de Andrade Débora Coelho, Monteiro Sofia Aquino, de Oliveira Tiago Espinosa, Merib Josias
Programa de Pós-Graduação Em Biociências, Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, 90050-170, RS, Brazil.
Departamento de Farmacociências, Universidade Federal de Ciências da Saúde de Porto Alegre, 245, Sarmento Leite St., Porto Alegre, 90050-170, RS, Brazil.
Anal Bioanal Chem. 2025 Mar;417(7):1305-1315. doi: 10.1007/s00216-024-05560-x. Epub 2024 Sep 27.
Natural deep eutectic solvents (NADES) are gaining significant attention in analytical chemistry due to attractive physico-chemical properties associated with sustainable aspects. They have been successfully evaluated in different fields, and applications in sample preparation have increased in the last years. However, there is a limited knowledge related to chemical interactions and mechanism of intermolecular action with specific analytes. In this regard, for the first time, this study exploited a computational investigation using molecular dynamics (MD) predictions combined with experimental data for the extraction/determination of steroidal hormones (estriol, β-estradiol, and estrone) in urine samples using NADES. The ultrasound-assisted liquid-liquid microextraction (UALLME) approach followed by high-performance liquid chromatography with diode array detection (HPLC-DAD) was employed using menthol:decanoic acid as extraction solvent. Experimental parameters were optimized through multivariate strategies, with the best conditions consisting of 3 min of extraction, 150 μL of NADES, and 3 mL of sample (tenfold diluted). According to molecular dynamics predictions confirmed by experimental data, a molar ratio that permitted the highest efficiency consisted of menthol:decanoic acid 2:1 v/v. Importantly, computational simulations revealed that van der Waals interactions were the most significant contributor to the interaction energy of analytes-NADES. Using the optimized conditions, limits of detection (LOD) ranged from 3 and 8 μg L, and precision (n = 3) varied from 8 to 19%. Intraday precision was evaluated at 3 concentrations: low (LOQ according to each analyte), medium (100 μg L), and high (750 μg L). Accuracy was successfully assessed through recoveries that ranged from 82 to 98%. In this case, molecular dynamics simulations proved to be an important tool for in-depth investigations of interaction mechanisms of DES with different analytes.
天然深共熔溶剂（NADES）因其具有与可持续性相关的吸引人的物理化学性质而在分析化学中受到广泛关注。它们已在不同领域得到成功评估，并且在过去几年中，其在样品制备中的应用有所增加。然而，关于与特定分析物的化学相互作用和分子间作用机制的知识有限。在这方面，本研究首次利用分子动力学（MD）预测结合实验数据进行计算研究，以使用NADES萃取/测定尿液样品中的甾体激素（雌三醇、β-雌二醇和雌酮）。采用薄荷醇：癸酸作为萃取溶剂，采用超声辅助液-液微萃取（UALLME）方法，随后进行配有二极管阵列检测的高效液相色谱法（HPLC-DAD）。通过多变量策略优化实验参数，最佳条件为萃取3分钟、150μL NADES和3mL样品（十倍稀释）。根据实验数据证实的分子动力学预测，效率最高的摩尔比为薄荷醇：癸酸2:1 v/v。重要的是，计算模拟表明范德华相互作用是分析物与NADES相互作用能的最主要贡献因素。使用优化条件时，检测限（LOD）范围为3至8μg/L，精密度（n = 3）在8%至19%之间变化。在3个浓度下评估日内精密度：低浓度（根据每种分析物的定量限）、中浓度（100μg/L）和高浓度（750μg/L）。通过82%至98%的回收率成功评估了准确度。在这种情况下，分子动力学模拟被证明是深入研究DES与不同分析物相互作用机制的重要工具。
