Perspectives on the Use of Retention Modeling to Streamline 2D-LC Method Development: Current State and Future Prospects

Abstract

The history of multidimensional liquid chromatography (MDLC) has been dominated by methods that have been developed using highly empirical, experience-driven, trial-and-error approaches. These approaches have been sufficient in progressing the field forward scientifically, primarily in academic research laboratories. However, more widespread usage of multidimensional separations will require more systematic approaches to method development that rely less on user experience and lower the barriers to development and use of methods by a wider community of users. In this mini-review, we discuss recent research aimed at developing such systematic, model-driven approaches to streamline method development and speculate about likely advances in the same direction in the near future. It seems likely that such model-driven approaches would be particularly helpful for methods developed for analyzing biopharmaceutical molecules, which tend to be very sensitive to slight changes in method conditions (for example, mobile phase composition).