Site-Specific Conjugation Quantitation of a Cysteine-Conjugated Antibody-Drug Conjugate Using Stable Isotope Labeling Peptide Mapping LC-MS/MS Analysis.
Anal Chem
; 94(6): 2772-2778, 2022 02 15.
Article
en En
| MEDLINE
| ID: mdl-35100801
ABSTRACT
Drug-load (DL) characterization of antibody-drug conjugates (ADCs) is an important analytical task due to its designation as a critical quality attribute (CQA) affecting potency and stability. Intact and subunit liquid chromatography-mass spectrometry (LC-MS) analyses can determine global drug-to-antibody ratios (DARs) that correlate well with other orthogonal analytical methods; however, peptide mapping liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis has struggled to provide complementary site-specific quantitation of drug conjugation sites. The peptide mapping method described herein utilizes stable isotope labeling to accurately quantitate the site-specific conjugation levels of a cysteine-conjugated ADC to provide "bottom-up" DAR characterization in parallel with protein sequence and post-translational modification (PTM) characterization in one multi-attribute analytical method (MAM).
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1
Base de datos:
MEDLINE
Asunto principal:
Inmunoconjugados
Idioma:
En
Revista:
Anal Chem
Año:
2022
Tipo del documento:
Article
País de afiliación:
Estados Unidos