Title
Bioanalytical LC-MS/MS of protein-based biopharmaceuticals
Author
van den Broek, I.
Niessen, W.M.A.
van Dongen, W.D.
Publication year
2013
Abstract
Biotechnology increasingly delivers highly promising protein-based biopharmaceutical candidates to the drug development funnel. For successful biopharmaceutical drug development, reliable bioanalytical methods enabling quantification of drugs in biological fluids (plasma, urine, tissue, etc.) are required to generate toxicokinetic (TK), pharmacokinetic (PK), and bioavailability data. A clear observable trend is that liquid chromatography coupled to (tandem) mass spectrometry (LC-MS(/MS)) is more and more replacing ligand binding assays (LBA) for the bioanalytical determination of protein-based biopharmaceuticals in biological matrices, mainly due to improved selectivity and linear dynamic ranges. Practically all MS-based quantification methods for protein-based biopharmaceuticals traditionally rely on (targeted) proteomic techniques and include "seven critical factors": (1) internal standardization, (2) protein purification, (3) enzymatic digestion, (4) selection of signature peptide(s), (5) peptide purification, (6) liquid chromatographic separation and (7) mass spectrometric detection. For this purpose, the variety of applied strategies for all "seven critical factors" in current literature on MS-based protein quantification have been critically reviewed and evaluated. Special attention is paid to the quantification of therapeutic monoclonal antibodies (mAbs) in serum and plasma since this is a very promising and rapidly expanding group of biopharmaceuticals. Additionally, the review aims to predict the impact of strategies moving away from traditional protein cleavage isotope dilution mass spectrometry (PC-IDMS) toward approaches that are more dedicated to bioanalysis. © 2013 Elsevier B.V.
Subject
Triskelion BV
TARA - Toxicology and Risk Assessment
TNO Bedrijven
Biomedical Innovation
Biology
Healthy Living
Absolute quantification
Bioanalysis
LC-MS
Monoclonal antibodies
Sample preparation
Therapeutic protein
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DOI
https://doi.org/10.1016/j.jchromb.2013.04.030
TNO identifier
473186
ISSN
1570-0232
Source
Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, 929, 161-179
Document type
article