Determination of lithium in dried blood spots and dried plasma spots by graphite furnace atomic absorption spectrometry: Method development, validation and clinical application

Abstract

Therapeutic drug monitoring (TDM) has become a standard of care for the mood stabilizer lithium (Li+). Dried Blood Spots (DBS) and Dried Plasma Spots (DPS) are promising alternative sampling strategies for TDM, which allows simple and cost-effective logistics in many settings, particularly in Developing Countries. DBS and DPS are of particular interest to Li + TDM for allowing the estimation of Li + erythrocyte levels. Thus, the aim of this study was to develop and validate an assay for the determination of Li+ in DBS and DPS by Graphite Furnace Atomic Absorption Spectrometry (GFAAS), and to evaluate its application in a clinical setting. Li+ was extracted from one 8 mm DBS disc punch with nitric acid 4.5% and from one 6 mm DPS disc punch with diluent solution (HNO3 1% + Triton 0.1%) and injected into GFAAS. The method was applied to Li + TDM in 43 patients with mood disorder. The assays were linear from 0.10 to 3.0 mEq L−1 (r > 0.99), precise, with CV 3.6–7.2% for DBS and 4.6–9.3% for DPS samples, and accurate, with accuracy values of 97–109% and 98–106% for DBS and DPS samples, respectively. Li+ was stable in dried samples during twenty days at up to 42 °C. The DBS assay accuracy and recovery were not influenced by blood hematocrit. The patients presented Li + serum concentrations of 0.18–1.1 mEq L−1 and 0.17 to 0.92 mEq L−1 in DBS and 0.15 to 0.99 mEq L−1 in DPS samples. DPS had comparable Li + concentrations to the ones found in fresh serum samples. With DBS samples it was possible to estimate the Li + erythrocyte to plasma concentration ratio (LiR). The findings of this study support the clinical application of DBS and DPS samples for the TDM of Li+.