Evaluation of hydrophilic interaction liquid chromatography, capillary zone electrophoresis and drift tube ion-mobility quadrupole time of flight mass spectrometry for the characterization of phosphodiester and phosphorothioate oligonucleotides

Demelenne, Alice; Gou, Marie-Jia; Nys, Gwenaël; Parulski, Chloé; Crommen, Jacques; Servais, Anne-Catherine; Fillet, Marianne

doi:10.1016/j.chroma.2019.460716

Cited by 35 publications

(15 citation statements)

References 25 publications

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“…studied chemically modified and unmodified oligonucleotides using UHPLC‐drift tube ion‐mobility (DTIMS)‐Q‐TOF‐MS and capillary zone electrophoresis (CZE)‐DTIMS‐Q‐TOF‐MS, where through successful method development, both separation techniques showed strengths in their selectivity for both shortmers and longmers, while the DTIMS provided information about ion conformations and the Q‐TOF‐MS generated accurate mass measurements. DTIMS could determine with good accuracy the number of nucleotides in a given oligonucleotide, while the HRMS data provided the identity of the nucleotides 64 . This work could prove useful for medicinal oligonucleotide development and quality control.…”

Section: Post‐approval Analyses and Hrms Quantificationmentioning

confidence: 96%

Advances in high‐resolution mass spectrometry applied to pharmaceuticals in 2020: A whole new age of information

Géhin

Holman

2021

Analytical Science Advances

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Continuous improvements in mass spectrometry (MS) have resulted in the widespread availability and adoption of high‐resolution mass spectrometry (HRMS) across laboratories worldwide. The capabilities and the associated advantages of HRMS make it an invaluable analytical tool for analyte characterization, screening, and quantification methodologies for a wide scope of applications across pharmaceutical development. These applications include drug discovery, product characterizations of both small molecules and novel drug modalities, in vitro and in vivo metabolism studies, post‐approval quality control, and pharmacovigilance. This review gives an overview of the current capabilities of HRMS and its pharmaceutical applications in 2020, and provides a perspective on the future of HRMS within the pharmaceutical industry.

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Section: Post‐approval Analyses and Hrms Quantificationmentioning

confidence: 96%

Advances in high‐resolution mass spectrometry applied to pharmaceuticals in 2020: A whole new age of information

Géhin

Holman

2021

Analytical Science Advances

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“…This "bottoming-out"-shaped trend of the CCS values has been previously observed. 13,14,22 However, when the charge states S1 [supporting information]). Therefore, we consider that the differences in the confirmed coefficients of determination did not originate from low accuracy, but rather from the different physicochemical properties of the oligonucleotide.…”

Section: Collision Cross-section Calculationsmentioning

confidence: 99%

“…For example, it was found that simple differences in oligonucleotide sequence could be distinguished by TWIMS. 13 Moreover, an analysis of miRNAs showed that the secondary structure of oligonucleotides significantly affects their gas-phase ion mobility using three different self-complementary sequences. 14 A recent study using TWIMS revealed the interactions between alkylamine reagents and oligonucleotides by comparing several types of alkylamines, and the differences in anion adduction were confirmed.…”

Section: Introductionmentioning

confidence: 99%

“…The utility of the TWIMS for oligonucleotide analysis has been reported. For example, it was found that simple differences in oligonucleotide sequence could be distinguished by TWIMS 13 . Moreover, an analysis of miRNAs showed that the secondary structure of oligonucleotides significantly affects their gas‐phase ion mobility using three different self‐complementary sequences 14 .…”

Section: Introductionmentioning

confidence: 99%

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Physicochemical property evaluation of modified oligonucleotides by traveling‐wave ion mobility mass spectrometry

Omuro

Yamaguchi

Kawase³

et al. 2022

Rapid Comm Mass Spectrometry

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Rationale Therapeutic oligonucleotides have molecular weights of more than 6000 Da. They typically contain chemically modified structures such as phosphorothioate (PS) and a locked nucleic acid (LNA). To determine the effect of the length and chemical modification on the physicochemical properties, various nucleic acids with different lengths and modified structures were analyzed using traveling‐wave ion mobility mass spectrometry (TWIMS). Methods The physicochemical characteristics of the modified oligonucleotides were determined using IM‐MS. Each oligonucleotide was evaluated by confirming the multivalent charge state drift times, collision cross‐section (CCS) values, and CCS widths. Results By plotting the m/z for oligonucleotides of different lengths and the CCS values at each charge state, a bottoming‐out shape plot at one charge per 4.0–3.5 bases was confirmed. Moreover, significant differences were observed in the CCS values between the PS‐modified and unmodified oligonucleotides. The PS‐modified oligonucleotide showed a wider CCS range that was proportional to the PS modification ratio of the oligonucleotide sequence. Conclusions The TWIMS results showed a correlation between the length and modification of oligonucleotides and the CCS values. In addition, it suggested that each charge state of the oligonucleotide ion has different physicochemical properties.

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“…CZE coupled to MS was also used to estimate rate and equilibrium constant of the conformational dynamics of DNA G-Quadruplex 21 . More recently, Demelenne et al performed CZE-MS analysis in order to characterize therapeutic olignoculeotides 22 . Different geometries of interface were developed since the first CE-MS hyphenation 23 .…”

Section: Introductionmentioning

confidence: 99%

Characterization of Post-Transcriptional RNA Modifications by Sheathless Capillary Electrophoresis–High Resolution Mass Spectrometry

et al. 2020

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Since last decade there is a growing interest of RNA modifications analysis. High performance liquid chromatography-tandem mass spectrometry coupling (HPLC-MS/MS) is classically used to characterize post-transcriptional modifications of ribonucleic acids (RNAs). Here we proposed a novel and simple workflow based on capillary zone electrophoresis-tandem mass spectrometry (CE-MS/MS), in positive mode, to characterize RNA modifications at nucleoside and oligonucleotide levels. A first total digestion of purified RNA, prior CE-MS/MS analysis, enables to identify nucleoside modifications. Then, using a bottom-up approach, sequencing of RNAs and mapping of modifications were performed. Sequence coverages from 68% to 97% were obtained for four tRNAs. Furthermore, unambiguous identification and mapping of several modifications were achieved.

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Evaluation of hydrophilic interaction liquid chromatography, capillary zone electrophoresis and drift tube ion-mobility quadrupole time of flight mass spectrometry for the characterization of phosphodiester and phosphorothioate oligonucleotides

Cited by 35 publications

References 25 publications

Advances in high‐resolution mass spectrometry applied to pharmaceuticals in 2020: A whole new age of information

Advances in high‐resolution mass spectrometry applied to pharmaceuticals in 2020: A whole new age of information

Physicochemical property evaluation of modified oligonucleotides by traveling‐wave ion mobility mass spectrometry

Characterization of Post-Transcriptional RNA Modifications by Sheathless Capillary Electrophoresis–High Resolution Mass Spectrometry

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