Quantification of dihydroartemisinin, artesunate and artemisinin in human blood: overcoming the technical challenge of protecting the peroxide bridge
| Autor: | Niklas Lindegardh, Janhom Pattayaso, Nicholas J. White, Pratap Singhasivanon, Benjamas Kamanikom, Nicholas P. J. Day, Warunee Hanpithakpong |
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| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
Male
Erythrocytes Metabolite medicine.medical_treatment Clinical Biochemistry Dihydroartemisinin Artesunate Pharmacology Mass Spectrometry Analytical Chemistry chemistry.chemical_compound Antimalarials Hemoglobins Drug Stability medicine Humans Ferrous Compounds General Pharmacology Toxicology and Pharmaceutics Artemisinin Potassium dichromate Whole blood Chemistry Reproducibility of Results General Medicine Artemisinins Deferoxamine Medical Laboratory Technology Hemoglobin medicine.drug Chromatography Liquid |
| Zdroj: | Bioanalysis. 3(14) |
| ISSN: | 1757-6199 1757-6180 |
| Popis: | 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 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. |
| Databáze: | OpenAIRE |
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