Graduate Program on Toxicology and Analytical Toxicology, Feevale University, Novo Hamburgo, RS, Brazil; Laboratory of Analytical Toxicology, Institute of Health Sciences, Feevale University, Novo Hamburgo, RS, Brazil.
Laboratory of Analytical Toxicology, Institute of Health Sciences, Feevale University, Novo Hamburgo, RS, Brazil.
Talanta. 2020 Aug 15;216:120907. doi: 10.1016/j.talanta.2020.120907. Epub 2020 Mar 19.
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 (HNO 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 (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 and 0.17 to 0.92 mEq L in DBS and 0.15 to 0.99 mEq L 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+.
治疗药物监测（TDM）已成为心境稳定剂锂（Li）的标准治疗方法。干血斑（DBS）和干血浆斑（DPS）是 TDM 的有前途的替代采样策略，在许多环境中允许简单且具有成本效益的物流，特别是在发展中国家。DBS 和 DPS 特别适用于 Li + TDM，因为它们可以估计 Li +红细胞水平。因此，本研究的目的是开发和验证一种通过石墨炉原子吸收光谱法（GFAAS）测定 DBS 和 DPS 中 Li +的测定方法，并评估其在临床环境中的应用。用 4.5%硝酸从一个 8mm 的 DBS 圆盘冲头中提取 Li +，用稀释剂溶液（HNO 1%+Triton 0.1%）从一个 6mm 的 DPS 圆盘冲头中提取 Li +，并注入 GFAAS。该方法应用于 43 例心境障碍患者的 Li + TDM。在 0.10 至 3.0 mEq L 范围内，测定呈线性（r > 0.99），精确，DBS 和 DPS 样本的 CV 分别为 3.6-7.2%和 4.6-9.3%，准确，DBS 和 DPS 样本的准确度值分别为 97-109%和 98-106%。在 42°C 以下的干燥样品中，Li+在 20 天内稳定。DBS 测定的准确性和回收率不受血液红细胞压积的影响。患者的 Li +血清浓度分别为 0.18-1.1 mEq L 和 0.17-0.92 mEq L，DBS 和 0.15-0.99 mEq L 在 DPS 样本中。DPS 中的 Li +浓度与新鲜血清样本中的 Li +浓度相当。使用 DBS 样本，可以估计 Li +红细胞与血浆浓度比（LiR）。本研究的结果支持 DBS 和 DPS 样本在 Li + TDM 中的临床应用。
