Comparison of counter-current chromatography and preparative high performance liquid chromatography applied to separating minor impurities in drug preparations

Abstract

Drug impurity profiling and identification are carried out along with the drug discovery process. Due to its inherent low concentration in drug products, the isolation and purification of impurities present a challenge to drug development processes. In our development of honokiol and quercetin as anticancer drug candidates, counter-current chromatography (CCC) and preparative HPLC were used for the impurity profiling and identification of honokiol and quercetin. Several performance parameters such as separation column volume, maximum sample loading, separation time, solvent consumption and sample throughput were investigated in order to compare the separation efficiency. We found that the sample loading capacity and therefore the throughput of preparative HPLC were not satisfactory, while CCC provided larger sample loading (especially for a sample with poor solubility), consumed less solvent and produced higher throughput than preparative HPLC. Six impurities of honokiol including one new compound were isolated in the present work.