ArticlemAbs
New methods allowing the detection of protein aggregates: a case study on trastuzumab.
Article in mAbs. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 65 citations in OpenAlex.
- Antibody Aggregation: A Problem Within the Biopharmaceutical Industry and Its Role in AL Amyloidosis Disease.The protein journal · 2025Review
- Enhancing breadth and durability of humoral immune responses in non-human primates with an adjuvanted group 1 influenza hemagglutinin stem antigen.NPJ vaccines · 2023Article
- Evaluation of fluorescent dyes to measure protein aggregation within mammalian cell culture supernatants.Journal of chemical technology and biotechnology (Oxford, Oxfordshire : 1986) · 2018Article
- Endothelial nitric oxide synthase oxygenase on lipid nanodiscs: A nano-assembly reflecting native-like function of eNOS.Biochemical and biophysical research communications · 2017Article
- A new approach for generating bispecific antibodies based on a common light chain format and the stable architecture of human immunoglobulin GThe Journal of biological chemistry · 2017Article
- Microparticles and Nanoparticles Delivered in Intravenous Saline and in an Intravenous Solution of a Therapeutic Antibody Product.Journal of pharmaceutical sciences · 2017Article
- Factors Governing the Precision of Subvisible Particle Measurement Methods - A Case Study with a Low-Concentration Therapeutic Protein Product in a Prefilled Syringe.Pharmaceutical research · 2016Article
- Antibody-Drug Conjugates: Design, Formulation and Physicochemical Stability.Pharmaceutical research · 2015Review
- Article
- Redox potential ultrasensitive nanoparticle for the targeted delivery of camptothecin to HER2-positive cancer cells.Molecular pharmaceutics · 2014Article
- Quality control and stability studies with the monoclonal antibody, trastuzumab: application of 1D- vs. 2D-gel electrophoresis.International journal of molecular sciences · 2014Article
- Quantitation of pH-induced aggregation in binary protein mixtures by dielectric spectroscopy.The protein journal · 2012Article
- Structure and function of purified monoclonal antibody dimers induced by different stress conditions.Pharmaceutical research · 2012Article
- Protein particulate detection issues in biotherapeutics development--current status.AAPS PharmSciTech · 2012Review
- Article
- Article
- Article
- Article
- Article
- Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aggregation compromises the safety and efficacy of therapeutic proteins. According to the manufacturer, the therapeutic immunoglobulin trastuzumab (Herceptin) should be diluted in 0.9% sodium chloride before administration. Dilution in 5% dextrose solutions is prohibited. The reason for the interdiction is not mentioned in the Food and Drug Administration (FDA) documentation, but the European Medicines Agency (EMEA) Summary of Product Characteristics states that dilution of trastuzumab in dextrose solutions results in protein aggregation. In this paper, asymmetrical flow field-flow fractionation (FFF), fluorescence spectroscopy, fluorescence microscopy and transmission electron microscopy (TEM) have been used to characterize trastuzumab samples diluted in 0.9% sodium chloride, a stable infusion solution, as well as in 5% dextrose (a solution prone to aggregation). When trastuzumab samples were injected in the FFF channel using a standard separation method, no difference could be seen between trastuzumab diluted in sodium chloride and trastuzumab diluted in dextrose. However, during FFF measurements made with appropriate protocols, aggregates were detected in 5% dextrose. The parameters enabling the detection of reversible trastuzumab aggregates are described. Aggregates could also be documented by fluorescence microscopy and TEM. Fluorescence spectroscopy data were indicative of conformational changes consistent with increased aggregation and adsorption to surfaces. The analytical methods presented in this study were able to detect and characterize trastuzumab aggregates.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.