Rapid and sensitive quantitative analysis of the new antimalarial N4-[2,6-dimethoxy-4-methyl-5-[(3-trifluoromethyl)phenoxy]-8- quinolinyl]-1,4-pentanediamine in plasma by liquid chromatography and electrochemical detection.
A rapid, sensitive and simple method was developed for the quantitation of the plasma concentration of N4-[2,6-dimethoxy-4-methyl-5-[(3-trifluoromethyl)phenoxy]-8- quinolinyl]-1,4-pentanediamine, a new antimalarial active against Plasmodium vivax. N4-(5-Hexoxy-6-methoxy-4-methyl-8-quinolinyl)-1,4- pentanediamine diphosphate, a similar 8-aminoquinoline, was used as an internal standard. The method involves sample clean-up by a prepacked cyano solid-phase column followed by reversed-phase liquid chromatography and oxidative electrochemical detection at +0.95 V. The assay has been validated to 5 ng/ml of plasma and is sensitive to 1 ng/ml of plasma. The results of a pilot study assessing the relative oral bioavailability of two different salt forms of the new antimalarial in dogs show the usefulness of the method for animal and human pharmacokinetic studies.
Karle
J M
JM
Department of Pharmacology, Walter Reed Army Institute of Research, Washington, DC 20307-5100.
Olmeda
R
R
D000634:Aminoquinolines / Q000097:blood* / Q000493:pharmacokinetics; D000818:Animals; D000962:Antimalarials / Q000097:blood* / Q000493:pharmacokinetics; D001682:Biological Availability; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D004563:Electrochemistry; D005260:Female; D006801:Humans; D013056:Spectrophotometry, Ultraviolet
D000634:Aminoquinolines; D000962:Antimalarials; C055852:tafenoquine