Comprehensive liquid chromatography: fundamental aspects and practical considerations--a review.

In the quest for separation techniques capable of generating high peak capacities, comprehensive two-dimensional (2D) liquid chromatography (LC x LC) is a performant analytical tool for the analyses of complex mixtures. Interest in LC x LC has increased substantially over the past few years. The most significant and profitable difference between LC x LC and other multidimensional (MD) LC approaches is the subjection of every part of the sample to two individual separation dimensions. This results in a tremendous increase in resolving power, since the peak capacity of the comprehensive system approaches the product of the peak capacities of the first and second dimension separations when highly orthogonal separation mechanisms are combined. The present review discusses the theoretical aspects of LC x LC together with practical considerations for LC x LC method development. An extensive overview of different interface designs discussing their pros and cons is presented.