries allowing the estimation of pK(a) values for eight compounds in a single run. The application of a vacuum during the separation generated a bulk fluid flow and allowed the electrophoretic separation to be completed within 5 min. The complete VAMCE method, conditioning, and electrophoretic separation was optimized to allow the pK(a) estimation for between 128 to 168 compounds in an 8-h period. The VAMCE method provided a reliable approach for estimating pK(a) values both within- and between-day. The pK(a) values for a series of 96 compounds estimated by VAMCE agreed well with some of literature pK(a) values with an average absolute difference of 0.22 log units.
authors.affiliation: Department of Chemistry, University of Cincinnati, Cincinnati, Ohio 45221-0172, USA.
authors.forename: Caixia
authors.initials: C
authors.lastname: Zhou
authors.forename: Yingkun
authors.initials: Y
authors.lastname: Jin
authors.forename: Jeremy R
authors.initials: JR
authors.lastname: Kenseth
authors.forename: Mark
authors.initials: M
authors.lastname: Stella
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Wehmeyer
authors.forename: William R
authors.initials: WR
authors.lastname: Heineman
mesh_terms: D019075:Electrophoresis, Capillary / Q000379:methods; D006863:Hydrogen-Ion Concentration; D004364:Pharmaceutical Preparations / Q000032:analysis* / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet / Q000379:methods; D013816:Thermodynamics; D014618:Vacuum
chemical_list: D004364:Pharmaceutical Preparations