Advances in Online Comprehensive Two-Dimensional Liquid Chromatography Method Development

Comprehensive two-dimensional liquid chromatography (LC×LC) is increasingly being used to provide new information on the composition of complex samples. More widespread use of the technique is, however, hampered by the complexity of method development, which involves the selection and optimization of a very large number of experimental variables while considering their interdependence and relationship with conflicting analysis goals. This contribution summarizes the progress made in online LC×LC method development to date. Recent trends in advanced method optimization are highlighted to demonstrate how progress in the field enables the development of highly efficient LC×LC methods.