Large molecule analysis by LC-MS

Welcome to the Bioanalysis Zone Spotlight on Large molecule analysis by LC-MS!

In recent years there has been an increase in large-molecule therapeutics due to their target specificity, lower toxicity and higher potency, with many pharmaceutical companies now offering a vast portfolio of large-molecule drugs.

This increase in large-molecule therapeutics has been accompanied by an increase in the use of LC–MS. Even though LBA’s are still the gold standard for large-molecule quantification, LC–MS has many benefits, such as a broader linear dynamic range allowing for multiplexing. However, there are still a range of challenges associated with the use of LC–MS for these compounds.

During this Spotlight we will look at various examples of LC–MS assays for the bioanalysis of large molecules. We will also discuss the benefits and current drawbacks of the techniques.

 

Articles

LC–MS/MS multiplexed assay for the quantitation of a therapeutic protein BMS-986089 and the target protein Myostatin
Application of high-resolution MS for development of peptide and large-molecule drug candidates
Minimalistic sample preparation strategies for LC–MS quantification of large molecule biopharmaceuticals: a case study highlighting alpha-1 antitrypsin protein
Application of high-resolution MS in the quantification of a therapeutic monoclonal antibody in human plasma

Insights

Developments in LC-MS applications – A commentary by Faye Vazvaei on the recent LC-MS spotlight survey
Internal Standard Considerations for Protein Therapeutic Bioanalytical LC-MS/MS Assays
LC–MS quantification of protein drugs: validating LC–MS methods using pre-digestion immunocapture
Analytical considerations in peptide and protein bioanalysis
Video: APA 2015 – Reaching new heights in targeted quantitation with HRMS
Large molecule analysis by LC–MS survey infographic
Video: LC-MS bioanalysis of proteins via the surrogate peptide approach
Peptide and protein bioanalysis application notebook
Spotlight survey large molecule analysis by LC-MS

Webinar

Panel discussion on large molecule quantification by LC–MS
Panel discussion on peptide and large molecule analysis by LC-MS
Rapid method development techniques for chiral LC-MS applications

Interviews

Interview with Erin Chambers (Waters Corporation): Addressing challenges in Peptide and Protein bioanalysis
Interview with Roland Staack (Roche) on the nomenclature for large molecule assays recently developed at Roche

Resources

LC-MS quantification of Trastuzumab using pellet digestion and ProteinWorks eXpress Direct Digest Kits
Simple, standardized, and sensitive quantification of Bevacizumab (Avastin) using ProteinWorks eXpress Digest Kits
ProteinWorks Application Notebook
A generic kit-based approach for quantifying monoclonal antibody drugs through direct digestion of discovery study samples
Video: LC-MS bioanalysis of proteins via the surrogate peptide approach
Peptide and protein bioanalysis application notebook
High sensitivity quantification of Infliximab in rat plasma using a fast, standardized kit-based approach
Peptide bioanalysis – solution guide
Quantification of the antibody drug conjugate, trastuzumab emtansine, and the monocolonal antibody, trastuzumab in plasma using a generic kit-based approach
Rapid method development techniques for chiral LC-MS applications