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A Rapid, Automated LC-MS Assay for Analysis of Methionine Oxidation in Therapeutic mAbs Logo
  • Abstract
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Company Biography

Methionine oxidation is considered a critical quality attribute (CQA) of therapeutic antibodies and may impact the clinical safety and efficacy of the final drug product. Therefore, monitoring of methionine oxidations is required during the discovery, development, and production of therapeutic antibodies. Traditional methods to characterize oxidation rely on tryptic peptide mapping and LC-MS, a labor intensive and time-consuming process that generates large data sets and requires trained and skilled manual interpretations. Middle-level analysis provides a faster and simpler alternative by combining minimal sample preparation with short analysis time. It entails the digestion of the mAb at one specific site below the hinge using the FabRICATOR protease which – after reduction of disulfide bonds – yields three subunits of 23-25 kDa in size. These are well suited for analysis by LC-MS for the quantification of many different CQAs. Here, we present a rapid LC-MS assay for antibody oxidation analysis at the middle level. It is based on a 30 minute one-pot digestion/reduction using and FabRICATOR and GlycINATOR followed by reverse-phase LC-MS on a Waters BioAccord system with a run time of only 15 minutes per sample. All sample preparations were performed in an automated fashion using an Andrew+ liquid handling robot (Waters). Using this assay, we were able to reliably quantify methionine oxidation in a panel of different commercial mAb that had undergone forced oxidation. No method optimization was necessary to run mAbs of different subclasses, making this a platform method applicable to many different samples. The short analysis time, simple data interpretation and the possibility for automation of sample preparation make this assay ideally suited for high volume applications such as stability studies or formulation optimization.

Contact Information

Name
Kevin Cook
Email
kevin.cook@genovis.com

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Team Members

Kevin Cook profile image

Kevin Cook

Genovis, Inc.

Presenter
Kevin Cook
Kevin Cook Icon
Genovis, Inc.
Email: kevin.cook@genovis.com
Andreas Nägeli profile image

Andreas Nägeli

Genovis AB

Co-Author
Andreas Nägeli
Andreas Nägeli Icon
Genovis AB
Email: andreas.nageli@genovis.com
Erica Andersson profile image

Erica Andersson

Genovis AB

Co-Author
Erica Andersson
Genovis AB
Email: erica.andersson@genovis.com
Andrea Persson profile image

Andrea Persson

Genovis AB

Co-Author
Andrea Persson
Genovis AB
Email: andrea.persson@genovis.com
Jonathan Sjogren profile image

Jonathan Sjogren

Genovis AB

Co-Author
Jonathan Sjogren
Genovis AB
Email: jonathan.sjogren@genovis.com
Helén Nyhlén profile image

Helén Nyhlén

Genovis AB

Co-Author
Helén Nyhlén
Genovis AB
Email: helen.nyhlen@genovis.com