Abstract：
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.
摘要：
氨茶碱(AMP)是支气管扩张剂。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了微凝胶。通过原位还原将银（Ag）纳米颗粒加载到微凝胶的三维网络中，获得了银@聚（N-异丙基丙烯酰胺）（Ag@PNIPAM）杂化微凝胶。微凝胶是具有可调孔径的三维网状结构，大的比表面积，良好的生物相容性,它可以用作复杂基质中靶分子的固相萃取（SPE）的吸附剂，也可以用作表面增强拉曼光谱（SERS）底物。我们优化了影响SERS增强的条件，如硝酸银（AgNO3）浓度和SPE时间，根据Ag@PNIPAM杂化微凝胶的SERS策略实现人血清中微量AMP的无标记TDM。结果表明，AMP的对数浓度与其SERS强度在1-1.1×102µg/mL范围内呈良好的线性关系，相关系数（R2）为0.9947，低检测限为0.61µg/mL。通过加标实验证明了测定的准确性，回收率从93.0到101.8%不等。该方法是快速的，敏感,可重复,需要简单的样品预处理，并具有很好的应用于临床治疗药物监测的潜力。
