Design of Experiments for Capillary Electrophoretic Enantioresolution of Tamsulosin using Sulfated‐β‐Cyclodextrin as Chiral Selector

Abstract

A method of quickly determining tamsulosin enantiomers by capillary zone electrophoresis with a photodiode array detector was developed. Response surface methodologies based on three‐level, three‐variable designs such as Box‐Behnken design, central composite face‐centered, and central composite circumscribed design, were comparatively used for the optimization with respect to selector concentration, applied voltage, and column temperature. Statistical interpretation of the variables on different responses, such as resolution and migration time of the last isomer were performed. The optimum conditions of these variables were predicted by using a second‐order polynomial model, fitted to the results obtained by applying three designs. The response surface plots using three experimental designs revealed a separation optimum with 100 mM tris (hydroxymethyl) aminomethane buffered with phosphoric acid to pH=2.5, concentration of sulfated‐β‐cyclodextrin, 0.15% (W/V), column temperature 25°C, and applied voltage of 25 kV. The significance of the statistical designs was confirmed by the generally good agreement obtained between predicted responses and actual experimental data. We have concluded that experimental designs offer a rapid means of optimizing several variables, and provide an efficient test for the robustness of the analytical method.

Keywords:

• Tamsulosin
• Response surface methodology
• Capillary electrophoresis
• Chiral separation
• Sulfated‐β
• ‐cyclodextrin
• Experimental design

Acknowledgments

The financial support from the NSFC‐KOSEF Scientific Cooperation Program, Program for New Century Talents of University in Henan Province, and Program for Backbone Teacher in Henan Province are acknowledged.