title: A simple and efficient approach to reversed-phase HPLC method screening.
abstract: The development and utility of an efficient HPLC method screening strategy using only four columns for the separation of pharmaceutical compounds and related impurities is presented. The strategy established a two-column approach to enable rapid early method development, along with a four-column approach for commercial method development of the analytical methods utilized to verify the quality of drug substance or drug product. Mobile phases consisted of acetonitrile or methanol with aqueous trifluoroacetic acid for low pH screening, and ammonium hydroxide for high pH screening. Examples are provided to demonstrate the practicality and orthogonality of the method screening process. A unique system suitability check, using commercially available compounds, was incorporated as a tool for troubleshooting and for ensuring adequate system performance prior to screening. Initial testing of the strategy revealed that the columns chosen were successful in leading to assay and impurity methods for 40 pharmaceutical compounds.
authors.affiliation: Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA.
authors.forename: Kallol M
authors.initials: KM
authors.lastname: Biswas
authors.forename: Bryan C
authors.initials: BC
authors.lastname: Castle
authors.forename: Bernard A
authors.initials: BA
authors.lastname: Olsen
authors.forename: Donald S
authors.initials: DS
authors.lastname: Risley
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Skibic
authors.forename: Paul B
authors.initials: PB
authors.lastname: Wright
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006863:Hydrogen-Ion Concentration; D007202:Indicators and Reagents; D013058:Mass Spectrometry; D015233:Models, Statistical; D004364:Pharmaceutical Preparations / Q000032:analysis*; D015203:Reproducibility of Results; D054852:Small Molecule Libraries; D012984:Software; D013056:Spectrophotometry, Ultraviolet; D013696:Temperature
chemical_list: D007202:Indicators and Reagents; D004364:Pharmaceutical Preparations; D054852:Small Molecule Libraries