title: Analysis of the antimalarial drug halofantrine and its major metabolite N-desbutylhalofantrine in human plasma by high performance liquid chromatography.
abstract: The determination of halofantrine and its major metabolite N-desbutylhalofantrine in human plasma by reversed phase high-pressure liquid chromatography is described. The method involves protein precipitation of plasma samples by acetonitrile followed by basification with sodium hydroxide and subsequent liquid-liquid extraction using hexane-diethyl ether (1:1, v/v). The chromatographic separation was carried out on a C-18 column with a mobile phase consisting of methanol/0.05 M KH2PO4 (78:22, v/v) containing 55 mM perchloric acid. Chlorprothixen was used as internal standard. The relative standard deviations of intraday and interday precision for both compounds were less than 7%, the relative standard deviation of the accuracy did not exceed 7.1% at concentrations of 50 and 300 ng/ml. This method is simple, rapid, sensitive and cost effective and was applied to the determination of the pharmacokinetics of halofantrine and N-desbutylhalofantrine in two healthy male volunteers after an oral administration of 500 mg halofantrine. Moreover, the influence of the frequently consumed kolanut on the pharmacokinetics of halofantrine was investigated.
authors.affiliation: Department of Pharmaceutical Chemistry, School of Pharmacy, University of Jena, Philosophenweg 14, 07743 Jena, Germany.
authors.forename: Yetunde T
authors.initials: YT
authors.lastname: Kolade
authors.forename: Chinedum P
authors.initials: CP
authors.lastname: Babalola
authors.forename: Gerhard K E
authors.initials: GK
authors.lastname: Scriba
mesh_terms: D000962:Antimalarials / Q000032:analysis* / Q000737:chemistry; D002138:Calibration; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008956:Models, Chemical; D010616:Phenanthrenes / Q000032:analysis* / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D013678:Technology, Pharmaceutical / Q000379:methods*; D013997:Time Factors
chemical_list: D000962:Antimalarials; D010616:Phenanthrenes; C044961:1,3-dichloro-6-trifluoromethyl-9-phenanthryl-3-(n-butyl)aminopropanol; C023768:halofantrine