Reduction of Ion Suppression and Interference using Turbulent Flow Chromatography and FAIMS for Drug Discovery Bioanalysis

摘要

Liquid chromatography/tandem mass spectrometry has been the standard experimental approach for the quantitation of drugs and their metabolites in support of in-vivo pharmacokinetic studies for the past twenty years. However, since the first report of ion suppression and its effect on drug quantitation (1) scientists have been devising ways to measure, eliminate, or at least mitigate its adverse effects. This problem is exacerbated by compounds such as PEG 400 used for the formulation of drug molecules: They can create severe ion suppression in samples taken from dosed animals and are not necessarily contained in the blank plasma used to prepare standard curves and QC samples. In this presentation the use of parallel on-line extraction of PEG 400 from in-vivo PK studies is described. The method employs turbulent flow chromatography for on-line extraction with a run-time of less than 5 minutes. In addition, a field asymmetric ion mobility (FAIMS) ion source is used to eliminate remaining isobaric interferences.