Minimizing matrix effects while preserving throughput in LC-MS/MS bioanalysis

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 x 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.