Support of Study Entitled, 'Metabolism and Pharmacokinetics of Dihydroartemisinin' and 'In Vitro and In Vivo Metabolism of Sodium Artelinate and DQHS in Rats and Humans'.

Abstract

Identification of the metabolites of DQHS and other artemisinin analogues has been problematic because of the unavailability of standards of the putative metabolites. The following report presents our attempts to circumvent this problem through a combination of mass spectrometry and derivatization of DQHS. The metabolism of dinydroqinghaosu (DQHS) (dihydroartemisinin) in rat liver microsomes and the isolated perfused rat liver was studied. The metabolites were identified by high performance liquid chromatography/thermospray (TSP) mass spectrometry. The metabolism of DQHS was found to involve C-hydroxylation at the 2-, 3-, 9-, or 14-position. Deoxygenation of the endoperoxide function together with C-hydroxylation gave rise to different isomers of hydroxy deoxydihydroqinghaosu (hydroxy deoxyDQHS), the prevalent metabolites of DQHS. DQHS also apparently underwent enzymatic oxidation to isomers of both hydroxy deoxyqinghaosu and dihydroxy deoxyQHS.

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Document Details

Document Type
Technical Report
Publication Date
Oct 01, 1996
Accession Number
ADA319697

Entities

People

  • Olutosin R. Idowu

Tags

DTIC Thesaurus Topics

  • Alcohols
  • Amino Acids
  • Antimalarials
  • Blood
  • Cellular Structures
  • Chemistry
  • Chromatography
  • Detection
  • Liquid Chromatography
  • Malaria
  • Mass Spectra
  • Mass Spectrometry
  • Metabolism
  • Microsomes
  • Molecules
  • Spectrometry
  • Standards

Fields of Study

  • Chemistry

Readers

  • Organic Chemistry
  • Parasitology and Pharmacology of Malaria.
  • Toxicology/Environmental Toxicology