title: A screening strategy for the development of enantiomeric separation methods in capillary electrophoresis.
abstract: Method development of enantiomeric separations in capillary electrophoresis (CE) is a time-consuming task, since finding the appropriate chiral selector is usually a "trial and error" process. It is impossible to predict the selectivity of a selector towards a certain enantiomer. Therefore, the affinity of all selectors has to be examined one at a time. In order to speed up this process, a strategy is proposed based on simple experimental design methodology. The approach includes first a screening in function of the pH to determine the optimal migration conditions followed by a selection of the right chiral selector by means of Taguchi designs. In the approach several variables, such as the type and concentration of cyclodextrin, the concentration of buffer electrolyte, and the percentage of organic modifier, are varied simultaneously to find initial separation conditions rapidly. The resulting initial separation conditions can be optimized in further steps to be more reproducible. We discuss the results of the approach when applied on a number of selected compounds that are recently in development at Johnson & Johnson--Pharmaceutical Research and Development. Parameters, such as quality of the separation and analysis time, are evaluated to determine initial separation conditions for each compound.
authors.affiliation: Johnson & Johnson Pharmaceutical Research & Development (J&J-PRD), A division of Janssen Pharmaceutica n.v., Global Analytical Development, Beerse, Belgium. ijimidar@prdbe.jnj.com
authors.forename: M Ilias
authors.initials: MI
authors.lastname: Jimidar
authors.forename: Willy
authors.initials: W
authors.lastname: Van Ael
authors.forename: Patrick
authors.initials: P
authors.lastname: Van Nyen
authors.forename: Margot
authors.initials: M
authors.lastname: Peeters
authors.forename: Dirk
authors.initials: D
authors.lastname: Redlich
authors.forename: Maurits
authors.initials: M
authors.lastname: De Smet
mesh_terms: D003505:Cyclodextrins; D019075:Electrophoresis, Capillary / Q000295:instrumentation / Q000379:methods* / Q000706:statistics & numerical data; D006863:Hydrogen-Ion Concentration; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000302:isolation & purification; D012996:Solutions; D013237:Stereoisomerism
chemical_list: D003505:Cyclodextrins; D004364:Pharmaceutical Preparations; D012996:Solutions