Separation of phosphorothioated oligonucleotide diastereomers using multiplexed drift tube ion mobility mass spectrometry.

Demelenne, Alice; Nys, Gwenael; Nix, Cindy; Fjeldsted, John C; Crommen, Jacques; Fillet, Marianne

doi:10.1016/j.aca.2021.339297

Article (Scientific journals)

Separation of phosphorothioated oligonucleotide diastereomers using multiplexed drift tube ion mobility mass spectrometry.

Demelenne, Alice; Nys, Gwenael; Nix, Cindy et al.

2022 • In Analytica Chimica Acta, 1191, p. 339297

Peer Reviewed verified by ORBi

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https://hdl.handle.net/2268/302382

DOI
10.1016/j.aca.2021.339297

PubMed
35033277

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Keywords :

Drift tube; Multiplexing; Oligonucleotides; Mass Spectrometry; Ion Mobility Spectrometry; Collision cross sections; Diastereomers

Abstract :

[en] Hydrophilic interaction liquid chromatography (HILIC) coupled to drift tube ion mobility spectrometry (DTIMS) was used to separate diastereomers of five-unit oligonucleotides containing 0, 1, 2 or 3 phosphorothioate (PS) linkages. Multiplexed DTIMS (where ions are pulsed into the drift tube according to a pre-encoded sequence) and post-acquisition processing using an innovative demultiplexing tool were investigated. The electric field inside the drift tube was optimized to achieve the highest resolving power. The entrance voltage providing the best two-peak resolution was -1000V with 3-bit multiplexing. Under optimized conditions, the eight diastereomers of an oligonucleotide with three PS linkages (5'-TC∗G∗T∗G-3') could be separated unambiguously. Indeed, those diastereomers differed in their collision cross section (CCS) values. The minimal CCS values difference between two adjacent diastereomers was 0.9% with maximal RSD on CCS values of 0.3%. The use of multiplexed ion mobility and the novel high-resolution demultiplexing tool represents a real breakthrough for resolution enhancement of diastereomers in linear DTIMS.

Disciplines :

Pharmacy, pharmacology & toxicology

Author, co-author :

Demelenne, Alice ; Université de Liège - ULiège > Université de Liège - ULiège

Nys, Gwenael ; Laboratory for the Analysis of Medicines, Center for Interdisciplinary Research on Medicines (CIRM), University of Liege, Quartier Hôpital, Avenue Hippocrate 15, 4000, Liege, Belgium

Nix, Cindy ; Université de Liège - ULiège > Département de pharmacie > Analyse des médicaments

Fjeldsted, John C; Agilent Technologies, Santa Clara, CA, 95051, United States

Crommen, Jacques ; Université de Liège - ULiège > Département de pharmacie

Fillet, Marianne ; Université de Liège - ULiège > Département de pharmacie > Analyse des médicaments

Language :

English

Title :

Separation of phosphorothioated oligonucleotide diastereomers using multiplexed drift tube ion mobility mass spectrometry.

Publication date :

25 January 2022

Journal title :

Analytica Chimica Acta

ISSN :

0003-2670

eISSN :

1873-4324

Publisher :

Elsevier B.V., Netherlands

Volume :

1191

Pages :

339297

Peer reviewed :

Peer Reviewed verified by ORBi

Additional URL :

https://api.elsevier.com/content/article/PII:S0003267021011235?httpAccept=text/xml

Funding text :

Alice Demelenne: experiments, redaction. Gwenael Nys: support for the experiments relative to IMS and redaction reviewing. Cindy Nix: support for the experiments relative to IMS. John C. Fjeldsted: support for the experiments relative to IMS. Jacques Crommen: redaction reviewing. Marianne Fillet: study design, financial support, Supervision, redaction reviewing.

Available on ORBi :

since 08 May 2023

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