Major pitfalls in the measurement of artemisinin derivatives in plasma in clinical studies

Pharmacokinetics of Artesunate Alone and in Combination with Sulfadoxine/Pyrimethamine in Healthy Sudanese Volunteers

“…Also, the protein binding of AS and DHA is relatively high (75% and 93% for AS and DHA, respectively). 24,42 Because AS and DHA are non-restrictive clearance drugs, 43 any change in the level of protein binding is unlikely to produce significant changes in the clearance of AS or DHA because the clearance of these drugs is dependent on hepatic blood flow and independent on the protein binding capacity of such drugs. This finding could presumably explain the unaltered clearance levels of AS (after AS alone) and DHA (after AS alone and combined therapy) in healthy men and women in the present study.…”

“…[14][15][16][17][18][19][20] Currently, the suitable method for quantification of these compounds in plasma is liquid chromatography coupled with mass spectrometry detection (LC-Ms or LC-MS/MS) with quantification limits of approximately 1 ng/mL using only 50-μL plasma sample volumes. [21][22][23][24][25] However, some of the problems encountered the latter bioanalytical methods include lack of appropriate stable isotope-labeled AS and DHA internal standards, in addition to expensive solid phase extraction cartridges that most commonly used for extraction of AS and DHA from biological samples.…”

Artemisinin Resistance inPlasmodium falciparumMalaria

“…Artesunate and dihydroartemisinin concentrations at the Cambodian site were multiplied by 1.09 to adjust for the different anticoagulants used at the Thai site. 15 We report the observed maximum plasma concentrations of artesunate and dihydroartemisinin and the observed times to the maximum concentration.…”

“…In Pailin, the samples were collected on ice in prechilled fluoride-oxalate tubes. After methodologic investigations, 15 the tubes were changed to prechilled lithium-heparin tubes for the Thailand study. Samples were centrifuged at 4°C and stored in liquid nitrogen until analysis.…”

Pharmacokinetic modelling of the anti-malarial drug artesunate and its active metabolite dihydroartemisinin

“…Samples were analysed to determine their ARS and DHA concentrations using tandem liquid chromatography-mass spectrometry (on a Thermo Fisher Quantum Access Triple Quad Mass Spectrometer) based on the assay described in Lindegardh et al [27]. (The individual samples were analysed only once but assay robustness was confirmed by a re-analysis of approximately 10% of all samples.…”