Development of an Intelligent Heart-Cut Liquid Chromatography System for Chiral Analysis of Chemical Processes

Multi-dimensional HPLC techniques enable researchers to monitor multiple essential and sometimes, critical quality attributes (CQAs) in parallel. A unique three-column, four-dimension liquid chromatography system employing a two-loop heart-cut strategy is reported. The system is capable of re-circulating effluents from each dimension through a single detector and performing heart-cut operations using a programmable ten-port, two-position heart-cut valve. The first dimension of analysis measures peak ratios of products to reagents while the second dimension offers peak purity of the heart-cut material. The third dimension uses a chiral column to measure the enantiomeric excess (ee) of the chiral analyte and the effluent from the third dimension is re-analyzed via a fourth dimension to determine if any loss of chirality has occurred resulting from the analytical method itself. Performance of the setup was evaluated using the synthesis of Warfarin as a model chemical process.