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采用离子对反相液相色谱-质谱联用分析反义寡核苷酸及其代谢物。

Analysis of Antisense Oligonucleotides and Their Metabolites with the Use of Ion Pair Reversed-Phase Liquid Chromatography Coupled with Mass Spectrometry.

机构信息

a Chair of Environmental Chemistry and Bioanalytics, Faculty of Chemistry , Nicolaus Copernicus University , Toruń , Poland.

出版信息

Crit Rev Anal Chem. 2019;49(3):256-270. doi: 10.1080/10408347.2018.1517034. Epub 2019 Jan 5.

DOI:10.1080/10408347.2018.1517034
PMID:30612436
Abstract

Antisense oligonucleotides (ASOs) have been widely investigated as a potential drugs because of their ability to bind with the target DNA or RNA strands, which may lead to inhibition of translational processes. This review presents currently approved oligonucleotide (OGN) drugs and summarizes their modification types, mechanisms of action, and application of ion pair reversed phase liquid chromatography for the analysis. Special attention was paid to the stationary phases selection for the separation of OGNs and the impact of different compositions of mobile phases on retention and signal intensity in mass spectrometry (MS). Moreover, the application of ion pair liquid chromatography coupled with MS for the separation and determination of metabolites of ASOs was described. The type of matrix, time of analysis, lower limits of quantification and detection, as well as precision, accuracy, and linearity of developed methods have been included as part of this contribution.

摘要

反义寡核苷酸 (ASO) 因其能够与靶 DNA 或 RNA 链结合,从而可能抑制翻译过程,因此被广泛研究作为一种潜在药物。本综述介绍了目前批准的寡核苷酸 (OGN) 药物,并总结了它们的修饰类型、作用机制,以及用于分析的离子对反相液相色谱法的应用。特别关注了用于分离 OGN 的固定相选择,以及流动相组成对质谱 (MS) 中保留和信号强度的影响。此外,还描述了离子对液相色谱法与 MS 联用在 ASO 代谢物的分离和测定中的应用。该综述涵盖了方法的开发中所涉及的基质类型、分析时间、定量和检测下限,以及精密度、准确度和线性度。

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