Elimination of LC-MS/MS matrix effect due to phospholipids using specific solid-phase extraction elution conditions
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Updated: Jun 6, 2026

Cellular Lipid Extraction for Targeted Stable Isotope Dilution Liquid Chromatography-Mass Spectrometry Analysis
Published on: November 17, 2011
Mathieu Lahaie1, Jean-Nicholas Mess, Milton Furtado
1Algorithme Pharma Inc., Laval (Montreal), Quebec, Canada.
Background:
The objective is to find elution conditions using different solid-phase extraction chemistries to reduce the amount of phospholipids in plasma extract, which is associated with matrix effect in LC-MS.
Results:
Phospholipids' recovery was reduced by decreasing the eluents' methanol content applied to silica-based and polymer-based reversed-phase solid-phase extraction cartridges while 100% acetonitrile applied to the silica-based cartridges drastically minimized the phospholipids' elution. Silanol interactions are involved in the increased retention of phospholipids with silica-based reversed-phase cartridges when using high percentages of ACN in eluents. The bioanalytical usefulness of these findings was confirmed by successful extraction recovery of pharmaceutical compounds.
Conclusion:
Combinations of specific eluents and reversed-phase solid-phase extraction cartridges were found to prevent matrix effect due to phospholipids.
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