A separation that occurs in a single column caused by the retention and selectivity provided by a dual-retention mechanism. For example, a reversed-phase column with residual silanols at intermediate-to-high pH values can separate by hydrophobic interaction and ionic interaction by the ionized silanols. Sometimes mixed-mode separations can be quite beneficial to the selectivity (band spacing), but they can cause peak asymmetry, and the precise balance of interactions may be difficult to reproduce with subsequent packing batches.