title: Electrospray-differential mobility analysis as an orthogonal tool to size-exclusion chromatography for characterization of protein aggregates.
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 immunoglobulin Gs 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 is in good agreement with those determined by SEC. ES-DMA appears to have a higher resolution and lower limit of detection as compared with SEC. Thus, ES-DMA can potentially become an important orthogonal tool for characterization of nascent protein aggregates in the biopharmaceutical industry.
authors.affiliation: National Institute of Standards and Technology, Gaithersburg, Maryland 20899, USA.
authors.forename: Suvajyoti
authors.initials: S
authors.lastname: Guha
authors.forename: Joshua R
authors.initials: JR
authors.lastname: Wayment
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Tarlov
authors.forename: Michael R
authors.initials: MR
authors.lastname: Zachariah
mesh_terms: D002850:Chromatography, Gel / Q000379:methods*; D011506:Proteins / Q000737:chemistry*
chemical_list: D011506:Proteins