Validated ICP-MS method for measurement of plasma and intracellular antimony concentrations applied to pharmacokinetics of meglumine antimoniate

Abstract

Aim A high-throughput method using inductively coupled plasma mass spectrometry (ICP-MS) was developed and validated for the quantitative analysis of antimony in human plasma and peripheral blood mononuclear cells (PBMCs) from patients with cutaneous leishmaniasis undergoing treatment with meglumine antimoniate. Methods For this study, antimony was digested in clinical samples with 1% TMAH / 1% EDTA and indium was used as internal standard. Calibration curves for antimony, over the range of 25 to 10000 ng/mL were fitted to a linear model using a weighting of 1/concentration2. Accuracy, precision and stability were evaluated. Results Taking the lower limit of quantitation (LLOQ) to be the lowest validation concentration with precision and accuracy within 20% (25% at the LLOQ), the current assay was successfully validated from 25 to 10000 ng/mL for antimony in human plasma and PBMCs. Dilution studies demonstrated that concentrations up to 100000 ng/mL of antimony in plasma were reliably analyzed when diluted into the calibration range. Conclusion This protocol will serve as a baseline for future analytical designs, aiming to provide a reference method to allow inter-study comparisons.