Pharmaceutical Analysis Research Center, Tabriz University of Medicinal Science, Tabriz, Iran.
Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
J Pharm Biomed Anal. 2021 Jan 30;193:113659. doi: 10.1016/j.jpba.2020.113659. Epub 2020 Oct 4.
Acetic acid-functionalized magnetic nanoparticles modified by (3-amino-propyl)-tri-ethoxy silane was synthesized and used as a new solid-phases adsorbent. Infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), x-ray diffraction (XRD), energy-dispersive x-ray spectroscopy (EDX), vibrating sample magnetometer (VSM) and Electrophoretic Light Scattering (ELS) were used to characterize the modified nanoparticles. The molecular interaction between letrozole and nanoparticles (NPs) was studied using density functional theory (DFT) calculations. The developed nanoparticles were applied for dispersive solid-phase extraction of letrozole (an anticancer drug) from human plasma. Extracted letrozole was quantified using an isocratic HPLC/FL method. The extraction efficiency was optimized using one experiment at a time optimization method based on the adsorbent quantity, sample pH, adsorption time, desorption time, and elution solvent type/volume. The analysis method was fully validated according to the FDA guideline for bioanalytical method validation. The linear quantification range was 0.01-1 μg/mL and the lower limit of quantification (LLOQ) was 0.01 μg/mL. Plasma samples of 6 patients were analyzed and the measured letrozole concentrations range was 0.04-0.31 μg/mL. The newly synthesized magnetic nanoparticles were used successfully for the extraction of letrozole from spiked and clinical plasma samples. The developed method is a precise and simple method that is suitable for pharmacokinetic studies and clinical applications.
（3-氨丙基）三乙氧基硅烷修饰的乙酸功能化磁性纳米粒子被合成并用作新型固相吸附剂。采用傅里叶变换红外光谱（FT-IR）、扫描电子显微镜（SEM）、X 射线衍射（XRD）、能谱（EDX）、振动样品磁强计（VSM）和电泳光散射（ELS）对修饰后的纳米粒子进行了表征。采用密度泛函理论（DFT）计算研究了来曲唑与纳米粒子（NPs）之间的分子相互作用。开发的纳米粒子用于从人血浆中分散固相萃取来曲唑（一种抗癌药物）。采用等度 HPLC/FL 法定量萃取的来曲唑。采用基于吸附剂用量、样品 pH 值、吸附时间、解吸时间和洗脱溶剂类型/体积的一次实验优化方法优化了萃取效率。根据 FDA 生物分析方法验证指南对分析方法进行了全面验证。线性定量范围为 0.01-1μg/mL，定量下限（LLOQ）为 0.01μg/mL。分析了 6 名患者的血浆样品，测量的来曲唑浓度范围为 0.04-0.31μg/mL。新合成的磁性纳米粒子成功地用于从加标和临床血浆样品中提取来曲唑。所开发的方法是一种适合药代动力学研究和临床应用的精确而简单的方法。
