Opportunities and challenges of liquid chromatography coupled to supercritical fluid chromatography

The analysis of complex samples is facilitated by the emergence of two-dimensional liquid chromatography.Despite optimization efforts to reach tremendous peak capacities, the separation of neutral compounds remains limited.Indeed, most combinations of chromatographic modes suffer either from a lack of orthogonality or from serious solvent incompatibilities.The two-dimensional separation involving a combination of liquid chromatography and supercritical fluid chromatography seems to offer new opportunities for the separation of ionizable and neutral solutes.This review highlights the orthogonality the combination can offer thanks to a wide range of stationary phases.Injection effects occurring in SFC, that may drastically reduce the performances of online LC x SFC are also discussed in details.Finally, despite net improvement in SFC instrumentation in the recent years, instrumental limitations still have to be overcome.While this review highlights the potential of LC and SFC combination and its complementarity with 2D-LC, it also demonstrates that its development requires the joint efforts of researchers and instrumental suppliers before comprehensive LC x SFC gets adopted by the scientific community.