An evaluation of instrument types for mass spectrometry-based multi-attribute analysis of biotherapeutics.
Zhongqi ZhangPik K ChanJason RichardsonBhavana ShahPublished in: mAbs (2021)
Multi-attribute methods (MAM), based on proteolytic digestion followed by liquid chromatography-mass spectrometry analysis of proteolytic peptides, have gained substantial attention in the biopharmaceutical industry for quantifying a variety of quality attributes for therapeutic proteins. Most MAM developed so far have been based on high-resolution mass spectrometers, due to their superb resolving power to distinguish analyte signals from interferences. Lower-resolution instruments, if demonstrated suitable, may further promote the adoption of the technology due to their low cost, small footprint, and ease of use. In this work, we compared the performance of a high-resolution instrument with a few low-resolution quadrupole-type instruments in quantifying a diverse set of quality attributes in a monoclonal antibody product. Different modes of operation for the quadrupole instruments, including scan mode, selected-ion monitoring and multiple-reaction monitoring, were evaluated. The high-resolution instrument has superb performance, with a quantitation limit of 0.002%. Single-quadrupole instruments in scan mode, on the other hand, provide a quantitation limit of about 1%, which may be fit-for-purpose for many routine MAM applications.
Keyphrases
- mass spectrometry
- liquid chromatography
- high resolution
- patient reported outcomes
- tandem mass spectrometry
- high resolution mass spectrometry
- monoclonal antibody
- high performance liquid chromatography
- low cost
- gas chromatography
- capillary electrophoresis
- simultaneous determination
- computed tomography
- solid phase extraction
- single molecule
- quality improvement
- electronic health record
- magnetic resonance imaging
- clinical practice
- high speed
- liquid chromatography tandem mass spectrometry