Method of separating a mixture in a system comprising a plurality of chromatography columns, the method successively comprising, in a cyclic manner, in a given part of the system: - a step of collecting a raffinate, a step of injecting the mixture to be separated, a step of collecting an extract, and a step of injecting a mobile phase; the system comprising areas 1, 2, 3 and 4, area 1 being located between a mobile phase injection line and a line for collecting the extract, area 2 being located between said line for collecting the extract and a line for injecting the mixture to be separated, area 3 being located between said line for injecting the mixture to be separated and a line for collecting the raffinate, and area 4 being located between said line for collecting the raffinate and said mobile phase injection line; wherein the method further comprises: - the determination, in a node of the system, of the history of a variable that is representative of the concentration of one or more species contained in the mixture to be separated; - the detection on said history of a single characteristic point in the portion of the history corresponding to area 1, area 4 and the interface between these two areas; - the comparison of the position of the characteristic point against a target position; - the adjustment of the carrying volume of area 1 and/or the carrying volume of area 4, modifying the position of the characteristic point to bring the position of the characteristic point closer to the target position; - the volume of the mobile phase injected per cycle being maintained greater than, or equal to, a minimum limit and/or less than, or equal to, a maximum limit. - a step of collecting a raffinate, a step of injecting the mixture to be separated, a step of collecting an extract, and a step of injecting a mobile phase; the system comprising areas 1, 2, 3 and 4, area 1 being located between a mobile phase injection line and a line for collecting the extract, area 2 being located between said line for collecting the extract and a line for injecting the mixture to be separated, area 3 being located between said line for injecting the mixture to be separated and a line for collecting the raffinate, and area 4 being located between said line for collecting the raffinate and said mobile phase injection line; wherein the method further comprises: - the determination, in a node of the system, of the history of a variable that is representative of the concentration of one or more species contained in the mixture to be separated; - the detection on said history of a single characteristic point in the portion of the history corresponding to area 1, area 4 and the interface between these two areas; - the comparison of the position of the characteristic point against a target position; - the adjustment of the carrying volume of area 1 and/or the carrying volume of area 4, modifying the position of the characteristic point to bring the position of the characteristic point closer to the target position; - the volume of the mobile phase injected per cycle being maintained greater than, or equal to, a minimum limit and/or less than, or equal to, a maximum limit. - the determination, in a node of the system, of the history of a variable that is representative of the concentration of one or more species contained in the mixture to be separated; - the detection on said history of a single characteristic point in the portion of the history corresponding to area 1, area 4 and the interface between these two areas; - the comparison of the position of the characteristic point against a target position; - the adjustment of the carrying volume of area 1 and/or the carrying volume of area 4, modifying the position of the characteristic point to bring the position of the characteristic point closer to the target position; - the volume of the mobile phase injected per cycle being maintained greater than, or equal to, a minimum limit and/or less than, or equal to, a maximum limit.