A combined organic solvent/flow double-gradient mode in HPLC using a monolithic column is established as a new approach to determination of four saponins in Sanqi Chinese Medicinal Granules. The correlation between content of acetonitrile and lg k, flow and lg k, by which suitable k values of notoginsenosid R₁, ginsenoside Rg₁ and Re were calculated. The resolution of test analytes were used as a criterion, the good separation mode 1 and 2 of R₁, Rg₁ and Re were obtained. In developing the separation ginsenoside Rb₁ the effect on the changes of acetonitrile content and flow with time, the resolution of the critical pair (impurities 1, 2 and Rb₁) were chosen as a criterion, the optimal modes of separation on R₁, Rg₁, Re and Rb₁ have been obtained. Chromatographic optimization function (COF) values were used as objective functions, the results show that model 2 is better optimized. The optimized method was validated and applied for quantitative analysis of four saponins of Sanqi Chinese Medicinal Granules. Duration of chromatographic run was 20 min. The results indicate that the method is accurate, feasible, and fast.

Key words: organic solvent/flow double-gradient, monolithic column, HPLC, sanqi chinese medicinal granules