A new concept is developed for improving the cycle time and the sample throughput in preparative liquid chromatography. In this flip—flop elution procedure, the direction of the mobile phase flow is reversed just after the compound of interest has been collected. The next sample injection is made at the other end of the column to the previous injection as the flow direction has been changed after a certain delay time. This time is determined in such a way that the compound of interest begins to elute (and can be collected) just after the end of the backflush peak of strongly retained components from the previous injection. In this way, no time is lost in separating and eluting the most strongly retained impurities. General expressions for the delay time and the cycle time (time between two consecutive injections) are given for diluted (Gaussian) as well as severely overloaded peaks. Similar expressions are also given for an optimized version of the normal elution procedure in which the direction of the flow of mobile phase remains unchanged. It is shown that the flip—flop operation gives a shorter cycle time than the optimized normal elution process when the time of the end of collection of the compound of interest is less than half the retention time of the last compound in the chromatogram. An experimental demonstration of the flip—flop elution concept is shown. It is emphasized that this concept can be extended to other separation techniques and to analytical separations where quantitative information is searched for only a fraction of the number of sample components.
