Selective Detection of Chloroquine in Human Urine with Application at the Point-of-Care

Abstract

Chloroquine is an important, and commonly prescribed, antimalarial drug which can lead to the development of retinopathy and potential blindness. This paper reports on the design and fabrication of a highly selective potentiometric sensor for chloroquine, demonstrating the first use of ionophore-doped ion-selective electrodes (ISEs) for its detection. Several molecules, with known affinity for chloroquine, were investigated as potential ionophores for the chloroquine ISE. Incorporating melanin as the ionophore resulted in a linear detection range of 10 mM to 2.4 μM and a limit of detection of 630 nM. Importantly, the melanin-doped ISE resulted in an increased selectivity by several orders of magnitude compared to an ionophore-free ISE. This added selectivity allowed for detection of chloroquine without interference from other commonly prescribed antimalarials, hydroxychloroquine and quinine that have similar molecular structures. To determine the applicability of the melanin-doped ISE, chloroquine was successfully measured in human urine samples, and the results of the sensor were validated using a High-Performance Liquid Chromatography (HPLC) protocol. To demonstrate the utility of the sensor, the components of the ISE were translated to a paper-based potentiometric device capable of detecting chloroquine between 10 mM and 100 μM, covering the biologically relevant range excreted in human urine.