Unraveling the cytotoxicity and cellular pharmacokinetic of mPEG5-NH2 polymers by UHPLC-MS/MS

IF 3.1 3区医学 Q2 CHEMISTRY, ANALYTICAL

Journal of pharmaceutical and biomedical analysis Pub Date : 2025-02-25 DOI:10.1016/j.jpba.2025.116767

Yingxia Guo , Meichen Liu , Yajie Cheng , Jiye Tian , Chunpeng Feng , Qingbin Wang , Xuan Zhao , Lei Yin

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引用次数: 0

Abstract

Methoxy-polyethylene glycol amine (mPEG-NH₂), an important pharmaceutical excipient, has been extensively utilized in the field of biomedicine. To advance the development of mPEG-NH₂-related drug delivery systems, it is crucial to understand the safety profile and cellular pharmacokinetic behavior of mPEG-NH₂ polymers. In this study, a straightforward analytical assay based on ultra-high performance liquid chromatography and tandem mass spectrometry (UHPLC-MS/MS) for quantifying mPEG₅-NH₂ in biological matrices was established and validated. Multiple reaction monitoring (MRM) transitions were selected for quantification of mPEG₅-NH₂ (mass-to-charge ratio, m/z 252.1 → 87.7) and octaethylene glycol (OH-PEG₈-OH) (mass-to-charge ratio, m/z 371.2 → 89.2). The UHPLC-MS/MS assay demonstrated excellent linearity within the concentration range of 0.01–10 μg/mL, with an R² value of 0.9996. Both intra-day and inter-day accuracies and precisions of the analytical method were within ± 9.19 %. This analytical assay was successfully applied to study the in vitro cellular toxicity and uptake behavior of mPEG₅-NH₂ in MCF-7 cells. The results indicate that high doses of mPEG₅-NH₂ may have potential toxicity to MCF-7 cells.

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来源期刊

Journal of pharmaceutical and biomedical analysis 医学-分析化学

CiteScore

6.70

自引率

5.90%

发文量

588

审稿时长

37 days

期刊介绍： This journal is an international medium directed towards the needs of academic, clinical, government and industrial analysis by publishing original research reports and critical reviews on pharmaceutical and biomedical analysis. It covers the interdisciplinary aspects of analysis in the pharmaceutical, biomedical and clinical sciences, including developments in analytical methodology, instrumentation, computation and interpretation. Submissions on novel applications focusing on drug purity and stability studies, pharmacokinetics, therapeutic monitoring, metabolic profiling; drug-related aspects of analytical biochemistry and forensic toxicology; quality assurance in the pharmaceutical industry are also welcome. Studies from areas of well established and poorly selective methods, such as UV-VIS spectrophotometry (including derivative and multi-wavelength measurements), basic electroanalytical (potentiometric, polarographic and voltammetric) methods, fluorimetry, flow-injection analysis, etc. are accepted for publication in exceptional cases only, if a unique and substantial advantage over presently known systems is demonstrated. The same applies to the assay of simple drug formulations by any kind of methods and the determination of drugs in biological samples based merely on spiked samples. Drug purity/stability studies should contain information on the structure elucidation of the impurities/degradants.