Journal
BIOANALYSIS
Volume 3, Issue 14, Pages 1613-1624Publisher
FUTURE SCI LTD
DOI: 10.4155/BIO.11.158
Keywords
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Funding
- Wellcome Trust of Great Britain [077166/Z/05/Z]
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Background: Quantification of artemisinin (ARN) and its derivatives in whole blood has hitherto been thought impossible. Results: A LC-MS/MS method for the ana-lysis of artesunate (ARS), its metabolite dihydroartemisinin (DHA) and artemisinin in human whole blood has been developed and successfully validated. The method includes stabilization of the blood matrix at the time of collection and at the time of ana-lysis. Addition of potassium dichromate to the blood samples deactivated the Fe2+ core in hemoglobin, while deferoxamine chelated Fe3+ and prevented back conversion into Fe2+. A pilot study showed that the blood: plasma ratio for ARS and DHA is approximately 0.75, indicating a significantly lower uptake in red blood cells than had previously been estimated using radiolabeled drug methodology. Conclusions: The developed LC-MS/MS assay is the first method available for quantification of ARN and its derivatives in blood and opens up new possibilities of studying these drugs inside infected red blood cells.
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