Institute of Chemistry, Saratov State University, Astrakhanskaya 83, Saratov, 410012, Russia.
Institute of Chemistry, Saratov State University, Astrakhanskaya 83, Saratov, 410012, Russia.
Anal Chim Acta. 2020 May 1;1109:61-68. doi: 10.1016/j.aca.2020.02.067. Epub 2020 Mar 4.
The determination of antibiotic levels in body fluids is of great importance in the field of personalized medicine and therapeutic drug monitoring. We report on the determination of sulfamethoxazole (SMX), an antibacterial drug of the sulfanilamide class, in spiked human urine. The protocol is based on the combination of surface-enhanced Raman spectroscopy (SERS) and liquid-liquid extraction (LLE-SERS analysis). First, the urine was diluted to reduce its buffer properties and the influence of the intrinsic urine components on the background SERS signal. Second, the acidification of the diluted urine and SMX extracts was performed to facilitate SMX extraction by chloroform and suppress the background signal, respectively. Finally, the SMX determination process was performed using hydroxylamine-stabilized silver nanoparticles as the SERS substrate. The efficiency and reliability of the LLE-SERS analysis were studied using spiked urine samples obtained from healthy volunteers with an SMX content within the therapeutically relevant concentration range (10-200 μg mL). Additionally, the verification of the analysis protocol was done using spiked urine samples obtained from oncology patients. The results of the verification demonstrate the applicability of the analysis for quantitative therapeutic drug monitoring due to the (i) strong suppression of the background SERS signal, which occurs as the result of LLE, dilution, and pH adjusting, (ii) satisfactory limit of detection of 1.7 μg mL, and (iii) simple, relatively fast (∼30 min), and cost-effective sample pretreatment.
体液中抗生素水平的测定在个性化医学和治疗药物监测领域具有重要意义。我们报告了在加标人尿中测定磺胺类抗菌药物磺胺甲恶唑（SMX）的方法。该方案基于表面增强拉曼光谱（SERS）和液液萃取（LLE-SERS 分析）的结合。首先，稀释尿液以降低其缓冲性质，并减少尿液内源性成分对背景 SERS 信号的影响。其次，酸化稀释尿液和 SMX 提取物，分别促进氯仿萃取 SMX 和抑制背景信号。最后，使用羟胺稳定的银纳米粒子作为 SERS 基底进行 SMX 测定。使用来自健康志愿者的加标尿液样品（SMX 含量在治疗相关浓度范围内（10-200μgmL））研究了 LLE-SERS 分析的效率和可靠性。此外，还使用来自肿瘤患者的加标尿液样品对分析方案进行了验证。验证结果表明，由于（i）LLE、稀释和 pH 调节导致背景 SERS 信号得到强烈抑制，（ii）令人满意的检出限为 1.7μgmL，以及（iii）简单、相对快速（约 30 分钟）和具有成本效益的样品预处理，该分析方法可用于定量治疗药物监测。
