title: Stereoselective high-performance liquid chromatography and analytical method characterization of evacetrapib using a brush-type chiral stationary phase: a challenging isomeric separation requiring a unique eluent system.
abstract: Using HPLC chiral separation screening, various columns representing the polysaccharide, macrocyclic antibiotic and brush classes were assessed in multiple chromatographic modes for the separation of evacetrapib, a potential cardiovascular drug, from its enantiomer, two diastereomers and several impurities. Screening data consistently pointed to the brush-type Whelk-O 1 chiral column as most promising for this task. A systematic separation optimization process is outlined using the (S,S) Whelk-O 1 chiral column, first for the resolution of the isomers, and later including six potential impurities. A relatively complex yet rugged separation system was eventually identified that effectively resolves all compounds within a reasonable analysis time, and should serve as an adequate tool for evacetrapib bulk drug enantiopurity measurement.
authors.affiliation: Product Design and Developability, Small Molecule Design and Development, Eli Lilly and Company, Lilly Technology Center North, Indianapolis, IN 46221, USA. Electronic address: vss@lilly.com.
authors.forename: V Scott
authors.initials: VS
authors.lastname: Sharp
authors.affiliation: Product and Process Performance, Small Molecule Design and Development, Eli Lilly and Company, Lilly Technology Center South, Indianapolis, IN 46221, USA.
authors.forename: John D
authors.initials: JD
authors.lastname: Stafford
authors.affiliation: Product and Process Performance, Small Molecule Design and Development, Eli Lilly and Company, Lilly Technology Center South, Indianapolis, IN 46221, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Forbes
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: 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: D001569:Benzodiazepines / Q000032:analysis*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D007202:Indicators and Reagents; D013237:Stereoisomerism
chemical_list: D007202:Indicators and Reagents; D001569:Benzodiazepines; C568301:evacetrapib
keywords: Brush; Chiral; Enantiomer; Evacetrapib; Pirkle; Whelk O-1