An unexpected Griess reaction on the important anti-malarial drug primaquine and its application for drug determination

Abstract

Primaquine (PMQ), a well-known anti-malarial drug, is of increasing importance as people moving toward global malaria eradication. PMQ has serious side effects that it often causes acute hemolytic toxicity in people with glucose-6-phosphate dehydrogenase (G6PD) deficiency. The development of simple and reliable approaches for quantitative dose monitoring is thus becoming important during malarial treatment with PMQ. Herein, an unexpected Griess reaction on PMQ was systematically studied. The reaction happened between substituted aniline and a primaquine molecule in the presence of nitrite. Both experimental measurements and theoretic calculation showed that UV-vis absorption of the azo products varied because of different electron contributing effects of substituents. Based on the optimized conditions, a novel colorimetric method has been developed for PMQ determination with excellent sensitivity and selectivity. The detection limits for PMQ in water and synthetic urine samples were down to nanomolar range. More importantly, this method has been successfully used to quantify PMQ from human serum samples within clinically relevant concentration ranges.

Keywords: Anti-malarial primaquine; Drug colorimetric detection; Griess reaction; TD-DFT calculation.