title: Cytostar-T plates--a valid alternative for microplate scintillation counting of low radioactivity in combination with high-performance liquid chromatography in drug metabolism studies?
abstract: The determination of radioactivity from metabolite patterns in ADME studies in a low radioactivity/residue situation is a very challenging process requiring special technologies. The recently introduced TopCount technology uses LumaPlates for the collection of the column effluent after HPLC separation to subsequently determine radioactivity for the generation of the metabolite profile. Samples from drug metabolism studies were used to compare the performance of the widely used LumaPlates with Cytostar-T plates regarding sensitivity and recovery of metabolites for structure elucidation by MS. Optimized counting parameters were investigated for the Cytostar-T plates. This had led to higher sensitivity and therefore to a preferential signal to noise ratio. Metabolites which were collected into Cytostar-T instead of LumaPlates could be easily recovered and directly used for structure elucidation by MS. The full scan mass spectra of recovered metabolites showed higher quality allowing the characterization of metabolites without any further sample pre-treatment. This is a major advantage which could further speed-up the structure elucidation process of metabolites in complex biological matrices.
authors.affiliation: Novartis Pharma AG, Metabolism and pharmacokinetics (MAP), WSJ-360.2.02, CH-4002 Basel, Switzerland. michael.kiffe@novartis.com
authors.forename: Michael
authors.initials: M
authors.lastname: Kiffe
authors.forename: Robert
authors.initials: R
authors.lastname: Nufer
authors.forename: Markus
authors.initials: M
authors.lastname: Trunzer
authors.forename: Daniel
authors.initials: D
authors.lastname: Graf
mesh_terms: D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D013058:Mass Spectrometry; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism*; D012588:Scintillation Counting; D012680:Sensitivity and Specificity
chemical_list: D004364:Pharmaceutical Preparations