Perspectives on addressing ionization matrix effects in LC-MS bioanalysis

Ionization matrix effects are one of the most difficult issues in LC-MS bioanalysis that are without a good and universal solution. Most people in the field are aware of it, but some are not sure how to deal with it. Many laboratories do not routinely assess matrix effects in method validation or substitute it with a different experiment that only indirectly and partially test matrix effects. Others, when matrix effects are mentioned, immediately link them with phospholipids and try to use means to remove them from the samples (e.g., SPE), without understanding if the phospholipids can really impact the analytes. In this article, key issues related to matrix effects will be examined, and methods to address matrix effect problems will be evaluated for effectiveness and practicality.