Purification of homoharringtonine and removal of residual solvents by spray drying

Abstract

Homoharringtonine was purified from Cephalotaxus koreana by a combination of extraction, synthetic adsorbent treatment, low-pressure chromatography, and high performance liquid chromatography (HPLC). A crude extract was obtained by methanol extraction of biomass, followed by liquid-liquid extraction using chloroform. The waxy compounds were efficiently removed by adsorbent (active clay P-1) treatment. The extract was purified to greater than 52% with an 86.4% step yield by silica gel low-pressure chromatography. High performance liquid chromatography steps, which were composed of an HPLC step with silica column and an HPLC step with ODS column, were applied to give 98% purity with high yield. Amorphous homoharringtonine, with a fine particle size, was simply made by dissolving homoharringtonine in methylene chloride/methanol (98/2, v/v), followed by spray drying. Residual solvents, methylene chloride and methanol, could be reduced to 250 ppm and 1,160 ppm by spray drying and successive drying in a vacuum oven.