Overcoming ionization effects through chromatography: A case study for the ESI-LC–MS/MS quantitation of a hydrophobic therapeutic agent in human serum using a stable-label internal standard

Significant electrospray ionization effects were observed for a hydrophobic analyte and its stable isotopically labeled internal standard (SIL IS) in human plasma extracts. Analyte and SIL IS were slightly offset in retention within the suppression region resulting in a differential suppression that...

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Bibliographic Details
Published in:Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Analytical technologies in the biomedical and life sciences, 2009-07, Vol.877 (22), p.2003-2010
Main Authors: Zhang, Guodong, Wujcik, Chad E.
Format: Article
Language:English
Subjects:
Analysis
Analytical, structural and metabolic biochemistry
Anti-Obesity Agents - blood
Biological and medical sciences
Chromatography, High Pressure Liquid - methods
Fundamental and applied biological sciences. Psychology
General pharmacology
Humans
LC–MS/MS
log D
Matrix effects
Medical sciences
Obesity - drug therapy
Pharmacology. Drug treatments
Phospholipids
Phospholipids - blood
Reference Standards
Serum
Spectrometry, Mass, Electrospray Ionization - methods
Stable isotopically labeled (SIL) internal standard
Tandem Mass Spectrometry - methods
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Summary:Significant electrospray ionization effects were observed for a hydrophobic analyte and its stable isotopically labeled internal standard (SIL IS) in human plasma extracts. Analyte and SIL IS were slightly offset in retention within the suppression region resulting in a differential suppression that biased calculated concentrations. Six abundant endogenous phospholipids were identified as potential contributors to ionization suppression. Chromatographic conditions were optimized using pH (relative to the logD of the analytes), to better resolve nearby phospholipids from the analyte and SIL IS and minimize ionization suppression. The successful validation of this method demonstrates the value of investigating minor chromatographic changes to remediate detrimental ionization effects without further altering extraction procedures.
ISSN:1570-0232
1873-376X
DOI:10.1016/j.jchromb.2009.05.031