Matrix Effects on Quantitation in Liquid Chromatography: Sources and Solutions

The “matrix effect” is one of the sticky details that can make the use of liquid chromatography (LC) for quantitative purposes challenging, even though it is conceptually quite straightforward. In this installment, I review what we are referring to when we talk about “matrix effects,” and discuss some of the potential origins of the phenomenon in practice. I then go on to describe some of the commonly-used approaches to mitigate these effects, providing a path to accurate and precise results, even when working with highly complex sample matrices. As with many troubleshooting topics, developing a solid understanding of matrix effects on quantitation and potential strategies for mitigation can be helpful, both during the development of new methods to prevent future problems, and troubleshooting problems with quantitation observed with existing methods.