泊洛沙姆是FDA批准的应用广泛的药用高分子聚合物，但是存在与药理毒理密切相关的药代动力学及潜在毒性问题，其定量分析方法更是困扰药物分析和药代动力学领域多年的技术难题。传统的定量分析方法无法准确评价泊洛沙姆质量的优劣，无法避免相同质荷比的化学噪音干扰，无法精准评价体内药动学行为。本课题在前期工作基础上，基于液相色谱-高分辨质谱的连续可变窗口采集先进技术，为泊洛沙姆定量分析提供了可能的解决方案。本课题拟以不同聚合度的泊洛沙姆为研究对象，采用不同的质谱裂解和扫描模式，结合色谱技术，研究质谱裂解规律，建立选择性强、灵敏度高的定量分析方法，并将该方法应用于泊洛沙姆的细胞水平转运、肝微粒体代谢以及整体动物的药代动力学研究中。这些研究将解决泊洛沙姆定量分析的瓶颈问题，为其质量控制和药代动力学研究提供新的思路和方法，进一步阐明泊洛沙姆逆转肿瘤多药耐药的作用机制，促进基于泊洛沙姆载药体系的药物研究与开发。

Poloxamer is a kind of widely used polymer excipient approved by FDA. However, some pharmacokinetic challenges and potential toxic problems still exist relating to pharmacology and toxicology. The quantitative analysis of poloxamer is a major hurdler in the area of pharmaceutical analysis and pharmacokinetics for many years. The conventional quantitatively analytical methods could not accurately determine poloxamer and resolve the interferences from the compounds with the same mass-to-charge ratio as poloxamer which leads to inaccurate evaluation of its pharmacokinetic behavior. The SWATH technology based on LC-HR-MS/MS provides a feasible method to quantitate poloxamer according to our previous research. In this project, poloxamer with different degrees of polymerization was selected, and a selective and sensible quantitative method was developed to investigate the fragmentation rules of poloxamer combined with chromatographic separation, different mass fragmentation and scan modes. The established method will be applied to study cellular transport, metabolism with liver microsomes and pharmacokinetics of poloxamer. These studies will solve the bottleneck problem of the quantitative analysis of poloxamer, provide new ideas and methods for its quality control and pharmacokinetic research, and clarify the multidrug resistance mechanism of poloxamer for reversing tumor. Moreover, this project will be helpful to promote the research and development of drug delivery system based on poloxamer.