title: Automated solvent system screening for the preparative countercurrent chromatography of pharmaceutical discovery compounds.
abstract: A fully automated countercurrent chromatography system has been constructed to rapidly screen the commonly used heptane/ethyl acetate/methanol/water solvent system series and translate the results to preparative scale separations. The system utilizes "on-demand" preparation of the heptane/ethyl acetate/methanol/water solvent system upper and lower phases. Elution-extrusion countercurrent chromatography was combined with non-dynamic equilibrium injection reducing the screening time for each heptane/ethyl acetate/methanol/water system to 17 min. The result enabled solvent system development to be reduced to under 2 h. The countercurrent chromatography system was interfaced with a mass spectrometer to allow selective detection of target components in crude medicinal chemistry reaction mixtures. Mass-directed preparative countercurrent chromatography purification was demonstrated for the first time using a synthetic tetrazole epoxide derived from a routine medicinal chemistry support workflow.
authors.affiliation: Pfizer Research & Development, Groton, CT, USA.
authors.forename: James
authors.initials: J
authors.lastname: Bradow
authors.affiliation: Pfizer Research & Development, Groton, CT, USA.
authors.forename: Frank
authors.initials: F
authors.lastname: Riley
authors.affiliation: Pfizer Research & Development, Groton, CT, USA.
authors.forename: Laurence
authors.initials: L
authors.lastname: Philippe
authors.affiliation: Pfizer Research & Development, Groton, CT, USA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Yan
authors.affiliation: Pfizer Research & Development, Groton, CT, USA.
authors.forename: Brandon
authors.initials: B
authors.lastname: Schuff
authors.affiliation: Dynamic Extractions, Inc., Monmouth Junction, NJ, USA.
authors.forename: Guy H
authors.initials: GH
authors.lastname: Harris
mesh_terms: D001331:Automation; D002851:Chromatography, High Pressure Liquid; D003377:Countercurrent Distribution; D055808:Drug Discovery / Q000379:methods*; D057230:Limit of Detection; D013058:Mass Spectrometry; D015394:Molecular Structure; D012997:Solvents / Q000737:chemistry
chemical_list: D012997:Solvents
keywords: Automation; Countercurrent chromatography; Elution-extrusion; Mass-directed separation; Preparative chromatography