School of Life Science and Medicine, Dalian University of Technology, NO.2 Dagong Road, New District of Liaodong Bay, Panjin 124221, PR China.
School of Life Science and Medicine, Dalian University of Technology, NO.2 Dagong Road, New District of Liaodong Bay, Panjin 124221, PR China.
J Chromatogr B Analyt Technol Biomed Life Sci. 2019 Sep 1;1125:121716. doi: 10.1016/j.jchromb.2019.121716. Epub 2019 Jul 10.
Poly(ethylene glycol)-block-poly(lactic acid) (PEG-PLA) is a biocompatible and amphiphilic block copolymer composed of a hydrophilic PEG block and a hydrophobic PLA block, which can self-assemble into micelles in water. It is one of the most commonly used biodegradable polymers for drug encapsulation, drug solubilization and drug delivery. Due to the complexity and heterogeneity of PEG-PLA, the precise analysis of this polymer is a great challenge. This study reports an application of an UPLC tandem mass spectrometry coupled with in-source collision induced dissociation (CID) technique for the analysis of a model compound mPEG2000-PDLLA2500-COOH, which could be dissociated in source and generate a series of fragment ions corresponding to its subunits. These surrogate ions including PLA-specific and PEG-specific fragment ions could be further broken into specific product ions in collision cell. Finally, the ion transition at m/z 505.0 → 217.0 was selected for the quantitation of mPEG2000-PDLLA2500-COOH. This assay achieved a lower limit of quantitation (LLOQ) of 0.05 μg/mL with only 30 μL rat plasma. The linear range is 0.05 to 5 μg/mL. Intraday and interday accuracy and precision were within ±12.1%. The method was successfully applied to the pharmacokinetic study of mPEG2000-PDLLA2500-COOH in rats. The results revealed that LC-MS/MS coupled with in-source CID is a sensitive and specific strategy for analysis of PEG-PLA. This method can be potentially extended to the analysis of other pharmaceutical polymer excipients.
聚乙二醇-聚乳酸（PEG-PLA）是一种生物相容的两亲性嵌段共聚物，由亲水性的聚乙二醇（PEG）嵌段和疏水性的聚乳酸（PLA）嵌段组成，在水中可以自组装成胶束。它是最常用于药物包封、药物增溶和药物递送的可生物降解聚合物之一。由于 PEG-PLA 的复杂性和异质性，对这种聚合物的精确分析是一个巨大的挑战。本研究报告了一种超高效液相色谱串联质谱法（UPLC-MS/MS）与源内碰撞诱导解离（CID）技术在分析模型化合物 mPEG2000-PDLLA2500-COOH 中的应用，该模型化合物可以在源内解离，并产生一系列与其亚基相对应的碎片离子。这些替代离子包括 PLA 特异性和 PEG 特异性的碎片离子，可以在碰撞池中进一步碎裂成特定的产物离子。最后，选择 m/z 505.0→217.0 的离子跃迁用于定量 mPEG2000-PDLLA2500-COOH。该测定法在 30 μL 大鼠血浆中实现了 0.05 μg/mL 的定量下限（LLOQ）。线性范围为 0.05 至 5 μg/mL。日内和日间准确度和精密度均在±12.1%范围内。该方法成功应用于 mPEG2000-PDLLA2500-COOH 在大鼠体内的药代动力学研究。结果表明，LC-MS/MS 与源内 CID 相结合是一种分析 PEG-PLA 的灵敏和特异的策略。该方法可以潜在地扩展到其他药物聚合物赋形剂的分析。
