SIMPLIFIED LIQUID-CHROMATOGRAPHY ASSAY FOR THE QUANTITATION OF HALOFANTRINE AND DESBUTYLHALOFANTRINE IN PLASMA AND IDENTIFICATION OF A DEGRADATION PRODUCT OF DESBUTYLHALOFANTRINE FORMED UNDER ALKALINE CONDITIONS

The development of a new and simplified, validated LC assay for the quantitation of halofantrine and desbutylhalofantrine in plasma is described. The methodology employs an inexpensive, rapid and simple liquid-liquid extraction procedure in combination with previously reported chromatographic conditions. The method has been employed to study aspects of the pharmacokinetics of orally administered halofantrine in beagle dogs and some preliminary data are presented. During development of the extraction procedure, degradation of desbutylhalofantrine was observed under non-acidic conditions in the extraction solvent (tert-butyl methyl ether) and we also report the structural elucidation of the breakdown product and the conditions required to avoid this degradation.