Journal
TALANTA
Volume 80, Issue 3, Pages 1406-1412Publisher
ELSEVIER
DOI: 10.1016/j.talanta.2009.09.043
Keywords
Matrix effects; Bio-matrices; Pulse gradient with ammonium formate effects; Pharmacokinetic study; LC-ESI-MS/MS; Protein precipitation
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Funding
- Chinese Ministry of Science and Technology [2004CB518902, 2005CB523403]
- Science & Technology Commission of Shanghai Municipality [04DZ19215]
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This study compares and evaluates the effect of various matrices on liquid chromatography (LC) coupled with tandem mass spectrometry (MS/MS) analysis. Permanent post-column infusion (PCI) was used to quantify matrix effects. In this way, the suppressed or enhanced signal of the target material resulting from different co-eluting matrix components could be assessed. Twenty-four biological samples from in vivo and in vitro experiments were selected for this study. In addition, 7 sample components were further analyzed after sample preparation by protein precipitation. Multiple regression analysis was used to investigate the collinear relationship between matrix effects and co-eluted components at different time intervals. We found that salt was the dominant factor which impacted changes in signal detection. In order to eliminate it, we used ammonium formate as a modifier of the mobile phase which resulted in charge-state redistribution profiles so that a homogeneous matrix formed. By employing pulse gradient chromatography in the presence of 5 mM ammonium formate, favorable improvements of enhanced signal intensity and reduced matrix effects were obtained. These experiments also indicated the feasibility of using analogue IS during bio-analysis which contributed to an overall faster assay that would be suitable for drug discovery and development purposes. (C) 2009 Elsevier B.V. All rights reserved
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