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通过亲水相互作用色谱-串联质谱联用对磷酰胺吗啉代寡聚物进行测序

Sequencing of Phosphorodiamidate Morpholino Oligomers by Hydrophilic Interaction Chromatography Coupled to Tandem Mass Spectrometry.

作者信息

Wang Mingming, O'Day Brian, Michaels Brian, Jurayj Jurjus, Cai Bao Zhong, Wei Tao

机构信息

Sarepta Therapeutics, Inc., Cambridge, Massachusetts 02142, United States.

出版信息

J Am Soc Mass Spectrom. 2024 Oct 2;35(10):2490-2498. doi: 10.1021/jasms.4c00281. Epub 2024 Aug 30.

DOI:10.1021/jasms.4c00281
PMID:39213635
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11450806/
Abstract

Sequencing of phosphorodiamidate morpholino oligomers (PMOs) by hydrophilic interaction chromatography (HILIC) coupled to tandem mass spectrometry (MS/MS) is reported. The MS/MS analysis was performed using a quadrupole/time-of-flight (Q-ToF) mass analyzer and collision induced dissociation (CID) in negative ion mode. To improve MS sensitivity in negative ion mode, HILIC conditions, including the separation column, mobile phases, and MS parameters, were optimized. Using the developed HILIC-CID-MS/MS method, 100% sequence coverage was achieved for PMOs ranging from 18-mer to 25-mer. Additionally, the method was successfully applied to identifying positional isomers of - 1 deletion impurities present in PMO drug substances.

摘要

报道了通过亲水相互作用色谱法（HILIC）与串联质谱法（MS/MS）联用对磷二酰胺吗啉代寡聚物（PMO）进行测序。MS/MS分析使用四极杆/飞行时间（Q-ToF）质谱仪并在负离子模式下进行碰撞诱导解离（CID）。为提高负离子模式下的质谱灵敏度，对HILIC条件进行了优化，包括分离柱、流动相和质谱参数。使用所开发的HILIC-CID-MS/MS方法，对于18聚体至25聚体的PMO实现了100%的序列覆盖。此外，该方法成功应用于鉴定PMO原料药中存在的-1缺失杂质的位置异构体。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c563/11450806/cfebb451934f/js4c00281_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c563/11450806/14331a6ecec3/js4c00281_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c563/11450806/c0ccc06e2192/js4c00281_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c563/11450806/37d018e6af6c/js4c00281_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c563/11450806/9cb2d64c9894/js4c00281_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c563/11450806/4cd32a317d02/js4c00281_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c563/11450806/cfebb451934f/js4c00281_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c563/11450806/14331a6ecec3/js4c00281_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c563/11450806/c0ccc06e2192/js4c00281_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c563/11450806/37d018e6af6c/js4c00281_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c563/11450806/9cb2d64c9894/js4c00281_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c563/11450806/4cd32a317d02/js4c00281_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c563/11450806/cfebb451934f/js4c00281_0006.jpg

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