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.
Department of Pharmacology, Walter Reed Army Institute of Research, Washington, DC 20307.
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Marino
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Peggins
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Brewer
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