Chiral separations using packed capillary liquid chromatography

Reduction of the internal diameter of the column used for the separation of enantiomers by liquid chromatography to microcolumn dimensions (0.1‐0.5 mm i.d.) offers significant advantages to the technique, such as low eluent consumption, reduced packing material needs which ensures column‐to‐column reproducibility and lower column costs, and high efficiencies, among others. The present report documents studies conducted in the preparation of highly efficient microcolumns for chiral separations using Chiracel OD stationary phase (3,5‐dimethylphenylcarbamate derivative of cellulose). The resolution, efficiency, and peak asymmetry values obtained using microcolumns were significantly better when compared to a conventional size column (4.6 mm i.d.) of the same length (25 cm). These results may be explained by the more efficient column packing process when using fused silica tubing of narrow diameter as column material. The use of long (80 cm) microcolumns yielded increases in enantiomer resolution of 200–300%. Operation of the long microcolumns at high linear velocities resulted in resolution increases over conventional columns without a decrease in analysis time. In addition to much improved column performance, miniaturization of chiral separation systems has a significant economic impact. Since operating flow rates are 5 μL min−1 compared to 1–2 mL min−1 for conventional columns, a significant savings in the cost of solvents and solvent disposal can be realized by using the microcolumn technology. In addition, the small amount of packing material required to prepare a microcolumn significantly reduces column costs.