Extra-column band broadening effects in contemporary liquid chromatography: Causes and solutions

Columns for liquid chromatography produce ever narrower peaks and analysts continue to push to smaller column diameters to save solvents and have better MS responses. The combined effect of both trends is that the instrument volumes outside the separation column (=extra-column volumes of the instrument) become a significant contributor to the overall dispersion. This currently occurs to such an extent that the current state-of-the-art chromatographic columns have become too good compared to the quality of most instruments. Extra-column dispersion also becomes very critical in the now rapidly emerging multi-dimensional LC application area. The present contribution reviews past and recent studies of the experimental and theoretical work conducted thus far to measure, predict and optimize extra-column dispersion. Emphasis is put on providing some general rules that can be followed to minimize extra-column dispersion in the most efficient way (i.e., without sacrificing too much of the available pressure or detection sensitivity). (C) 2019 Elsevier B.V. All rights reserved.