Determination of benznidazole in human dried blood spots by liquid chromatography-mass spectrometry to monitor adherence to trypanosoma cruzi infection treatment in infants and children

Medication adherence is critical to the effectiveness of benznidazole (BZ) therapy for the treatment of Chagas disease. Assessing BZ adherence using traditional plasma sampling methods presents numerous challenges in resource-limited settings. Dried blood spot (DBS) sampling ofBZcan be used to overcome logistical barriers and provides a less invasive method for assessing BZ levels. ABZDBSassay using liquid chromatography-tandem mass spectrometry was developed and applied to a clinical study of infants and children being treated withBZ for Trypanosoma cruzi infection in Argentina. The assay was validated over a concentration range of 9.8-5,000 ng/mL. Inter-assay and intra-assay measures ranged from -2.9% to 2.7% and 0.5% to 8.3% for accuracy and from 3.5% to 12% and 1.6% to 13.6% for precision, respectively. The mean recovery of BZ was greater than 91%. Partitioning ratios for DBSs/plasma ranged from 0.95 to 1.02. A cohort of 10 infants and six children with T. cruzi infection being treated with BZ had median BZ concentrations of 1.2 (IQR 0.29, 2.14) μg/mL with seven of 65 (11%) samples above the BZ treatment goal of 3 μg/mL for adults. The reported DBS assay is a simple and accurate method for the quantitative measurement of BZ that can be applied to facilitate urgently needed clinical studies of BZfor the treatment of Chagas disease and assessBZadherence in resource-limited settings.Fil: Momper, Jeremiah D.. University of California at San Diego; Estados UnidosFil: Hanan, Nathan J.. University of California at San Diego; Estados UnidosFil: Rossi, Steven S.. University of California at San Diego; Estados UnidosFil: Mirochnick, Mark H.. Boston University; Estados UnidosFil: Cafferata, Maria Luisa. No especifíca;Fil: Lavenia, Antonia. Ministerio de Salud Pública de la Provincia de Tucumán; ArgentinaFil: Flores, Isolina. Ministerio de Salud Pública de la Provincia de Tucumán; ArgentinaFil: Gibbons, Luz. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Ciganda, Alvaro. No especifíca;Fil: Sosa-Estani, Sergio Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; Argentina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán"; ArgentinaFil: Capparelli, Edmund V.. University of California at San Diego; Estados UnidosFil: Buekens, Pierre. University of Tulane; Estados Unido