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Quantitative analysis of dextran in rat plasma using Q-Orbitrap mass spectrometry based on all ion fragmentation strategy
Journal of Chromatography B ( IF 2.8 ) Pub Date : 2018-07-17 , DOI: 10.1016/j.jchromb.2018.07.015
Hao Wang , Honglei Chen , Jie Geng , Yi Zheng , Zhongyu Zhang , Lin Sun , Guihua Tai , Yifa Zhou

Dextran is a biocompatible glucose-based polymer that is widely used clinically as a plasma volume expander, anti-thrombotic agent, macromolecular carrier, peripheral blood flow enhancer, and artificial tears promoter. Because dextran has polydisperse molecular weights and tends to produce innumerable multi-charged precursor ions in the ion source, it is difficult to analysis this polymer using conventional liquid chromatography mass spectrometry. In this assay, all ion fragmentation strategy is used to solve this problem by allowing all dextran precursor ions generated in the ion source to enter the collision cell. Then serial dextran-specific fragments can be effectively generated from all precursor ions by higher energy collision dissociation and scanned by Orbitrap detector. These high resolution fragment ions provide high specificity and sensitivity for the quantitation of dextran in rat plasma. Here, we report a new quantitative method using size exclusion chromatography combined with Q Exactive mass spectrometry based on an all ion fragmentation strategy. Assay validation showed that this method is linear over the concentration range from 3 to 300 μg/mL. Our approach has been successfully applied to a pharmacokinetic study of dextran in rat and will promote the development of studies with other polysaccharides.



中文翻译:

基于全离子裂解策略的Q-Orbitrap质谱定量分析大鼠血浆中的右旋糖酐

葡聚糖是一种生物相容性葡萄糖基聚合物,在临床上广泛用作血浆容量增加剂,抗血栓形成剂,大分子载体,外周血流量增强剂和人工泪液促进剂。因为右旋糖酐具有多分散的分子量,并且倾向于在离子源中产生无数的多电荷前体离子,所以难以使用常规液相色谱质谱法分析该聚合物。在该分析中,所有离子碎片化策略都通过允许离子源中生成的所有右旋糖酐前体离子进入碰撞池来解决此问题。然后可以通过更高的能量碰撞解离作用从所有前体离子有效生成系列右旋糖酐特异性片段,并通过Orbitrap检测器进行扫描。这些高分辨率碎片离子为定量大鼠血浆中的葡聚糖提供了高特异性和灵敏度。在这里,我们报告了一种基于全离子碎裂策略的结合体积排阻色谱和Q Exactive质谱联用的新定量方法。分析验证表明,该方法在3至300μg/ mL的浓度范围内是线性的。我们的方法已经成功地应用于大鼠右旋糖酐的药代动力学研究,并将促进与其他多糖的研究进展。分析验证表明,该方法在3至300μg/ mL的浓度范围内是线性的。我们的方法已经成功地应用于大鼠右旋糖酐的药代动力学研究,并将促进与其他多糖的研究进展。分析验证表明,该方法在3至300μg/ mL的浓度范围内是线性的。我们的方法已经成功地应用于大鼠右旋糖酐的药代动力学研究,并将促进与其他多糖的研究进展。

更新日期:2018-07-17
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