title: Utilizing a -100 degrees C microplate CCD Imager, yttrium silicate coated 384-microplates and ultra-performance liquid chromatography for improved profiling of radiolabeled drug metabolites in complex biological samples.
abstract: The recent commercial availability of small particle packed columns (<2 microm) and associated instrumentation capable of withstanding the high pressures of such columns, has lead to an increase in the application of so called ultra-performance liquid chromatography. The improved efficiency, resolution and peak capacity of these columns, when coupled to mass spectrometry, provides particular benefit for the identification of drug metabolites in complex biological samples. In this work, the ability of ViewLux, a microplate imager, to act as a suitable radiodetection system for ultra-performance liquid chromatography methods is assessed. The system demonstrates robustness and sensitivity comparable to a microplate scintillation counter (TopCount) more typically used for off-line metabolite radiodetection. The ViewLux is also used here to undertake successful metabolite profiling of actual samples, for two investigational drug candidates, using both 96- and 384-well yttrium silicate microplates.
authors.affiliation: DMPK, GlaxoSmithKline R&D, Ware, Hertfordshire, UK. gordon.j.dear@gsk.com
authors.forename: G J
authors.initials: GJ
authors.lastname: Dear
authors.forename: N
authors.initials: N
authors.lastname: Patel
authors.forename: Alan
authors.initials: A
authors.lastname: Weightman
authors.forename: Hans
authors.initials: H
authors.lastname: Pirard
authors.forename: Miika
authors.initials: M
authors.lastname: Talvitie
mesh_terms: D000818:Animals; D001646:Bile / Q000737:chemistry; D002853:Chromatography, Liquid / Q000379:methods*; D003080:Cold Temperature; D066298:In Vitro Techniques; D008099:Liver / Q000737:chemistry; D013058:Mass Spectrometry / Q000379:methods; D004364:Pharmaceutical Preparations / Q000032:analysis*; D011868:Radioisotopes; D051381:Rats; D012015:Reference Standards
chemical_list: D004364:Pharmaceutical Preparations; D011868:Radioisotopes