Analytical bias between species caused by matrix effects in quantitative analysis of a small-molecule pharmaceutical candidate in plasma

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. Conclusion: A simple strategy to assess the potential of any unmitigated matrix effect to bias quantitative analysis by nonequivalent ionization induction or suppression is evaluated.