Synthesis of Perfluorooctyl-Functionalized Halloysite Nanotubes for Dispersive Solid-Phase Extraction of Antimalarial Inhibitors in Whole Blood

Abstract

Quinine, chloroquine, and hydroxychloroquine are effective antimalarial drugs that have shown antiviral activity against SARS-CoV-2 in initial in vitro studies. However, their excessive use can lead to adverse effects in humans. Therefore, rapid and accurate analysis of these inhibitors in whole blood samples is crucial for public health, although this presents significant challenges. In this study, perfluorooctyl-functionalized halloysite nanotubes were synthesized and used as sorbents for dispersive solid-phase extraction. The developed sorbents interacted with inhibitors through various mechanisms, including hydrophobic interactions, electrostatic interactions, F–π interactions, and hydrogen bonding. Notably, their adsorption capacity was twice that of unmodified halloysite nanotubes. By combining the perfluorooctyl-functionalized halloysite nanotubes-based dispersive solid-phase extraction method with liquid chromatography-tandem mass spectrometry, an analytical method was developed to determine concentrations of the three inhibitors in whole blood samples. Under optimized conditions, the limits of detection ranged from 1.2 to 2.1 ng/mL. The recoveries achieved 91.9%–101.5% for intra-day and 92.8%–101.2% for inter-day. The inter- and intra-day relative standard deviations were in the range of 0.6%–3.8% and 2.3%–8.1%, respectively. This study introduces a novel approach for developing sorbents to target drugs and presents an innovative analytical method for therapeutic monitoring. These advancements will facilitate the evaluation of the pharmacokinetics of these inhibitors in patients and support ongoing clinical trials.