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Biopharmaceutical development is booming and now an integral part of many pharmaceutical company pipelines. While these emerging biologics present exciting opportunities for the industry, their sophistication is challenging the limits of characterization at all stages of discovery and development.

The quantitation of proteins using the surrogate peptide approach can complicate nominal mass Triple Quadrupole MRM measurements due to co-extracted interference when using non-selective extraction techniques such as pellet digestion. High resolution coupled with accurate mass filtering can mitigate such interference, as reported previously for the determination of rituximab using the TripleTOF 6600 (Protein Quant Approaches). However, an additional level of selectivity can often be achieved on nominal mass systems using the orthogonal gas-phase separation approach offered by the SelexION+® Differential Mobility System technology (DMS). Interfaced between the sampling orifice and ion source, the DMS separates ions based upon differences in their migration rates under alternating low and high field waveform amplitudes (Figure 1). Ion clustering in low fields and declustering in high fields amplifies the distinction in mobility of an ion, resulting in improved resolution from interfering species of differing molecular cross-section.1-4

The number of protein based drugs coming onto the market is at an all-time high, particularly those produced with a host cell system. With host cells come their own proteins. These host cell proteins (HCPs) constitute a major part of process-related impurities and can adversely affect drug safety, so it is critical that they are identified and quantified accurately.

Characterization and quantification of host cell proteins (HCPs) in biopharmaceutical development and manufacturing is a critical step to ensuring product safety. While this can be achieved using ELISA, mass spectrometry using the SCIEX TripleTOF® 6600 System is more specific and enables the identification and quantitation of each of the individual proteins present.

When developing new quantitative assays for Biotherapeutics, every biologic requires a specific sample prep strategy, which includes sourcing reagents and research protocols. However, as every bioanalytical lab knows all too well, it can also take up to two months to develop an optimized and robust LC-MS assay. For this reason, researchers understandably want an easier way to develop highly sensitive and specific assays for biotherapeutics and biosimilars to accelerate sample turnaround time.

From small ions like phosphate, herbicide degradation to metabolites, oligosaccharides, peptides, and proteins. How is your lab analyzing polar molecules? The reason I ask is there is a saying, if you have a charged or polar molecule, look to capillary electrophoresis (CE) first. While liquid chromatography (LC) is an ideal front-end separation tool for many types of molecules, as the following poster points out, “From Small to Very Large, Orthogonal, Sensitive Polar Molecule Analysis by CESI-MS,” there are some situations that call for CE over LC analysis. For those of you that are not familiar with CESI-MS, it is the combining of CE separation with electrospray ionization, into one dynamic process, within the same device.

Quantitation of monoclonal antibodies (mAbs) in biological fluids is important during all stages of antibody drug development. First developed in the 1970s, therapeutic mAbs have both research and medicinal impact as they can be used for diagnosis and treatment of a wide variety of diseases, and have a high level of specificity.

In an effort to Replace, Refine, and Reduce the number of animals used for pre-clinical research, several microsampling strategies have been implemented which allow for the consolidation of satellite TK and main study groups. In addition to the ethical gains driven by these 3Rs, microsampling has the potential of increasing scientific value since it becomes feasible to directly correlate exposure, toxicological effects and pharmacological response in the same individual

Is your mind swimming with large molecule catabolism data? Do you spend hours manually processing through complex spreadsheets to match your data with theoretical biologic catabolites? Are you wasting precious time by drawing out and processing your therapeutic peptide as a small molecule? Are you worried that you could be missing something?

There is a lot of talk going around in the lab, and it has to do with the newly released Fast Glycan Labeling and Analysis technology. Where once research analysts needed to set aside days to perform glycan analysis, now takes an hour or so. Glycans are immediately identified by the software – so no need for data interpretation. That’s up to 5x faster than HILIC.

Did you know the X500B QTOF system makes point and click workflows for Biologics Characterization possible on your mass spectrometer? The newly-designed SCIEX OS software interface brings to life fluid navigation and ease of use so you can keep moving forward on your scientific discoveries. In fact, it’s so simple to learn and operate that you and your team can be up and running faster than you might expect.

Learning a new mass spec system can be a daunting task. Aside from the opportunity costs of training new users, you might face the hassle of downtime, and the wait to get expert help when needed. The X500B QTOF system puts a new spin on biologics characterization workflows because it is so easy to learn and operate that you can be up and running much faster than you expect. Powerful new software tools dramatically streamline method development and data processing, to enable everyone in your lab to get expert results. It’s fast because it’s easy, even for new users.

Have you ever wished for a compact instrument that delivers expert-level answers to your most complex biotherapeutic characterization challenges faster and easier than what you are doing now? At SCIEX, we recognize that even expert users want easier ways to perform daily characterization tasks and get great results every time. That’s why we set out to develop the X500B QTOF system: a robust and reliable new instrument and software solution that reduces complexity and simplifies biologics characterization workflows so every scientist can get expert-level results

Protein-based biotherapeutics, including monoclonal antibodies (mAbs) and antibody-drug conjugates (ADCs) are a growing component of pharmaceutical companies’ drug pipelines. The growth of ADCs in particular is due to their ability to selectivity target and deliver a potent molecule to a cancer cell based on a specific tumor marker. In order to support this growing class of new drug molecules, robust and reliable bioanalytical methods are required. While ligand binding assays (LBAs) like ELISA have been the most popular platform for biotherapeutic quantitation, bioanalytical scientists have been increasingly adopting hybrid LBA/LC-MS methods in this area.

Throughout all stages of development and manufacture, monoclonal antibodies (mAbs) exhibit a great deal of structural complexity. After translation and folding, proteins undergo post-translational modifications, as well as spontaneous and enzymatic degradation, such that a single preparation of purified mAb exhibits a range of small structural changes, composed of various glycoforms and charge variants, as well as amino acids alterations due to oxidation, deamidation, isomerization, or other chemical reactions. This display of structural heterogeneity can influence the overall stability, efficacy, and safety profile; therefore, understanding the extent of structural modifications has become extremely important to drug manufacturers who continually assess mAb composition throughout bioprocessing to demonstrate stability, batch-to-batch consistency, and long-term shelf life.