Tian Jiye, Feng Chunpeng, Xue Hongyu, You Jiansong, Shi Meiyun, Yin Lei
Cancer Hospital of Dalian University of Technology, Dalian University of Technology, Shenyang, 110042, China.
School of Chemical Engineering, Ocean and Life Sciences, Dalian University of Technology, Panjin, Liaoning, 124221, China.
Anal Methods. 2025 Mar 27;17(13):2676-2685. doi: 10.1039/d4ay02050b.
Propionic acid-polyethylene glycol-propionic acid (PA-PEG-PA) is a commonly used biocompatible polymer in drug delivery systems. Unraveling the pharmacokinetic behavior of PA-PEG-PA polymer is important for the safety evaluation of PA-PEG-PA related drug delivery systems. In this research, a highly sensitive ultra-high performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) assay was developed for detection of PA-PEG-PA polymers in complex biological matrices. Methoxy-polyethylene glycol propionic acid polymers with 6 subunits (mPEG-PA) were used as the internal standard (IS). The multiple reaction monitoring (MRM) transitions at / 513.4 ([M - H] precursor ions) → 441.2 (fragment ions) and / 367.3 ([M - H] precursor ions) → 118.8 (fragment ions) were chosen to determine PA-PEG-PA and mPEG-PA, respectively. The analysis time was only 5 min for each sample. Numerous parameters like specificity, sensitivity, accuracy, precision, recoveries, matrix effects and dilution effect were validated for the developed assay. The UPLC-MS/MS assay showed excellent linearity over the range of 30-1500 ng mL( > 0.995). The assay was successfully applied to quantify the concentration of PA-PEG-PA polymers in rat plasma.
丙酸 - 聚乙二醇 - 丙酸（PA - PEG - PA）是药物递送系统中常用的生物相容性聚合物。阐明PA - PEG - PA聚合物的药代动力学行为对于PA - PEG - PA相关药物递送系统的安全性评估至关重要。在本研究中，开发了一种高灵敏度的超高效液相色谱串联质谱（UPLC - MS/MS）分析法，用于检测复杂生物基质中的PA - PEG - PA聚合物。具有6个亚基的甲氧基聚乙二醇丙酸聚合物（mPEG - PA）用作内标（IS）。分别选择/ 513.4（[M - H]前体离子）→441.2（碎片离子）和/ 367.3（[M - H]前体离子）→118.8（碎片离子）的多反应监测（MRM）跃迁来测定PA - PEG - PA和mPEG - PA。每个样品的分析时间仅为5分钟。针对所开发的分析方法，对特异性、灵敏度、准确性、精密度、回收率、基质效应和稀释效应等众多参数进行了验证。UPLC - MS/MS分析方法在30 - 1500 ng/mL范围内显示出优异的线性（> 0.995）。该分析方法已成功应用于定量大鼠血浆中PA - PEG - PA聚合物的浓度。
