– for QC of Protein Drugs
Mass spectrometry has been a critical tool for drug discovery and development since the advent of atmospheric pressure ionization sources (ESI and APCI) in the 1980s. As a mass spectrometry expert, I have been looking forward to the move of this technology into quality control for many years. Researchers at CDER posted an article on their work to evaluate a Multiple Attribute Method (MAM) for identification a therapeutic antibody drug product (rituximab) sourced from US or foreign manufacturers. The MAM is very similar to the technique known in mass spectrometry circles as Multiple Reaction Monitoring (MRM) or Multi-Ion Monitoring (MIM), which tracks the presence and abundance of product-specific ions formed and separated in the mass spectrometer to assess the identity of the primary component and any secondary analytes (impurities or degradants). The technique is very familiar to drug metabolism scientists who use it to identify drug metabolites in biological samples.
In the CDER article on the MAM, the authors discuss drug product sample preparation by digestion to create mixtures of smaller protein molecules. The digests are introduced into the mass spectrometer using liquid chromatography. In the mass spectrometer the molecules are first ionized (charged) and then separated in an electromagnetic field based on their mass and charge. The separated molecules are further fragmented in the mass spectrometer, and the fragments are counted by a detector and the instrument software converts these counts into a mass spectrum over time, or a mass chromatogram. The size of each peak in the mass spectrum is proportional to the amount of the fragment represented at its particular mass and charge. Using this Method, the researchers were able to distinguish between the different sources of rituximab and produced some evidence that the MAM could be used to determine the short- and long-term stability of the product. These stability studies are the subject of future planned work by the research team.
Text Copyright © 2018 Katrina Rogers