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The quantitation of therapeutic olingonucleotides and their impurities analysed using hyphenated liquid chromatography and mass spectrometry

The quantitation of therapeutic olingonucleotides and their impurities analysed using hyphenated liquid chromatography and mass spectrometry
The quantitation of therapeutic olingonucleotides and their impurities analysed using hyphenated liquid chromatography and mass spectrometry
As demand for therapeutic oligonucleotide drugs to treat a wider range of conditions increases, there is a requirement for a robust method for the quantitation of the impurities within a drug product. The development of a method that can be employed across all laboratories, regardless of the Liquid chromatography – Mass spectrometry instrumentation used, is highly desirable to ensure consistency of testing and to confirm inter-batch variation.

Factors influencing the reliability of quantitation have been investigated, including mobile phase additives, mass analyser type and in-source collision-induced dissociation voltage. Strategies for quantitating the data collected have also been considered and compared. The effect of the oligonucleotide sequence on the level of in-source fragmentation has been observed and discussed.

Recommendations are made for the most appropriate mobile phase reagents, mass analyser type and method of quantitation to be used to allow the development of an analytical method for use across laboratories to accurately and precisely quantitate therapeutic oligonucleotides and their impurities.
University of Southampton
Powley, Stephanie Louise
82bb21a3-348f-40b0-b387-439655fbba82
Powley, Stephanie Louise
82bb21a3-348f-40b0-b387-439655fbba82
Langley, Graham
7ac80d61-b91d-4261-ad17-255f94ea21ea

Powley, Stephanie Louise (2018) The quantitation of therapeutic olingonucleotides and their impurities analysed using hyphenated liquid chromatography and mass spectrometry. University of Southampton, Doctoral Thesis, 214pp.

Record type: Thesis (Doctoral)

Abstract

As demand for therapeutic oligonucleotide drugs to treat a wider range of conditions increases, there is a requirement for a robust method for the quantitation of the impurities within a drug product. The development of a method that can be employed across all laboratories, regardless of the Liquid chromatography – Mass spectrometry instrumentation used, is highly desirable to ensure consistency of testing and to confirm inter-batch variation.

Factors influencing the reliability of quantitation have been investigated, including mobile phase additives, mass analyser type and in-source collision-induced dissociation voltage. Strategies for quantitating the data collected have also been considered and compared. The effect of the oligonucleotide sequence on the level of in-source fragmentation has been observed and discussed.

Recommendations are made for the most appropriate mobile phase reagents, mass analyser type and method of quantitation to be used to allow the development of an analytical method for use across laboratories to accurately and precisely quantitate therapeutic oligonucleotides and their impurities.

Text
S. Powley Thesis final - Version of Record
Available under License University of Southampton Thesis Licence.
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More information

Published date: May 2018

Identifiers

Local EPrints ID: 422228
URI: http://eprints.soton.ac.uk/id/eprint/422228
PURE UUID: 5a8fcf34-07ea-449b-b3f0-ba838dcc47f9
ORCID for Stephanie Louise Powley: ORCID iD orcid.org/0000-0003-3914-0580
ORCID for Graham Langley: ORCID iD orcid.org/0000-0002-8323-7235

Catalogue record

Date deposited: 19 Jul 2018 16:30
Last modified: 28 Jun 2021 04:01

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Contributors

Author: Stephanie Louise Powley ORCID iD
Thesis advisor: Graham Langley ORCID iD

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