药用辅料星型乙交酯丙交酯共聚物中葡萄糖含量测定研究

目的： 建立LC-MS/MS分析方法测定星型乙交酯丙交酯共聚物（Glu-PLGA）中葡萄糖的含量，对比分析自制奥曲肽微球与善龙?奥曲肽微球（Sandostatin? LAR）在绝对分子量、支化度、葡萄糖含量等方面的差异。方法： 采用XBridge@Amide色谱柱（250 mm×4.6 mm，5 μm），以75%乙腈水溶液为流动相，等度洗脱，流速0.4 mL·min^-1；柱温35℃；进样量5 μL；采用负离子MRM扫描模式，质谱离子化方式为ESI，监测离子对m/z 179.0/89.1、179.0/71.1、179.0/59.2；应用凝胶渗透色谱三联检测系统测定Glu-PLGA绝对重均分子量和支化度。结果： 方法学试验考察结果表明，所建立的LC-MS/MS方法专属性，精密度，重复性良好，在0.001~0.02 mg·mL^-1浓度范围内线性关系良好（r=0.999 7，n=5），检测下限为0.000 2 mg·mL^-1、定量下限为0.000 67 mg·mL^-1，加标回收率（n=6）为93.6%，RSD为2.5%；对于善龙?奥曲肽微球与自制奥曲肽微球的研究，三联检测器和LC-MS/MS测定结果是微球1、微球2与善龙?奥曲肽微球基本一致。结论： 建立的测定Glu-PLGA中葡萄糖的含量LC-MS/MS分析方法相对方便简单，测定结果准确度和灵敏度高，三联检测器和LC-MS/MS方法可以对Glu-PLGA进行定性定量表征研究，为以后此类Glu-PLGA的研究提供借鉴。

Objective: To establish a LC-MS/MS method for determination of glucose content in star poly(lactide-co-glycolide) polymers(Glu-PLGA) and compare to Sandostatin? LAR and self-made microspheres from absolute molecular weight,degree of branching,and glucose content. Methods: Separation was performed on an XBridge@Amide column (250 mm×4.6 mm,5 μm) with 75% acetonitrile-water as the mobile phase at flow rate of 0.4 mL·min^-1. The column temperature was 35℃ and the sampling volumn was 5 μL. The samples were detected by using electrospray ion source ESI under negative ion MRM scanning mode. Choosing the characteristic molecular peaks of m/z 179.0/89.1,179.0/71.1,and 179.0/59. The absolute weight average molecular weight and branching degree of Glu-PLGA were determined by gel permeation chromatography with triple detection system. Results: The methodological evaluation showed that this method had good specificity,precision,and repeatability. For Glucose,the linearity range was 0.001-0.02 mg·mL^-1(r=0.999 7,n=5),the limits of detection and quantification were 0.000 2 mg·mL^-1 and 0.000 67 mg·mL^-1. The average recoveries (n=6) were 93.6%,RSD=2.5%;For Sandostatin? LAR and self-made microspheres,the results of microspheres 1,microspheres 2 are basically identical to Sandostatin? LAR by the gel permeation chromatography with triple detection system and LC-MS/MS measurements. Conclusion: The LC-MS/MS analysis method for the determination of glucose content in Glu-PLGA is relatively convenient and simple with high accuracy and sensitivity. The gel permeation chromatography with triple detection system and LC-MS/MS methods can be used for qualitative and quantitative characterization of Glu-PLGA,which can provide reference for the future research of Glu-PLGA.

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