Abstract：
Therapeutic drug monitoring is essential for ensuring the efficacy and safety of medications. This study introduces a streamlined approach that combines pipette-tip solid-phase extraction (PT-SPE) with matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS), facilitating rapid and high-throughput monitoring of drug concentrations. As a demonstration, this method was applied to the extraction and quantification of antidepressants in serum. Utilizing Zip-Tip C18, the method enabled the extraction of antidepressants from complex biological matrices in less than 2 min, with the subsequent MALDI-MS analysis yielding results in just 1 min. Optimal extraction recoveries were achieved using a sampling solution at pH 9.0 and a 10 μL ethanol desorption solution containing 0.1% phosphoric acid. For MALDI analysis, 2,5-dihydroxybenzoic acid was identified as the most effective matrix for producing the highest signal intensity. The quantification strategy exhibited robust linearities (R2 ≥ 0.997) and satisfactory limits of quantification, ranging from 0.05 to 0.5 μg/mL for a suite of antidepressants. The application for monitoring dynamic concentration changes of antidepressants in rat serum emphasized the method\'s efficacy. This strategy offers the advantages of high throughput, minimal sample usage, environmental sustainability, and simplicity, providing ideas and a reference basis for the subsequent development of methods for therapeutic drug monitoring.
摘要：
治疗药物监测对于确保药物的有效性和安全性至关重要。本研究引入了一种简化的方法，该方法将移液管尖端固相萃取（PT-SPE）与基质辅助激光解吸/电离质谱（MALDI-MS）相结合，促进药物浓度的快速和高通量监测。作为一个示范,该方法用于血清中抗抑郁药的提取和定量。利用Zip-TipC18，该方法能够在不到2分钟的时间内从复杂的生物基质中提取抗抑郁药，随后的MALDI-MS分析仅在1分钟内产生结果。使用pH9.0的采样溶液和含有0.1％磷酸的10μL乙醇解吸溶液实现了最佳提取回收率。对于MALDI分析，2,5-二羟基苯甲酸被确定为产生最高信号强度的最有效基质。量化策略表现出稳健的线性度(R2≥0.997)和令人满意的量化限，范围从0.05到0.5μg/mL的一组抗抑郁药。应用动态监测大鼠血清中抗抑郁药浓度变化强调了该方法的有效性。这种策略提供了高吞吐量的优点，最小的样本使用量，环境可持续性,和简单，为后续治疗药物监测方法的发展提供思路和参考依据。
