Spectrophotometric and ESI-MS/HPLC studies reveal a common mechanism for the reaction of various artemisinin analogues with hemin

The reaction of hemin with three well known artemisinin analogues, namely dihydroartemisinin, artemether and artesunate, was independently analysed by visible spectrophotometry and by ESI-MS/HPLC. A very similar reaction pathway emerges for all these compounds that matches closely the reaction profile previously described for artemisinin. In the course of the reaction characteristic isomeric 1:1 drug–hemin adducts are formed as in the case of artemisinin; eventual disruption of the porphyrin ring takes place in all cases, most likely through oxidative degradation.