title: Fast method development and rapid analysis using a screening approach for enantiomeric separations in capillary electrophoresis.
abstract: In order to speed up the trial-and-error process during enantioselective capillary electrophoresis methods development, a systemized approach is proposed to develop methods by applying several screening methods in the search for an initial separation. Screening methods combine high selectivity with broad applicability and are applied to find an initial enantiomeric separation during early pharmaceutical development (pre-Phase 1 to Phase 1). The goal is to achieve enantiomeric separation rapidly in order to characterize the chiral purity of pharmaceutical products. Dedicated, highly efficient screening methods are suggested for basic, neutral, and acidic compounds. In these screening methods, multiple chiral selectors are applied in mixtures at different buffer pH values. For the compounds studied, the technique allows fast method development. Furthermore, it is potentially applicable to a wide range of low-molecular-weight compounds and permits rapid analysis at low cost, since runs are performed in inexpensive, bare silica capillaries using ordinary buffer systems with only typical cyclodextrins as the selector. Along with simplicity and robustness, the approach results in sufficient efficacy (i.e., it is easy, straightforward, and reproducible, with a high success rate). Typical pharmaceutical applications are described. The major advantage of the screening approach to methods development is the decrease in development cycle time. The total screening time for one compound was about 5.3 hr on one CE instrument.
authors.affiliation: Global Analytical Development, Johnson & Johnson Pharmaceutical Research & Development, A Div. of Janssen Pharmaceutica N.V., 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: Rekha
authors.initials: R
authors.lastname: Shah
authors.forename: Dirk
authors.initials: D
authors.lastname: Redlich
authors.forename: Maurits
authors.initials: M
authors.lastname: De Smet
mesh_terms: D045424:Complex Mixtures / Q000032:analysis* / Q000737:chemistry; D003505:Cyclodextrins / Q000032:analysis* / Q000737:chemistry* / Q000145:classification; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D019075:Electrophoresis, Capillary / Q000379:methods*; D004364:Pharmaceutical Preparations / Q000032:analysis* / Q000737:chemistry*; D011785:Quality Assurance, Health Care / Q000379:methods; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013237:Stereoisomerism
chemical_list: D045424:Complex Mixtures; D003505:Cyclodextrins; D004364:Pharmaceutical Preparations