Identification of impurities in artemisinin, their behavior in high performance liquid chromatography and implications for the quality of derived anti-malarial drugs

Abstract

Previous work [1] on the HPLC analysis of artemisinin tentatively identified the two impurities present above trace levels. This identification was based on LC-MS results and NMR of impurities isolated from artemisinin. In this work the impurities have been synthesized allowing verification of their identity by LC-MS. It is found that the previously suggested elution order is incorrect. A determination of relative response factors strongly impacts suggested limits on impurity levels and explains the erroneous peak assignment. The fates of the identified impurities are explored in the transformation of artemisinin to its derivative active pharmaceutical ingredients. A survey of a wide variety of artemisinin samples isolated from different geographical regions, different growing seasons, different plant backgrounds and using different extraction and purification approaches showed that artemisinin has sufficient purity for its intended use as a raw material for anti-malarial drug products.