| Author(s): |
Suvajyoti S. Guha; Joshua R. Wayment; Michael J. Tarlov; Michael R. Zachariah; |
| Title: |
Electrospray – Differential Mobility Analysis as an Orthogonal Tool to Size Exclusion Chromatography for Characterization of Protein Aggregates |
| Published: |
March 12, 2012 |
| Abstract: |
The biopharmaceutical industry characterizes and quantifies aggregation of protein therapeutics using multiple analytical techniques to cross validate results. Here we demonstrate the use of electrospray-differential mobility analysis (ES-DMA), a gas-phase and atmospheric pressure ion-mobility method for characterizing protein aggregates. Two immunoglobulins (IgGs) are systematically heat treated to induce aggregation and characterized using size exclusion chromatography (SEC) and ES-DMA. Although ES-DMA is a gas phase characterization method, we find that aggregation kinetic rate constants determined by ES-DMA to be in excellent agreement with those determined by SEC. It is also found that ES-DMA is more capable of resolving aggregates of IgGs than SEC. The higher resolution of ES-DMA and a limit of detection two orders of magnitude lower than the SEC potentially make it a powerful tool for characterization of nascent protein aggregates in the biopharmaceutical industry. |
| Citation: |
Journal of Pharmaceutical Sciences |
| Volume: |
101 |
| Issue: |
6 |
| Pages: |
pp. 1985 - 1994 |
| Keywords: |
immunoglobulins; heat-treat; ES-DMA; SEC; rate constant; protein aggregates |
| Research Areas: |
Electrospray Differential Mobility Analysis (ES-DMA), Nanotechnology, Characterization, Nanometrology, and Nanoscale Measurements |
| DOI: |
10.1002/jps.23097 (Note: May link to a non-U.S. Government webpage) |
| PDF version: |
 Click here to retrieve PDF version of paper (347KB) |
