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 × 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 × SFC gets adopted by the scientific community.

二维液相色谱的出现促进了复杂样品的分析。尽管进行了优化以达到巨大的峰容量，但中性化合物的分离仍然有限。事实上，大多数色谱模式组合要么缺乏正交性，要么存在严重的溶剂不相容性。结合液相色谱和超临界流体色谱的二维分离似乎为分离可电离溶质和中性溶质提供了新的机会。这篇综述强调了该组合可以提供的正交性，这要归功于广泛的固定相。还详细讨论了 SFC 中发生的注入效应，这可能会大大降低在线 LC × SFC 的性能。最后，尽管近年来 SFC 仪器取得了净改进，但仍需克服仪器限制。虽然这篇综述强调了 LC 和 SFC 组合的潜力及其与二维 LC 的互补性，但它也表明，在综合 LC × SFC 被科学界采用之前，它的发展需要研究人员和仪器供应商的共同努力。