Minimizing matrix effects while preserving throughput in LC-MS/MS bioanalysis
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Updated: May 31, 2026
Large Scale Non-targeted Metabolomic Profiling of Serum by Ultra Performance Liquid Chromatography-Mass Spectrometry (UPLC-MS)
Published on: March 14, 2013
Zhengqi Ye1, Hong Tsao, Hong Gao
1Drug Innovation Pharmacokinetics, Vertex Pharmaceuticals Inc., Cambridge, MA 02139, USA.
Background:
Phospholipids are known to cause matrix effects in LC-MS analysis and are not effectively removed by one of the most common method of sample preparation: organic solvent protein precipitation. The objective of this research is to minimize phospholipid interferences chromatographically.
Results:
In this article we examine several chromatographic approaches and highlight the method we developed that allows for the rapid gradient separation of model drug molecules from phospholipids.
Conclusion:
The new approach (which utilizes a mixture of methanol and acetonitrile as the organic mobile phase on a 2.1 × 20 mm C18 column) minimized phospholipids-related matrix effects in the analysis of plasma samples prepared by protein precipitation and is suitable for high-throughput bioanalysis in drug discovery.
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