發(fā)布時間：2018-02-28 12:08

  本文關(guān)鍵詞： 貝伐珠單抗 糖基化修飾 液相色譜-串聯(lián)質(zhì)譜聯(lián)用 平行反應(yīng)監(jiān)測 藥代動力學(xué)　出處：《分析化學(xué)》2017年11期 　論文類型：期刊論文

【摘要】：利用基質(zhì)輔助激光解析電離飛行時間質(zhì)譜技術(shù)、SDS-聚丙烯酰胺凝膠電泳技術(shù)以及Shot-gun蛋白質(zhì)組學(xué)策略對貝伐珠單克隆抗體藥物及其糖基化修飾進(jìn)行了全面表征,共發(fā)現(xiàn)17種糖型并確定了特征肽段序列。利用液相色譜-串聯(lián)質(zhì)譜聯(lián)用技術(shù),采用平行反應(yīng)檢測模式,通過測定單抗水解后產(chǎn)生的特征肽段,實現(xiàn)了對大鼠血漿樣品中單抗藥物含量的絕對定量分析,獲得不同給藥計量下的貝伐珠單抗的藥物濃度-時間曲線,同時實現(xiàn)了對單抗糖基化修飾各糖型的相對定量分析。本實驗首先建立標(biāo)準(zhǔn)工作曲線,對大鼠血漿樣品中的貝伐珠單抗進(jìn)行定量分析,在線性范圍內(nèi),相關(guān)系數(shù)R2=0.998,定量限為66 fmol,線性關(guān)系良好。對大鼠血漿樣品的測定結(jié)果表明,高、低計量給藥的貝伐珠單抗藥物濃度-時間曲線趨勢基本一致,濃度均為直接下降,與理論趨勢相符。但是大多數(shù)糖型呈現(xiàn)濃度先上升的現(xiàn)象,之后的代謝情況因糖型差異而有所不同。
[Abstract]:Using matrix assisted laser desorption ionization time of flight mass spectrometry and SDS- polyacrylamide gel electrophoresis and Shot-gun proteomics strategy, the bevacious monoclonal antibody drugs and their glycosylation modification were characterized. A total of 17 carbohydrates were found and the characteristic peptide segments were sequenced. By using liquid chromatography-tandem mass spectrometry (LC-MS) and parallel reaction detection mode, the characteristic peptides produced by hydrolysis of McAbs were determined. The absolute quantitative analysis of the content of monoclonal antibodies in rat plasma samples was achieved, and the concentration-time curves of bevacizumab in different dosages were obtained. At the same time, the relative quantitative analysis of each sugar type modified by glycosylation of monoclonal antibody was realized. In this experiment, the standard working curve was established, and the bevacizumab in rat plasma was quantitatively analyzed in a linear range. The correlation coefficient was 0.998, the quantitative limit was 66fmol, and the linear relationship was good. The results of determination of plasma samples from rats showed that the concentration-time curves of bevacizumab with high and low doses were basically the same, and the concentrations were all decreased directly. But the concentration of most sugars increased first, and then the metabolism was different according to the difference of sugar type.
【作者單位】： 吉林大學(xué)生命科學(xué)學(xué)院;中國科學(xué)院大連化學(xué)物理研究所 中國科學(xué)院分離分析化學(xué)重點實驗室;
【基金】：國家自然科學(xué)基金項目(No.81373374)資助~~
【分類號】：O657.63;TQ450.1

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