Quantification of dihydroartemisinin, artesunate and artemisinin in human blood: Overcoming the technical challenge of protecting the peroxide bridge
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 v...
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th-mahidol.115252018-05-03T15:41:58Z Quantification of dihydroartemisinin, artesunate and artemisinin in human blood: Overcoming the technical challenge of protecting the peroxide bridge Niklas Lindegardh Warunee Hanpithakpong Benjamas Kamanikom Janhom Pattayaso Pratap Singhasivanon Nicholas J. White Nicholas P J Day Mahidol University Nuffield Department of Clinical Medicine Biochemistry, Genetics and Molecular Biology Chemistry Health Professions Pharmacology, Toxicology and Pharmaceutics 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. © 2011 Future Science Ltd. 2018-05-03T08:01:56Z 2018-05-03T08:01:56Z 2011-07-01 Article Bioanalysis. Vol.3, No.14 (2011), 1613-1624 10.4155/bio.11.158 17576199 17576180 2-s2.0-79960553046 https://repository.li.mahidol.ac.th/handle/123456789/11525 Mahidol University SCOPUS https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=79960553046&origin=inward |
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Biochemistry, Genetics and Molecular Biology Chemistry Health Professions Pharmacology, Toxicology and Pharmaceutics Niklas Lindegardh Warunee Hanpithakpong Benjamas Kamanikom Janhom Pattayaso Pratap Singhasivanon Nicholas J. White Nicholas P J Day Quantification of dihydroartemisinin, artesunate and artemisinin in human blood: Overcoming the technical challenge of protecting the peroxide bridge |
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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 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. © 2011 Future Science Ltd. |
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Mahidol University |
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Mahidol University Niklas Lindegardh Warunee Hanpithakpong Benjamas Kamanikom Janhom Pattayaso Pratap Singhasivanon Nicholas J. White Nicholas P J Day |
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Article |
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Niklas Lindegardh Warunee Hanpithakpong Benjamas Kamanikom Janhom Pattayaso Pratap Singhasivanon Nicholas J. White Nicholas P J Day |
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Niklas Lindegardh |
title |
Quantification of dihydroartemisinin, artesunate and artemisinin in human blood: Overcoming the technical challenge of protecting the peroxide bridge |
title_short |
Quantification of dihydroartemisinin, artesunate and artemisinin in human blood: Overcoming the technical challenge of protecting the peroxide bridge |
title_full |
Quantification of dihydroartemisinin, artesunate and artemisinin in human blood: Overcoming the technical challenge of protecting the peroxide bridge |
title_fullStr |
Quantification of dihydroartemisinin, artesunate and artemisinin in human blood: Overcoming the technical challenge of protecting the peroxide bridge |
title_full_unstemmed |
Quantification of dihydroartemisinin, artesunate and artemisinin in human blood: Overcoming the technical challenge of protecting the peroxide bridge |
title_sort |
quantification of dihydroartemisinin, artesunate and artemisinin in human blood: overcoming the technical challenge of protecting the peroxide bridge |
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2018 |
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https://repository.li.mahidol.ac.th/handle/123456789/11525 |
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