title: Precision evaluation of chiral capillary electrophoretic methods in the context of inter-instrumental transfer: constant current versus constant voltage application.
abstract: Capillary electrophoresis (CE) is an electrophoretic separation technique that was rapidly increasing in popularity some years ago and that led to high expectations. Because of their different separation mechanisms, CE and HPLC are alternative and complementary separation techniques. Chiral molecules can be directly separated with CE by simply adding a chiral selector to the running buffer solution, leading to flexible and cheap methods. Major drawbacks of capillary electrophoretic separation methods are, however, the lower precision compared to HLPC methods and a more problematic analytical method transfer. Both above stated disadvantages limit the generalized use of CE methods in the pharmaceutical industry. Multiple solutions have been suggested to improve the precision of CE methods. In this work the application of a constant current during the electrophoretic separation instead of the more commonly used application of a constant voltage was studied on two CE instruments with different cooling mechanisms. This was done in the context of optimizing method transfer conditions. A constant current may reduce the generation of heat in the capillary and the consequentially radial and axial temperature fluctuations that both negatively influence the precision of the peak areas, migration times and resolutions of a CE method. The repeatability and time-different intermediate precision of both electrophoretic separation modes were compared on two different CE instruments after a successful analytical method transfer. The chiral separations of three beta-blockers, propranolol, sotalol and betaxolol, were used as test cases. A constant current led to a general improvement of the repeatability and time-different intermediate precision of the relative Area Under the Curve of all three beta-blockers, while that of the migration times remained rather constant. It also led to more similar electropherograms than the application of a constant voltage.
authors.affiliation: Department of Analytical Chemistry and Pharmaceutical Technology, Center for Pharmaceutical Research, Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090 Brussels, Belgium.
authors.forename: Bart
authors.initials: B
authors.lastname: De Cock
authors.affiliation: Department of Analytical Chemistry and Pharmaceutical Technology, Center for Pharmaceutical Research, Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090 Brussels, Belgium; Laboratory of Instrumental Analysis and Bioelectrochemistry, Institute of Pharmacy, Université Libre de Bruxelles, Boulevard du Triomphe accès 2, B-1050 Bruxelles, Belgium.
authors.forename: Bieke
authors.initials: B
authors.lastname: Dejaegher
authors.affiliation: Laboratory of Micro- and Photoelectronics, LAMI-ETRO, Vrije Universiteit Brussel, Pleinlaan 2, B-1050 Brussels, Belgium.
authors.forename: Johan
authors.initials: J
authors.lastname: Stiens
authors.affiliation: Department of Analytical Chemistry and Pharmaceutical Technology, Center for Pharmaceutical Research, Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090 Brussels, Belgium.
authors.forename: Debby
authors.initials: D
authors.lastname: Mangelings
authors.affiliation: Department of Analytical Chemistry and Pharmaceutical Technology, Center for Pharmaceutical Research, Vrije Universiteit Brussel, Laarbeeklaan 103, B-1090 Brussels, Belgium. Electronic address: yvanvdh@vub.ac.be.
authors.forename: Yvan
authors.initials: Y
authors.lastname: Vander Heyden
mesh_terms: D019075:Electrophoresis, Capillary / Q000295:instrumentation / Q000379:methods*; D015203:Reproducibility of Results; D013237:Stereoisomerism; D013997:Time Factors
keywords: Analytical method transfer; Capillary electrophoresis; Chiral separation; Constant current; Joule heating; Precision