title: Analytical bias between species caused by matrix effects in quantitative analysis of a small-molecule pharmaceutical candidate in plasma.
abstract: BACKGROUND
  Suppression or enhancement of MS ionization, particularly evident when electrospray is used as the source of ions, has been widely discussed.
  
  
  METHODS
  An assay for a small-molecule pharmaceutical in dog plasma between 1-300 ng/ml was validated with a mean bias across the calibration range of 5.0%. When the calibration sample matrix was substituted for human plasma, the mean bias across the range increased to 29.1%. A study of bias originating as a result of matrix effects, arising from endogenous glycerophosphocholine species, in plasma sources is discussed.
  
  
  CONCLUSIONS
  A simple strategy to assess the potential of any unmitigated matrix effect to bias quantitative analysis by nonequivalent ionization induction or suppression is evaluated.
authors.affiliation: Covance, Alnwick, Northumberland, UK.
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: Gray
authors.forename: Stuart A
authors.initials: SA
authors.lastname: McDougall
authors.forename: John R
authors.initials: JR
authors.lastname: Dean
mesh_terms: D000818:Animals; D001549:Benzamides / Q000097:blood; D002853:Chromatography, Liquid; D003903:Deuterium / Q000737:chemistry; D004285:Dogs; D005997:Glycerylphosphorylcholine / Q000032:analysis; D006801:Humans; D007211:Indoles / Q000097:blood; D016018:Least-Squares Analysis; D051379:Mice; D004364:Pharmaceutical Preparations / Q000097:blood*; D011817:Rabbits; D051381:Rats; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: C484315:(4-chloro-3-((3R)-(+)-5-chloro-1-(2,4-dimethoxybenzyl)-3-methyl-2-oxo-2,3-dihydro-1H-indol-3-yl))-N-ethyl-N-(3-pyridylmethyl)-benzamide, hydrochloride; D001549:Benzamides; D007211:Indoles; D004364:Pharmaceutical Preparations; D005997:Glycerylphosphorylcholine; D003903:Deuterium