Overview
It is estimated that over 70% of all recombinant protein biopharmaceuticals, and virtually all monoclonal antibodies, are glycosylated, meaning that one or more of the amino acids in their structure are modified with a glycan (a branched chain of multiple sugar moieties). While the glycosylation profile of a biopharmaceutical is known to have a significant impact on its efficacy, pharmacokinetics, stability and immunogenicity, and is therefore extensively characterised during development and manufacturing, glycosylation has traditionally received less attention in the field of quantitative bioanalysis. As a result, changes in the in vivo glycosylation profile of a biopharmaceutical following administration are often poorly understood, and how these glycosylation patterns evolve over time in circulation frequently remains unknown.
One of the reasons for this stems from the inherent complexity of therapeutic glycoproteins. These molecules often display extensive structural heterogeneity due to variations in glycosylation site occupancy and the presence of multiple glycan structures at individual sites. Conventional bioanalytical methods typically determine total drug concentrations without differentiating between individual glycoforms, potentially overlooking important differences in their in vivo behaviour. An analytical approach that takes this heterogeneity into account is therefore essential. Liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS) enables the simultaneous, mass-selective detection of a large number of glycosylated peptides. When combined with the isolation of the therapeutic protein from plasma and enzymatic digestion, this approach allows individual glycoforms to be monitored within complex clinical samples.
During this webinar hosted by Bioanalysis Zone we will:
- Explore the fundamentals of protein glycosylation and its critical role in the development, efficacy, safety, and clinical performance of biopharmaceuticals.
- Present an LC-HRMS-based bioanalytical workflow for the isolation, characterization, and semi-quantitative monitoring of individual glycopeptides from therapeutic proteins in plasma.
- Demonstrate the application of this approach to pharmacokinetic analysis in a clinical trial of a therapeutic protein with seven glycosylation sites, highlighting how glycoform-resolved measurements can deliver insights beyond conventional total-drug quantification
Speakers:
Guinevere Lageveen-Kammeijer
Guinevere Lageveen-Kammeijer is Assistant Professor of Analytical Biochemistry at the University of Groningen, The Netherlands, where she leads the SUGAR Lab. Her research focuses on the development of ultrasensitive analytical methods for glycomics and glycoproteomics, with particular expertise in capillary electrophoresis–mass spectrometry (CE-MS). She develops and applies these technologies to characterise glycosylation in complex biological and clinical samples, with applications ranging from biomarker discovery and rare metabolic diseases to low-input and single-cell analysis and the detailed characterization of therapeutic glycoproteins. Guinevere obtained her Ph.D. in Analytical Chemistry from Leiden University Medical Center in 2019, where she investigated protein glycosylation in prostate cancer. She is the recipient of an NWO Veni grant and the ACS Rising Star Award and was named to The Analytical Scientist’s 2026 Top 40 Under 40 Power List.
Nico van de Merbel
Nico van de Merbel is Senior Director of Bioanalytical Science at ICON Laboratories in Assen, The Netherlands. With 35 years of experience in quantitative bioanalysis in academia and industry, his field of expertise is the bioanalytical application of chromatography – mass spectrometry methods for small and large molecules. He is responsible for research, method development and validation of LC-MS methods for biological samples. Nico obtained an M.Sc. in toxicology in 1990 and a Ph.D. in analytical chemistry in 1994 at the Free University in Amsterdam. He also holds an honorary professorship in Bioanalysis at the University of Groningen, where his research focuses on the quantitative use of LC-MS for bioanalysis of protein-based drugs and biomarkers.
Target Audience:
LC-MS scientists, managers and directors in academia and at pharmaceutical and biotech companies and contract research organizations.