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A robust and validated ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method has been developed for the simultaneous determination of buagafuran and one metabolite (M1) in human plasma. The two analytes were extracted from plasma samples using tert-butyl methyl ether after addition of the internal standard and chromatographed on an Acquity UPLC BEH C18 column (2.1mm×50mm, 1.7μm) thermostatted at 35°C with methanol-water (75:25, v/v) as the mobile phase at an isocratic flow rate of 0.4mL/min. The detection was performed on an API 5500 mass spectrometer coupled with electrospray ionization (ESI) source in positive mode. The multiple reactions monitoring (MRM) transitions of m/z 245.2→109.1 and m/z 279.1→243.1 were used to quantify buagafuran and M1, respectively. The assay was validated over the concentration range of 0.5-200ng/mL for the two analytes. Precision and accuracy are in accordance with the generally accepted criteria for bioanalytical methods. The extraction recovery and the matrix effect were investigated. This method was successfully applied to support a clinical study where multiple oral doses were administrated to healthy Chinese volunteers to investigate the pharmacokinetics, safety and tolerability of buagafuran., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Multiple dose pharmacokinetics of artemether and dihydroartemisinin were investigated in chinese patients treated for malaria. They received over 2 days either 4 x 80 mg artemether orally (n = 48) or 4 x 80-480 mg co-artemether (n = 40), a combination of artemether and lumefantrine (benflumetol). Lag time = 0.48 h (mean), Cmax after first dose = 157 ng/ml, t(max) = 1.73 h and elimination half-life = 1.16 h. The lag and absorption times were 0.5 h longer for co-artemether compared with artemether. Dihydroartemisinin paralleled artemether pharmacokinetics. Artemether Cmax after the last dose was one-third of the Cmax after the first dose while, inversely, dihydroartemisinin Cmax increased over time. We suggest that auto-induction of gut mucosa enzymes and/or liver enzymes causes a time-dependent increase in first-pass metabolisation of artemether.