Abstract：
Determination of antiepileptic drugs and antipsychotics in human serum is significant in individualized drug administration and therapeutic drug monitoring (TDM). In this study, we developed a rapid label-free TDM method for the antiepileptic drug carbamazepine (CBZ) and the antipsychotic clozapine (CLO) in human serum. This detection strategy is based on the combination of surface-enhanced Raman scattering (SERS) and magnetic solid-phase extraction (MSPE). Initially, Fe3O4@SiO2@MIL-101(Fe) nanocomposites were synthesized by the layer-by-layer self-assembly method and characterized using scanning electron microscopy, transmission electron microscopy, X-ray diffraction, Brunauer-Emmett-Teller, ultraviolet-visible, and Fourier transform infrared analyses. Subsequently, CBZ and CLO were detected in human serum using Fe3O4@SiO2@MIL-101(Fe) as the solid-phase extraction adsorbent and Ag nanoparticles as SERS substrates. The potential of the MSPE-SERS method for the label-free TDM of CBZ and CLO was then investigated. Fe3O4@SiO2@MIL-101(Fe) prevents magnetic particle aggregation and demonstrates rapid magnetic separation capability that simplifies the pretreatment process and reduces interference from complex matrices. Its large surface area can effectively enrich targets in complex matrices, thereby improving the SERS detection sensitivity. The linearity between CBZ and CLO was excellent over the concentration range of 0.1-100 µg/mL (calculated as the intensity of the SERS characteristic peaks of CBZ and CLO at 728 cm and 1054 cm-1, respectively), with correlation coefficients (R2) of 0.9987 and 0.9957, and detection limits of 0.072 and 0.12 µg/mL, respectively. The recoveries of CBZ with CLO ranged from 94.0 % to 105.0 %, and their relative standard deviations were <6.8 %. Compared to other assays, the developed MSPE-SERS method has the advantages of simple sample pretreatment, rapid detection, and good reproducibility, which provides a novel approach for the TDM of other drugs.
摘要：
人血清中抗癫痫药物和抗精神病药物的测定对于个体化给药和治疗药物监测（TDM）具有重要意义。在这项研究中,我们开发了抗癫痫药卡马西平(CBZ)和抗精神病药氯氮平(CLO)在人血清中的快速无标记TDM方法.该检测策略基于表面增强拉曼散射（SERS）和磁性固相萃取（MSPE）的组合。最初，通过逐层自组装法合成了Fe3O4@SiO2@MIL-101（Fe）纳米复合材料，并使用扫描电子显微镜进行了表征，透射电子显微镜,X射线衍射,Brunauer-Emmett-Teller,紫外线可见光,和傅里叶变换红外分析。随后，以Fe3O4@SiO2@MIL-101(Fe)为固相萃取吸附剂,Ag纳米粒子为SERS底物,在人血清中检测CBZ和CLO。然后研究了MSPE-SERS方法对CBZ和CLO的无标记TDM的潜力。Fe3O4@SiO2@MIL-101（Fe）可防止磁性颗粒聚集，并具有快速的磁性分离能力，从而简化了预处理过程并减少了复杂基质的干扰。它的大表面积可以有效地丰富复杂矩阵中的目标，从而提高SERS检测灵敏度。在0.1-100µg/mL的浓度范围内，CBZ和CLO之间的线性良好（分别以CBZ和CLO在728cm和1054cm-1处的SERS特征峰的强度计算），相关系数（R2）为0.9987和0.9957，检出限为0.072和0.12µg/mL，分别。CBZ与CLO的回收率范围为94.0%至105.0%，相对标准偏差<6.8%。与其他化验相比，所开发的MSPE-SERS方法具有样品前处理简单的优点,快速检测,和良好的重现性，为其他药物的TDM提供了新的途径。
