Investigation of native and aggregated therapeutic proteins in human plasma with asymmetrical flow field-flow fractionation and mass spectrometry
(2022) In Analytical and Bioanalytical Chemistry 414(29-30). p.8191-8200- Abstract
Physiochemical degradation of therapeutic proteins in vivo during plasma circulation after administration can have a detrimental effect on their efficacy and safety profile. During drug product development, in vivo animal studies are necessary to explore in vivo protein behaviour. However, these studies are very demanding and expensive, and the industry is working to decrease the number of in vivo studies. Consequently, there is considerable interest in the development of methods to pre-screen the behaviour of therapeutic proteins in vivo using in vitro analysis. In this work, asymmetrical flow field-flow fractionation (AF4) and liquid chromatography–mass spectrometry (LC-MS) were combined to develop a novel analytical methodology for... (More)
Physiochemical degradation of therapeutic proteins in vivo during plasma circulation after administration can have a detrimental effect on their efficacy and safety profile. During drug product development, in vivo animal studies are necessary to explore in vivo protein behaviour. However, these studies are very demanding and expensive, and the industry is working to decrease the number of in vivo studies. Consequently, there is considerable interest in the development of methods to pre-screen the behaviour of therapeutic proteins in vivo using in vitro analysis. In this work, asymmetrical flow field-flow fractionation (AF4) and liquid chromatography–mass spectrometry (LC-MS) were combined to develop a novel analytical methodology for predicting the behaviour of therapeutic proteins in vivo. The method was tested with two proteins, a monoclonal antibody and a serum albumin binding affibody. After incubation of the proteins in plasma, the method was successfully used to investigate and quantify serum albumin binding, analyse changes in monoclonal antibody size, and identify and quantify monoclonal antibody aggregates. Graphical abstract: [Figure not available: see fulltext.]
(Less)
- author
- Ramm, Ingrid LU ; Leeman, Mats ; Schagerlöf, Herje LU ; León, Ileana Rodríguez ; Castro, Alejandra and Nilsson, Lars LU
- organization
- publishing date
- 2022-12
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Aggregate, Antibody, Asymmetrical flow field-flow fractionation, Detection, Liquid chromatography–mass spectrometry, Plasma
- in
- Analytical and Bioanalytical Chemistry
- volume
- 414
- issue
- 29-30
- pages
- 10 pages
- publisher
- Springer
- external identifiers
-
- scopus:85139408265
- pmid:36198918
- ISSN
- 1618-2642
- DOI
- 10.1007/s00216-022-04355-2
- language
- English
- LU publication?
- yes
- id
- a37e4151-a1e4-4b2a-8897-6b90a04ae2d5
- date added to LUP
- 2022-12-19 12:57:47
- date last changed
- 2024-06-13 21:45:11
@article{a37e4151-a1e4-4b2a-8897-6b90a04ae2d5,
abstract = {{<p>Physiochemical degradation of therapeutic proteins in vivo during plasma circulation after administration can have a detrimental effect on their efficacy and safety profile. During drug product development, in vivo animal studies are necessary to explore in vivo protein behaviour. However, these studies are very demanding and expensive, and the industry is working to decrease the number of in vivo studies. Consequently, there is considerable interest in the development of methods to pre-screen the behaviour of therapeutic proteins in vivo using in vitro analysis. In this work, asymmetrical flow field-flow fractionation (AF4) and liquid chromatography–mass spectrometry (LC-MS) were combined to develop a novel analytical methodology for predicting the behaviour of therapeutic proteins in vivo. The method was tested with two proteins, a monoclonal antibody and a serum albumin binding affibody. After incubation of the proteins in plasma, the method was successfully used to investigate and quantify serum albumin binding, analyse changes in monoclonal antibody size, and identify and quantify monoclonal antibody aggregates. Graphical abstract: [Figure not available: see fulltext.]</p>}},
author = {{Ramm, Ingrid and Leeman, Mats and Schagerlöf, Herje and León, Ileana Rodríguez and Castro, Alejandra and Nilsson, Lars}},
issn = {{1618-2642}},
keywords = {{Aggregate; Antibody; Asymmetrical flow field-flow fractionation; Detection; Liquid chromatography–mass spectrometry; Plasma}},
language = {{eng}},
number = {{29-30}},
pages = {{8191--8200}},
publisher = {{Springer}},
series = {{Analytical and Bioanalytical Chemistry}},
title = {{Investigation of native and aggregated therapeutic proteins in human plasma with asymmetrical flow field-flow fractionation and mass spectrometry}},
url = {{http://dx.doi.org/10.1007/s00216-022-04355-2}},
doi = {{10.1007/s00216-022-04355-2}},
volume = {{414}},
year = {{2022}},
}