title: High performance liquid chromatographic enantioseparation development and analytical method characterization of the carboxylate ester of evacetrapib using an immobilized chiral stationary phase with a non-conventional eluent system.
abstract: Using multiple HPLC chromatographic modes and various chiral columns in the context of an automated screening system, a potential separation was initially identified for the methyl ester of evacetrapib and its stereoisomers using an immobilized polysaccharide-based HPLC column. The bonded nature of this column, the Chiralpak(®) IC, allows for enhanced separation development with a diverse solvent range not amenable to standard coated chiral stationary phases. The ternary eluent system ultimately identified provided isomer resolutions not obtainable via the more established hexane/alcohol or polar organic chromatographic modes. A systematic separation development process is described, first for the resolution of the isomers, and later incorporating five potential impurities. A robust separation system was eventually developed that effectively resolves all compounds within a reasonable analysis time.
authors.affiliation: Process Design and Development, Small Molecule Design and Development, Eli Lilly and Company, Lilly Technology Center South, Indianapolis, IN 46221, USA. Electronic address: vss@lilly.com.
authors.forename: V Scott
authors.initials: VS
authors.lastname: Sharp
authors.affiliation: Product Design and Developability, Small Molecule Design and Development, Eli Lilly and Company, Lilly Technology Center North, Indianapolis, IN 46221, USA.
authors.forename: Megan A
authors.initials: MA
authors.lastname: Gokey
authors.affiliation: Statistics - Discovery & Development, Eli Lilly and Company, Lilly Technology Center South, Indianapolis, IN 46221, USA.
authors.forename: Chad N
authors.initials: CN
authors.lastname: Wolfe
authors.affiliation: Process Design and Development, Small Molecule Design and Development, Eli Lilly and Company, Lilly Technology Center South, Indianapolis, IN 46221, USA.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Rener
authors.affiliation: Product Design and Developability, Small Molecule Design and Development, Eli Lilly and Company, Lilly Technology Center North, Indianapolis, IN 46221, USA.
authors.forename: Mary R
authors.initials: MR
authors.lastname: Cooper
mesh_terms: D000924:Anticholesteremic Agents / Q000032:analysis / Q000737:chemistry / Q000302:isolation & purification; D001569:Benzodiazepines / Q000032:analysis / Q000737:chemistry* / Q000302:isolation & purification*; D002264:Carboxylic Acids / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004952:Esters / Q000737:chemistry*; D000431:Ethanol / Q000737:chemistry; D011134:Polysaccharides / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D000924:Anticholesteremic Agents; D002264:Carboxylic Acids; D004952:Esters; D011134:Polysaccharides; D012997:Solvents; D001569:Benzodiazepines; D000431:Ethanol; C568301:evacetrapib
keywords: Chiral separation; Enantiomer; Immobilized stationary phase; Isomer; Mid-polarity solvents