An improved high-performance liquid chromatography process for the large-scale production of paclitaxel

摘要

The purification of crude (60.89% pure) paclitaxel was developed for high purity and yield. Several solvent systems, including methanol (MeOH), acetone, tetrahydrofurane, n-hexane, and water, were evaluated for precipitation efficiency. The best results were obtained using a mixture of MeOH and water, which was very effective at removing polar impurities, yielding a precipitate with 90.87% purity. Paclitaxel was purified from crude (60.89% pure) by two different high-performance liquid chromatography (HPLC) systems employing silica and octadecylsilane (ODS) stationary phases, respectively. Column lengths, sample injection volumes, and solvent ratios were optimized for both systems. Optimal ODS-HPLC performance was observed with a 90-cm column and 65-70% MeOH in water to give 99.1% purity. The silica-HPLC performed best with a 60-cm column with 1.5-1.8% MeOH in dichloromethane to give 89.5% purity. The combination of these techniques resulted in 99.5% pure paclitaxel obtained in over 90% yield. The optimized process was scalable to clinical production levels, and boasts several economic advantages such as low production cost from the reuse of solvents, consistent purity and yield, high sample loading, and process automation.