MALDI-MS: a Rapid and Reliable Method for Drug-to-Antibody Ratio Determination of Antibody-Drug Conjugates
Antibodies, Monoclonal
/ analysis
Antineoplastic Agents
/ analysis
Immunoconjugates
/ analysis
Molecular Weight
Peptides
/ analysis
Reproducibility of Results
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
/ methods
Spectrophotometry, Ultraviolet
Trastuzumab
/ analysis
Trypsin
/ metabolism
Antibody-drug conjugate
Mass spectrometry
Trastuzumab
Journal
Iranian biomedical journal
ISSN: 2008-823X
Titre abrégé: Iran Biomed J
Pays: Iran
ID NLM: 9814853
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
entrez:
21
5
2019
pubmed:
21
5
2019
medline:
18
2
2020
Statut:
ppublish
Résumé
It is believed that the loading value of anticancer drug conjugated to the monoclonal antibody, called drug-to-antibody ratio (DAR), is the main quality feature of antibody-drug conjugates. In this study, matrix assisted laser desorption/ionization mass spectrometry was used to determine the average molecular weight of trastuzumab and its three conjugated forms. The differences in the measured masses for each conjugate and unconjugated trastuzumab were compared to the expected mass change through the conjugation of one mole of related drug-linker, in order to measure DAR. There was a consistency between the loading results of mass spectrometry and the measurements of UV spectrometry in most cases. According to our findings, the MALDI-MS method for determining the loading values can be used rapidly and reliably to estimate the covalently bound drugs conjugated to antibodies when ESI-TOF-MS is unavailable.
Sections du résumé
Background
It is believed that the loading value of anticancer drug conjugated to the monoclonal antibody, called drug-to-antibody ratio (DAR), is the main quality feature of antibody-drug conjugates.
Methods
In this study, matrix assisted laser desorption/ionization mass spectrometry was used to determine the average molecular weight of trastuzumab and its three conjugated forms. The differences in the measured masses for each conjugate and unconjugated trastuzumab were compared to the expected mass change through the conjugation of one mole of related drug-linker, in order to measure DAR.
Results
There was a consistency between the loading results of mass spectrometry and the measurements of UV spectrometry in most cases.
Conclusion
According to our findings, the MALDI-MS method for determining the loading values can be used rapidly and reliably to estimate the covalently bound drugs conjugated to antibodies when ESI-TOF-MS is unavailable.
Substances chimiques
Antibodies, Monoclonal
0
Antineoplastic Agents
0
Immunoconjugates
0
Peptides
0
Trypsin
EC 3.4.21.4
Trastuzumab
P188ANX8CK
Types de publication
Journal Article
Langues
eng
Pagination
395-403Références
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