Quantification of the individual enantiomer plasma concentrations of the candidate antimalarial agent N4-[2,6-dimethoxy-4-methyl-5-[(3-trifluoromethyl)phenoxy]-8-quinolinyl] - 1,4-pentanediamine (WR 238,605).
A high-performance liquid chromatographic method was developed to quantitate the plasma concentrations of the individual enantiomers of a candidate 8-aminoquinoline antimalarial agent WR 238,605 (I). The method employed one-step liquid extraction of a 0.5-ml plasma sample followed by direct injection of the extract through a chiral column and detection by fluorescence. Quantification was achieved using an internal standard. The limit of quantification was 10 ng/ml for each enantiomer. The method is sufficiently sensitive to quantitate the plasma concentrations of both enantiomers for 30 days following a single oral dose of 400 mg of the antimalarial agent administered as the racemic succinate salt to healthy human male volunteers. In nearly all samples taken 12 h to 30 days post-dose from three subjects, the difference in the plasma concentrations of the two enantiomers is less than 10%.
Karle
J M
JM
Department of Pharmacology, Walter Reed Army Institute of Research, Washington, DC 20307, USA.
Olmeda
R
R
Freeman
S G
SG
Schroeder
A C
AC
D000293:Adolescent; D000328:Adult; D000634:Aminoquinolines / Q000097:blood*; D000962:Antimalarials / Q000097:blood*; D001682:Biological Availability; D006801:Humans; D008297:Male; D013237:Stereoisomerism
D000634:Aminoquinolines; D000962:Antimalarials; C055852:tafenoquine