Selectivity optimization in liquid chromatography using the thermally tuned tandem column T(3)C concept

In this thesis we describe a novel "thermally tuned tandem column (T3C)" concept for the optimization of selectivity in liquid chromatography by continuous adjustment of the stationary phase. Two columns with distinctly different chromatographic selectivities are serially coupled and independently temperature controlled. Selectivity is "tuned" by adjusting the individual temperatures of the two columns. The effect of changing column temperature is quite analogous to changing the relative column lengths; thereby altering the relative and absolute contribution each column makes to the overall retention time in T3C. We have developed a simplified useful model, which characterizes retention and selectivity for the T3C system as a function of the two column temperatures. The model is in good agreement with the experimental results. We also describe a simple computer-assisted optimization strategy based on the window diagram method, which facilitates the optimization of the T 3C system with only four or five initial runs.; T3C approach has been successfully used to separate complex environmental, biological and pharmaceutical samples including triazine herbicides, carbamate pesticides, barbiturates, PTH-amino acids and antihistamines. The approach usually provides superior separations as compared to the separation on a single column. In addition, the optimized separations on T3C are generally better than those achieved by mobile phase optimization on a single column. The combination of superior selectivity and high flow rate allows the baseline separation of complex mixtures in just a few minutes. We believe T3C approach provides a powerful and efficient method to solving difficult separation problems in liquid chromatography.