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Comprehensive two-dimensional liquid chromatography(LC × LC) is a powerful tool for the separation of complex samples.In LC × LC system, the second dimensional column should ideally be eluted at very high speed to meet the rate of fractionation at the first dimensional separation, as practiced in comprehensive two-dimensional gas chromatography.High pressure capability of rapid resolution liquid chromatography can generate very fast run in short column.With small particles used in analytical column, separation can be run with high speed and high efficiency.Therefore, rapid resolution liquid chromatography is well suited to use as the second dimensional column of an LC × LC system.