Precise field-friendly methods for quantification of antimalarial drugs in dried blood spots

Project Summary/Abstract Quantification of drugs using the dried blood spots (DBS) remains uncommon due to the challenges of variability of DBS samples and correlation of DBS drug levels with plasma drug levels and clinical outcomes. In this proposal, we employ the volumetric absorptive microsampling (VAMS) technique to collect DBS samples and use ultra-performance liquid chromatography tandem mass spectrometry to build a platform for quantitation of antimalarial drugs, including lumefantrine, amodiaquine and its metabolite desethylamodiaquine, and piperaquine, in the DBS samples. Then we will establish the correlation of DBS-plasma drug concentrations. Considering the unequal distribution of drugs in erythrocytes and plasma, high protein binding, and variable hematocrit, comprehensive regression models will be tested to improve the accuracy of DBS-plasma conversion of drug concentrations. VAMS technique enables precise sampling of micro-volume samples regardless of hematocrit. such as Mitra™ DBS devices collecting 10 µL blood and HemaPEN™ DBS devices collecting 2.74 µL blood samples with precision and accuracy <5%. DBS microsampling can be carried out easily by patients, requires less blood volume, and can be stored and transported at room temperature. The novel VAMS DBS microsampling for sample collection combined with the highly sensitive ultra-performance liquid chromatography tandem mass spectrometry for drug quantitation, if successfully validated, can be used as general methods to support pharmacokinetic/ pharmacodynamic studies in rural area where blood samples processing and cold storage are impossible. We also expect an increasing application for pediatric patients due to its advantage over traditional plasma samples. Finally, we will explore association of DBS drug exposure and risk of malaria in comparison of the established association of plasma drug concentrations and risk of malaria.