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基于碰撞诱导解离技术的高效液相色谱串联质谱法定量分析聚丙二醇聚合物。

Quantitative analysis of polypropylene glycol polymers by liquid chromatography tandem mass spectrometry based on collision induced dissociation technique.

机构信息

School of Life and Pharmaceutical Sciences, Dalian University of Technology, Panjin, 124221, PR China; Aim Honesty Biopharmaceutical Co. LTD, Dalian, 116600, PR China.

School of Life and Pharmaceutical Sciences, Dalian University of Technology, Panjin, 124221, PR China.

出版信息

J Chromatogr A. 2022 Aug 2;1676:463214. doi: 10.1016/j.chroma.2022.463214. Epub 2022 Jun 11.

Abstract

Polypropylene glycol (PPG) is a commonly used synthetic polymer in many fields. Investigating the toxicity and pharmacokinetic behavior of PPG polymers is necessary and important for evaluating their safety in medicine and daily cosmetics. In this study, PPG425, PPG1K and PPG2K were selected as the target polymers for cytotoxicity and cellular pharmacokinetics study of PPG polymers. Structural diversity and polydisperse molecular weights (MWs) are significant challenges for quantification of PPG polymers by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Collision induced dissociation in source or collision cell generated a series of PPG-related product ions at m/z 59.0, 117.1, 175.1, 233.2, 291.2, 349.3, 407.2, 465.3 and 523.5 corresponding to fragments containing 1, 2, 3, 4, 5, 6, 7, 8, 9 repeating propylene oxide subunits. PPG425 was determined by the sum of the MRM acquisitions used the transitions [M+H] precursor ions → product ions. PPG1K and PPG2K were determined by the MRM acquisitions used the transitions [M+H] precursor ions → product ions at m/z 233.2(four subunits)→59.0(one subunit). Based on the collision induced disassociation technique and structural specific product ions, pharmacokinetic studies of PEG425, PPG1K and PPG2K were successfully conducted in McF-7 cells. The experimental results revealed that PPG polymers are not biologically inert and they can enter into McF-7 cells. The safety of PPG polymers should be considered when they are used as pharmaceutical or cosmetic excipients.

摘要

聚丙二醇(PPG)是许多领域常用的合成聚合物。研究 PPG 聚合物的毒性和药代动力学行为对于评估其在医药和日常化妆品中的安全性是必要且重要的。在本研究中,选择 PPG425、PPG1K 和 PPG2K 作为 PPG 聚合物细胞毒性和细胞药代动力学研究的目标聚合物。结构多样性和多分散分子量(MW)是通过液相色谱-串联质谱(LC-MS/MS)定量 PPG 聚合物的重大挑战。在源或碰撞池中进行碰撞诱导解离会在 m/z 59.0、117.1、175.1、233.2、291.2、349.3、407.2、465.3 和 523.5 处产生一系列与 PPG 相关的产物离子,这些产物离子对应于含有 1、2、3、4、5、6、7、8、9 个重复环氧丙烷单元的片段。PPG425 通过使用 [M+H]+前体离子→产物离子的 MRM 采集总和来确定。PPG1K 和 PPG2K 通过使用 [M+H]+前体离子→产物离子在 m/z 233.2(四个亚基)→59.0(一个亚基)的 MRM 采集来确定。基于碰撞诱导解离技术和结构特异性产物离子,成功地在 McF-7 细胞中进行了 PPG425、PPG1K 和 PPG2K 的药代动力学研究。实验结果表明,PPG 聚合物不是生物惰性的,它们可以进入 McF-7 细胞。在将 PPG 聚合物用作药物或化妆品赋形剂时,应考虑其安全性。

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