Direct Determination of Lithium in Dried Blood Spots: A Minimally Invasive and Accurate Analytical Alternative

Abstract The present study evaluates the applicability of dried blood spot (DBS) sampling for the direct determination of lithium (Li) in whole blood and human serum using solid sampling high-resolution continuum source graphite furnace atomic absorption spectrometry (SS HR-CS GFAAS). DBS represents a minimally invasive and practical sampling approach, with advantages in storage, transport, and handling. Sample volumes in 3 mm DBS discs were estimated at 3.0 µL, and a modified “precut saturated” technique was applied to ensure uniform analyte distribution. The SS HR-CS GFAAS method was optimized, including the selection of the 670.7845 nm Li atomic line, the use of iridium as a permanent chemical modifier, and refinement of pyrolysis (950 °C) and atomization (2500 °C) parameters, ramps, and hold time. Calibration was successfully performed using both aqueous standards and standards over a Whatman ™ card disc, with negligible matrix effects under optimized conditions. The method demonstrated excellent analytical performance. The limits of detection and quantification were 0.25 and 5.74 pg, respectively, the intra- and inter-day relative standard deviations were 1.3%–6.2% and 3.5%–7.4%, respectively, and the recoveries ranged from 94.3% to 107.4%. Accuracy was confirmed using certified reference materials, and statistical analysis revealed no significant differences between experimental and certified values. These results demonstrate that DBS sampling coupled with SS HR-CS GFAAS provides a sensitive, precise, and robust approach for lithium monitoring in clinical and research settings. The simplicity of sample collection, transport, and storage, together with the rapidity and relatively low cost of the analytical method employed, makes the proposed procedure highly suitable for the monitoring of individuals undergoing lithium therapy. Such an approach provides a practical tool for identifying patients whose blood lithium concentrations exceed clinically acceptable limits, thereby supporting safer and more effective therapeutic management.