title: Universal LC-MS method for minimized carryover in a discovery bioanalytical setting.
abstract: BACKGROUND
  A frequent impediment to accurate quantitation in bioanalytical LC-MS arises from carryover. For many new chemical entities in drug discovery carryover is not limited to the autosampler, but instead arises from several different sources.
  
  
  METHODS
  We tested several different columns, injector wash sequences and gradient compositions to understand and eliminate these sources. In many instances carryover was dictated by the elution gradient and column as much as the autosampler hardware and wash protocol.
  
  
  CONCLUSIONS
  Several trends were observed. First, different columns resulted in significantly different amounts of carryover (even for nominally the same column chemistry). Second, a continuous high organic wash of the column was not as effective at removing carryover as cycling between high and low organic mobile phases during the column wash. Combining our observations (column, gradient and autosampler configuration) we devised a short 3-min method that is appropriate for a diverse set of new chemical entities and minimizes carryover while still being sufficiently robust to use in a drug-discovery setting.
authors.affiliation: Vertex Pharmaceuticals, Inc., 130 Waverley St, Cambridge, MA 02139, USA.
authors.forename: John S
authors.initials: JS
authors.lastname: Williams
authors.forename: Stephanie H
authors.initials: SH
authors.lastname: Donahue
authors.forename: Hong
authors.initials: H
authors.lastname: Gao
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Brummel
mesh_terms: D000818:Animals; D001331:Automation; D002626:Chemistry, Pharmaceutical / Q000379:methods / Q000592:standards; D002851:Chromatography, High Pressure Liquid / Q000379:methods* / Q000592:standards; D013058:Mass Spectrometry / Q000379:methods* / Q000592:standards; D004364:Pharmaceutical Preparations / Q000032:analysis*; D010949:Plasma / Q000737:chemistry; D011786:Quality Control; D051381:Rats
chemical_list: D004364:Pharmaceutical Preparations