Analysis of hydrophobic amine antimalarials in biological fluids with the plastic ion-selective electrode

Abstract

Plastic ion-selective electrode analysis of the hydrophobic amine antimalarial mefloquine in blood samples was investigated. The direct electrode response in plasma samples provided poor drug sensitivity due to high mefloquine protein binding. The drug was analyzed in whole blood by initial extraction into ether as its trichloroacetate ion-pair. Mefloquine was monitored in whole blood extracts with the electrode to moderately low levels (to 0.4 microgram/ml). Rapid blood mefloquine level monitoring by this electrode was demonstrated in a bioavailability study. Mefloquine alkylation with various alkyl halides produced derivatives detectable by the electrode at much lower levels (up to two orders of magnitude) than the parent. A kinetic study of this alkylation reaction revealed that an alkyl amine base was necessary to scavenge the acid produced during reaction and to allow the reaction to go to completion. At room temperature, with benzyl bromide as the reagent, reaction was 99% complete in 30 min and mefloquine could be detected to approximately to 10(-8) M, a 100-fold improvement in sensitivity over electrode monitoring of underivatized mefloquine.