Avondlezing door Dr. T. de Boer georganiseerd door de Groningse Chemische Kring.
Advanced Analyses of Biomolecules – new generation of oncolytics
Samenvatting
In this presentation, the bioanalytical challenges in developing novel drug delivery systems will be discussed and solutions will be explored to overcome these challenges. The focus will be on nanomedicines and anti-body drug conjugates. Ardena is a fully integrated contract development and manufacturing organization (CDMO) as well as a fully integrated contract research organization (CRO). Ardena is globally recognized as a leader in the development and manufacture of advanced drug delivery systems based on nanoparticles.
At Ardena Bioanalysis in Assen we offer a full range of bioanalytical services, catering to both non-regulated early drug discovery and regulated pre-clinical and clinical phases. Our expertise extends across various types of drug products and biomarkers, including small molecules, proteins (including antibodies, antibody-drug conjugates, and oligonucleotides), and more.
Two case studies will be discussed. The first study concerns the determination of an antibody drug conjugate (ADC) in human plasma using an ultra-high performance liquid chromatography system hyphenated with a tandem mass-spectrometer (LC-MS/MS) instead of a conventional Enzyme-Linked Immuno-Sorbent Assay (ELISA) and the second study concerns the analysis of a polypeptide-functionalized superparamagnetic iron oxide nanoparticle in plasma and tissue.
The analysis of complex molecules like ADCs and nanoparticles in a complex matrix as plasma or tissue is challenged by the limitations of the equipment used for the analysis. In our laboratory we have 18 highly sensitive tandem mass spectrometers. Although these machines offer the required sensitivity, they are limited in the fact that large molecules like ADCs and nanoparticles cannot be analyzed intact. An ADC consists of a toxin attached to an antibody via a cleavable linker. This implies that besides the total AB content also the conjugated AB content and the concentration of the free toxin must be quantified. Furthermore, the undesired release of the toxin during sample collection, sample handling and sample storage should be studied. As triple quad MS systems are unable to analyze the ADC intact, the antibody must be enzymatically cleaved to obtain representative signature peptides. The nanoparticle discussed during the presentation consists of multiple peptides attached via a polymer linker to an iron oxide core. In this case besides the iron content and the polymer content also the free and bound peptides need to be quantified. Similar to the ADC, the peptides need to be cleaved from the polymer linker via tryptic digestion.
As both studies were submitted to the authorities for approval, the studies were conducted in a laboratory with GLP accreditation, and the bioanalysis was conducted according to international guidelines (ICH-M10).
Achtergrond van Dr. Theo de Boer
Ing. (BSc), Hoger Laboratorium Onderwijs (Leeuwarden)
Drs. (MSc), Farmacie (RUG, Groningen)
Dr. (PhD), Analytische Chemie en Toxicologie (Farmacie, RUG, Groningen)
Loopbaan:
- 2000 – 2001: Haemoprobe (Groningen) – Manager operations
- 2001 - 2003: Merska (Groningen) – Manager operations
- 2003 – 2012: Xendo/ QPS (Groningen) - Manager Bioanalytical & Scientific affairs
- 2012 - 2013: Eurofins Food (Heerenveen) - BU manager
- 2013 – nu: ABL/Ardena Bioanalysis (Assen) - Scientific Director LC-MS/MS
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Stuur daartoe een mail naar gck@kncv.nl of kommer.brunt@planet.nl.
