The effect of O-methylated flavonoids and other co-metabolites on the crystallization and purification of artemisinin

• Co-metabolites negatively impacting crystallization of artemisinin were identified.
• Flavonoid artemetin has strongest impact on crystallization of artemisinin.
• Elevated levels of artemetin were found in the problematic East African biomass.

Methoxylated flavonoids casticin, artemetin and retusin were identified as putative causative factors for low crystallization yields of artemisinin from extracts. Comparative profiling of biomass grown in different countries found elevated levels (∼60% higher) of artemetin in the East African biomass, which also demonstrates poor crystallization yields. The single compound and the combined doping experiments at 0, 25 and 50 μg mL−1 doping levels showed that artemetin (at 50 μg mL−1) caused a reduction in the amount of artemisinin crystallized by ca. 60%. A combination of the three flavonoids at 50 μg mL−1 almost completely inhibited crystallization, reducing the yield by 98%. Treatment of extracts by adsorbents efficiently resolves the problem of low crystallization yield.