title: A liquid chromatographic-tandem mass spectrometric method for determination of artemether and its metabolite dihydroartemisinin in human plasma.
abstract: BACKGROUND
  Artemether-lumefantrine is the most widely recommended artemisinin-based combination treatment for falciparum malaria. Quantification of artemether and its metabolite dihydroartemisinin in biological matrices has traditionally been difficult, with sensitivity being an issue.
  
  
  RESULTS
  A high-throughput bioanalytical method for the analysis of artemether and its metabolite dihydroartemisinin in human plasma using solid-phase extraction in the 96-well plate format and liquid chromatography coupled to positive ion mode tandem mass spectroscopy has been developed and validated according to US FDA guidelines. The method uses 50 µl plasma and covers the calibration range 1.43-500 ng/ml with a limit of detection at 0.36 ng/ml.
  
  
  CONCLUSIONS
  The developed liquid chromatography-tandem mass spectrometry assay is more sensitive than all previous methods despite using a lower plasma volume (50 µl) and is highly suitable for clinical studies where plasma volumes are limited, such as pediatric trials.
authors.affiliation: Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
authors.forename: Warunee
authors.initials: W
authors.lastname: Hanpithakpong
authors.forename: Benjamas
authors.initials: B
authors.lastname: Kamanikom
authors.forename: Pratap
authors.initials: P
authors.lastname: Singhasivanon
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: White
authors.forename: Nicholas Pj
authors.initials: NP
authors.lastname: Day
authors.forename: Niklas
authors.initials: N
authors.lastname: Lindegardh
mesh_terms: D000962:Antimalarials / Q000097:blood*; D000077549:Artemether; D037621:Artemisinins / Q000097:blood*; D002138:Calibration; D002853:Chromatography, Liquid; D004359:Drug Therapy, Combination; D004983:Ethanolamines / Q000378:metabolism; D005449:Fluorenes / Q000378:metabolism; D057166:High-Throughput Screening Assays; D006801:Humans; D000078102:Lumefantrine; D016778:Malaria, Falciparum / Q000188:drug therapy*; D015203:Reproducibility of Results; D052616:Solid Phase Extraction; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry
chemical_list: D000962:Antimalarials; D037621:Artemisinins; D004983:Ethanolamines; D005449:Fluorenes; C039060:artenimol; D000077549:Artemether; D000078102:Lumefantrine