Generic capillary electrophoresis conditions for chiral assay in early pharmaceutical development

Abstract

Generic capillary electrophoresis (CE) conditions have been implemented for chiral separations in early pharmaceutical development. The chiral CE separations of several pharmaceutical samples at different stages of development, i.e., discovery, process chemistry, and investigative new drug application, have been obtained using sulfated beta-cyclodextrin (CD). Several sulfated beta-CDs have been screened to select an appropriate enantioselective agent. The use of a generic CE method allows for a convenient and rapid chiral recognition of different weak bases, with minimal or no method development. CE using sulfated beta-CD for the chiral separation of N-benzoyl methyl piperazine has been validated for linearity, precision, accuracy, limits of detection and quantitation (LOD, LOQ). Although less sensitive than a specific liquid chromatography method using a Chiralpak AD column, the overall performance of the chiral CE method was found comparable. Validation data demonstrate that a LOD of 0.1%, sufficient to fulfill regulatory requirements, is achievable by chiral CE.

Review of aqueous chiral electrokinetic chromatography (EKC) with an emphasis on chiral microemulsion EKC

“…Rocheleau [90] compared S-b-CDs with different degrees of substitution for five pharmaceutical compounds. Enantioseparations were better when the selectand was more substituted.…”

Method for enantiomeric purity of a quinuclidine candidate drug by capillary electrophoresis

“…CDs are by far the principal chiral selectors in use [25], formerly dominated by derivatized, neutral CDs [13,26] and more recently charged by principally sulfated CDs [18, 27 -29]. A number of authors have proposed generic approaches to the use of CDs for rapid testing of pharmaceutical compounds [24,25,30,31].…”

Capillary electrophoresis for the analysis of small‐molecule pharmaceuticals

“…Rocheleau [53] (Bristol-Myers Squibb) used only sulphated b-CDs in her screen, and additionally evaluated the different suppliers and batches of CD. The approach has been successfully applied to more than a dozen of the company's compounds in different phases of development.…”