SELECTIVE HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHIC DETERMINATION OF ARTESUNATE AND ALPHA-DIHYDROARTEMISININ AND BETA-DIHYDROARTEMISININ IN PATIENTS WITH FALCIPARUM-MALARIA

A novel solid-phase extraction and a robust high-performance liquid ch romatographic (HPLC) separation procedure for artesunate and alpha- an d beta-dihydroartemisinin, using post-column alkali decomposition and UV detection, is described. Extraction was performed with Bond-Elut Ph enyl solid-phase extraction cartridges and analysis by HPLC was carrie d out using a Waters Symmetry C-8 5-mu m 150 X 3.9 mm I.D. column. The mobile phase was 50% acetonitrile in 0.1 M acetate buffer (pH 4.8) de livered at a flow-rate of 0.7 ml/min. The column eluate was mixed with 1.2 M potassium hydroxide in 90% methanol delivered at 0.3 ml/min, in a 1-ml reaction coil at 69 degrees C, to form UV-absorbing chromophor es which were detected at 290 nm. The recovery of all analytes was gre ater than 80%. There was no significant difference in the peak-area ra tio of alpha- and beta-dihydroartemisinin in plasma. Preliminary pharm acokinetic data from six adult Vietnamese patients who received 120 mg of artesunate by intravenous injection for the treatment of acute fal ciparum malaria are presented. Despite limited data, the mean half-lif e of artesunate was approximately 3.5 min while that for dihydroartemi sinin was 34 min. These data confirm the relatively rapid clearance of both artesunate and its principal active metabolite, dihydroartemisin in.