Linked Life Data

18980865

Source:http://linkedlifedata.com/resource/pubmed/id/18980865

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2008-11-25
pubmed:abstractText
A bioanalytical method for the analysis of artesunate (ARS) and its metabolite dihydroartemisinin (DHA) in human plasma using protein precipitation and liquid chromatography coupled to positive tandem mass spectroscopy was developed. The method was validated according to published US FDA-guidelines and showed excellent performance. However, when it was applied to clinical pharmacokinetic studies in malaria, variable degradation of the artemisinins introduced an unacceptable large source of error, rendering the assay useless. Haemolytic products related to sample collection and malaria infection degraded the compounds. Addition of organic solvents during sample processing and even low volume addition of the internal standard in an organic solvent caused degradation. A solid phase extraction method avoiding organic solvents eliminated problems arising from haemolysis induced degradation. Plasma esterases mediated only approximately 20% of ex vivo hydrolysis of ARS into DHA. There are multiple sources of major preventable error in measuring ARS and DHA in plasma samples from clinical trials. These various pitfalls have undoubtedly contributed to the large inter-subject variation in plasma concentration profiles and derived pharmacokinetic parameters for these important antimalarial drugs.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1570-0232
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
876
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
54-60
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Major pitfalls in the measurement of artemisinin derivatives in plasma in clinical studies.
pubmed:affiliation
Faculty of Tropical Medicine, Mahidol University, Bangkok 10400, Thailand. niklas@tropmedres.ac
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural, Validation Studies