A simple alternative sampling method for benznidazole pharmacokinetic assessment: a dried blood spot technique-based LC-MS/MS method [Analytical Procedures]

Chagas Disease (CD) is recognized as one of the major global neglected tropical diseases. Benznidazole (BNZ) is the drug of choice for the treatment of adults, young infants, and newborns with CD. However, the pharmacokinetics (PK) of BNZ has been poorly evaluated in all age groups, with consequent gaps in knowledge about PK-PD relationships in CD. The purpose this study was to develop and validate a bioanalytical method to quantify BNZ levels in small volume whole blood samples collected as dried blood spots (DBS). The analysis was performed using high performance liquid chromatography positive electrospray tandem mass spectrometry. PK evaluation in healthy male volunteers was conducted to verify the correlation between DBS and plasma BNZ concentrations. The calibration curve was linear from 50 to 20,000 ng.mL^–1. Intra- and inter-day precisions and biases were less than 14.87% (n = 9) and 9.81% (n = 27), respectively. The recovery rates ranged from 94 to 100% and no matrix effect. There was no haematocrit level effect in a range of 20 to 70%. The PK results obtained from DBS and plasma were comparable (r² = 0.8295) and equivalent to previously published information on BNZ. BNZ in DBS was stable at room temperature for over one year. This article describes the first micro-sampling method for measuring BNZ levels in DBS that has the potential to facilitate broad implementation of PK in clinical trials involving adult and paediatric patients in remote endemic areas and help to address existing knowledge gaps in the treatment in CD.

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