BACKGROUND: Quantification of artemisinin (ARN) and its derivatives in whole blood has hitherto been thought impossible. RESULTS: A LC-MS/MS method for the analysis 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 analysis. Addition of potassium dichromate to the blood samples deactivated the Fe(2+) core in hemoglobin, while deferoxamine chelated Fe(3+) and prevented back conversion into Fe(2+). 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.
BACKGROUND: Quantification of artemisinin (ARN) and its derivatives in whole blood has hitherto been thought impossible. RESULTS: A LC-MS/MS method for the analysis 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 analysis. Addition of potassium dichromate to the blood samples deactivated the Fe(2+) core in hemoglobin, while deferoxamine chelated Fe(3+) and prevented back conversion into Fe(2+). 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.
Authors: Daniel Blessborn; Karl Sköld; David Zeeberg; Karnrawee Kaewkhao; Olof Sköld; Martin Ahnoff Journal: Bioanalysis Date: 2013-01 Impact factor: 2.681
Authors: S G Zaloumis; J Tarning; S Krishna; R N Price; N J White; T M E Davis; J M McCaw; P Olliaro; R J Maude; P Kremsner; A Dondorp; M Gomes; K Barnes; J A Simpson Journal: CPT Pharmacometrics Syst Pharmacol Date: 2014-11-05
Authors: Palang Chotsiri; Thanaporn Wattanakul; Richard M Hoglund; Borimas Hanboonkunupakarn; Sasithon Pukrittayakamee; Daniel Blessborn; Podjanee Jittamala; Nicholas J White; Nicholas P J Day; Joel Tarning Journal: Br J Clin Pharmacol Date: 2017-08-16 Impact factor: 4.335
Authors: I C E Hendriksen; G Mtove; A Kent; S Gesase; H Reyburn; M M Lemnge; N Lindegardh; N P J Day; L von Seidlein; N J White; A M Dondorp; J Tarning Journal: Clin Pharmacol Ther Date: 2013-02-08 Impact factor: 6.875
Authors: Susan A Charman; Alice Andreu; Helena Barker; Scott Blundell; Anna Campbell; Michael Campbell; Gong Chen; Francis C K Chiu; Elly Crighton; Kasiram Katneni; Julia Morizzi; Rahul Patil; Thao Pham; Eileen Ryan; Jessica Saunders; David M Shackleford; Karen L White; Lisa Almond; Maurice Dickins; Dennis A Smith; Joerg J Moehrle; Jeremy N Burrows; Nada Abla Journal: Malar J Date: 2020-01-02 Impact factor: 2.979