Artemisinin (ART) is a sesquiterpene lactone and a popular malaria drug with potential anticancer properties. In this work, LC/TOF/MS, was used to investigate the reaction of ART with DNA bases. ART-deoxyadenosine and ART-deoxycytidine interactions, were studied in the presence of iron II ions. ART-deoxyadenosine and ART-deoxycytidine reaction mixtures gave chromatographic signatures that remained fairly unchanged at room temperature but grew after incubation at 37 °C. The change in temperature from room temperature to 37 °C was the main driver of adduct formation in these reactions. ART was found to react with Fe(II) ions as observed from several new chromatographic peaks. ART-deoxyadenosine as well as ART-deoxycytidine in the presence of Fe(II) ions resulted in formation of new chromatographic signatures of adducts consisting of DNA bases and ART. It was clear that addition of iron (II) to DNA base-ART mixtures gave rise to new reaction products mediated by a different reaction mechanism. Studies of ART reactions with DNA in vitro is key in elucidating elusive mechanism of this drug.

Artemisinin (ART) is a sesquiterpene lactone and a popular malaria drug used in many parts of the world. Artesunate (ARTS) is a semi-synthetic derivative of ART with improved pharmacokinetic properties. However, the half-life of ARTS is less than an hour in vivo. The analysis of this drug in vitro in different solvent systems using LC-MS/TOF showed a solvent-driven breakdown. ARTS breakdown formed several derivatives, including dihydroartemisinin (DHA), artemether (ARTM) and DHA-dimer among others, at different rates in different solvent composition systems. The change in temperature from room temperature to physiological temperature (37 °C) was found to enhance the rate of the ARTS breakdown. In methanol, ARTS mainly formed ARTM with a chromatographic peak decrease of about 3.13%, while methanol and water (90:10) v/v mainly gave rise to DHA and ARTM with about an 80% chromatographic peak decrease. On the other hand, ARTS in methanol and ammonium acetate (85:15) v/v formed DHA, ARTM, DHA-dimer and other reaction peaks with about a 97% peak decrease and the formation of an orange solution pointing to a molecular re-arrangement reaction. These results have an important bearing on research on the analysis of artemisinin drugs conducted on these common solvents.