Development of a Solvent−Saving Direct−Pumping Recycle Chromatographic System and Its Application to the Separation of Deuterated Benzenes in Liquid Chromatography

When a difficult separation cannot be accomplished by changing the column and mobile phase conditions, two alternate methods are available. The most common approach is to increase the column length with identical packing material, and the second approach is to recycle the sample through the column. However, the former approach might lead to a limitation to the separation efficiency due to an increased inlet pressure whereas in the latter case, the dead volume in the recycle lines causes band broadening and peaks can only be recycled until they begin to overlap. Thus, the recycle technique has been limited to preparative chromatography where larger diameter columns are employed [1−7]. In preparative chromatography, the recycle technique is well−known as a useful tool to improve enantioseparation, production rate and recovery yield. Trone et al. [6] have developed a peak trapping recycle chromatography (RC) system and optimized it for peak purity assessment of active pharmaceutical ingredients. After being analyzed using a reversed phase analytical column, peaks of interest were trapped and were subsequently introduced to an RC system. They have achieved over 227,000 theoretical plates for some compounds. Zhang and McConnell [7] have described the development of a novel column−switching technique called “simulated moving columns” (SMC) to quickly achieve complete chiral resolution on columns with limited enantioselectivity. SMC helped to achieve chiral resolution by virtually multiplying the column length, thus enhancing separation efficiency and resolution, without increasing backpressure. The results clearly indicated that SMC eliminated the significant band broadening that was inevitable in the closed−loop reOriginal