High-performance liquid chromatographic method for the determination of a candidate 8-aminoquinoline antimalarial drug (WR 242511) using oxidative electrochemical detection.
WR 242511 (or I) is a new compound of the 8-aminoquinoline class designed to replace primaquine for the treatment of malaria. In order to perform preclinical and clinical testing, an assay was needed to determine drug levels in plasma samples. A simple and reliable reversed-phase high-performance liquid chromatographic (HPLC) method for the measurement of I in plasma using oxidative electrochemical detection is described. A 250-microliters plasma sample containing WR 256408 (or II) as internal standard was extracted with tert.-butyl methyl ether-2-propanol. A 25-microliters aliquot of the extractant was used for HPLC analysis. The mobile phase was 50:50 acetonitrile-sodium acetate (50 mM, pH 6) with 1 mM EDTA. Compounds I and II were separated within 10 min. The limit of detection for I was 10 ng/ml (plasma) with a recovery around 72%. The method was validated in a dog experiment where levels were followed for 48 h. The method is sensitive and robust and can be used for routine drug analysis during pharmacokinetic studies.
Marino
M T
MT
Department of Pharmacology, Walter Reed Army Institute of Research, Washington, DC 20307.
Peggins
J O
JO
Brewer
T G
TG
D000818:Animals; D000962:Antimalarials / Q000097:blood* / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D004563:Electrochemistry; D006801:Humans; D007275:Injections, Intravenous; D010084:Oxidation-Reduction; D010865:Pilot Projects; D011319:Primaquine / Q000031:analogs & derivatives* / Q000097:blood / Q000493:pharmacokinetics
D000962:Antimalarials; C068820:WR 242511; D011319:Primaquine