Aminophylline (AMP) is a bronchodilator. The therapeutic and toxic doses are very close. Therefore, therapeutic drug monitoring (TDM) of AMP is essential in clinical practice. Microgels were synthesized by free radical precipitation polymerization. Silver@poly( N-isopropyl acrylamide) (Ag@PNIPAM) hybrid microgels were obtained by loading silver (Ag) nanoparticles into the three-dimensional network of the microgels by in situ reduction. The microgel is a three-dimensional reticular structure with tunable pore size, large specific surface area, and good biocompatibility, which can be used as a sorbent for solid-phase extraction (SPE) of target molecules in complex matrices and as a surface-enhanced Raman spectroscopy (SERS) substrate. We optimized the conditions affecting SERS enhancement, such as silver nitrate (AgNO3) concentration and SPE time, according to the SERS strategy of Ag@PNIPAM hybrid microgels to achieve label-free TDM for trace AMP in human serum. The results showed good linearity between the logarithmic concentration of AMP and its SERS intensity in the range of 1–1.1 × 102 µg/mL, with a correlation coefficient ( R2) of 0.9947 and a low detection limit of 0.61 µg/mL. The assay accuracy was demonstrated by spiking experiments, with recoveries ranging from 93.0 to 101.8%. The method is rapid, sensitive, reproducible, requires simple sample pretreatment, and has good potential for use in clinical treatment drug monitoring.

中文翻译：

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使用水凝胶微球耦合表面增强拉曼光谱 (SERS) 和固相萃取测定人血清中的氨茶碱

氨茶碱 (AMP) 是一种支气管扩张剂。治疗剂量和毒性剂量非常接近。因此，AMP 的治疗药物监测（TDM）在临床实践中至关重要。通过自由基沉淀聚合合成微凝胶。通过原位还原将银（Ag）纳米粒子负载到微凝胶的三维网络中，得到银@聚（N-异丙基丙烯酰胺）（Ag@PNIPAM）杂化微凝胶。该微凝胶具有三维网状结构，孔径可调、比表面积大、生物相容性好，可作为复杂基质中目标分子固相萃取（SPE）的吸附剂和表面增强剂。拉曼光谱 (SERS) 基板。我们优化了影响SERS增强的条件，例如硝酸银（AgNO3）浓度和SPE时间，根据Ag@PNIPAM混合微凝胶的SERS策略，实现人血清中痕量AMP的免标记TDM。结果表明，AMP的对数浓度与其SERS强度在1~1.1×10范围内具有良好的线性关系2µg/mL，相关系数 ( R2) 为 0.9947，检测下限为 0.61 µg/mL。通过加标实验证明了测定的准确性，回收率范围为 93.0 至 101.8%。该方法快速、灵敏、重现性好，样品前处理简单，在临床治疗药物监测中具有良好的应用潜力。