Native Intact Mass Analysis
Get deep structural insight to complex proteins and protein interactions
The complexity of modern therapeutic proteins, such as antibody-drug conjugates (ADCs), presents a significant analytical challenge requiring high resolution chromatography combined with high resolution mass spectrometry. ADCs involving cysteine conjugation present a unique challenge for characterization as proper intact analysis requires native mass spectrometry conditions to preserve structurally-critical non-covalent binding between antibody chains. Intact protein analysis under native mass spectrometric conditions can now be performed routinely using mass spec friendlily buffers together with size exclusion (SEC) or ion exchange chromatography (IEC) coupled to Q Exactive BioPharma series mass spectrometers.
Native intact mass analysis workflow
Native intact mass analysis categories
Use Thermo Scientific MAbPac SEC-1 Size Exclusion Columns for high-resolution separation of monoclonal antibody (mAb) analysis, including monomers and aggregates. These size-exclusion chromatography (SEC) columns provide superior performance, under non-denaturing conditions, and in high- and low-salt mobile phases and volatile eluents.
Use the innovative architecture of a UHPLC system that has been tailored to the specific and demanding analytical requirements that these essential drugs impose. The Thermo Scientific Vanquish Flex Binary and Quaternary systems have been designed and manufactured to exacting engineering standards to be truly built for biopharma.
The BioPharma Option for the Thermo Scientific Q Exactive Plus and Q Exactive HF Hybrid Quadrupole-Orbitrap mass spectrometers provides a complete BioPharma characterization solution. With the introduction of the high mass range (HMR) mode the platform is optimized for both conventional intact monoclonal antibody analysis performed in denaturing conditions, as well as native MS analysis which is ideal for antibody drug conjugates and other heterogeneous antibody samples.
While analysis of denatured proteins may be the most common LC/MS protein analysis, many biopharmaceutical and biological research applications require the analysis of protein-protein interactions and protein conformations in their native (non-denatured) state. An outstanding tool for investigating the higher order structure, native-like tertiary and quaternary protein structures is the new Thermo Scientific Q Exactive UHMR, which combines unsurpassed high resolution accurate mass Thermo Scientific Orbitrap analysis with an ability to analyze ultrahigh mass range up to 80,000 m/z.
BioPharma Finder integrated software provides confident protein deconvolution to determine the molecular weight of proteins in both denaturing and native conditions. Protein sequence matching identifies N-linked glycosylation and other common post-translational modifications (PTMs) via intact mass analysis, helping you to fully understand the heterogeneity of your biologic drug.
Three ways to spend less and get more
Upgrade your ability to achieve new scientific discoveries faster with Thermo Scientific Orbitrap mass analyzers that set new standards in sensitivity, performance and productivity. Or take advantage of upgrades to extend your current Thermo Scientific LC-MS system capabilities.
Join experts from Genentech and Thermo Fisher to get great structural insight into your drug product using the Q Exactive BioPharma platform of mass spectrometers.