Calculated conjugated payload from immunoassay and LC-MS intact protein analysis measurements of antibody-drug conjugate.
Bioanalysis
; 8(21): 2205-2217, 2016 Nov.
Article
en En
| MEDLINE
| ID: mdl-27682846
ABSTRACT
AIM:
Complex nature of bioconjugates require multiple bioanalytical approaches to support PK and absorption, distribution, metabolism and excretion characterization. For antibody-drug conjugate (ADC) bioanalysis both LC-MS and ligand-binding assays (LBAs) are employed.RESULTS:
A method consisting of immunocapture extraction of ADC from biomatrices followed by LC-MS analysis of light and heavy chain is described. Drug antibody ratio (DAR) profiles of ADC Tras-mcVC-PF06380101 dosed at 0.3, 1 and 3 mg/kg in Sprague Dawley rats were obtained. Combined with total antibody (monoclonal antibody) measurement by LBA, conjugated payload concentration was calculated.CONCLUSION:
PK profiles from LBA, ADC and calculated conjugated payload (DAR × monoclonal antibody) were in good agreement. We present a new tool for PK assessment of ADCs while also exploring ADC metabolism and DAR sensitivity of LBA ADC assay.Palabras clave
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Espectrometría de Masas
/
Preparaciones Farmacéuticas
/
Inmunoconjugados
/
Anticuerpos Monoclonales
Límite:
Animals
Idioma:
En
Revista:
Bioanalysis
Año:
2016
Tipo del documento:
Article
País de afiliación:
Estados Unidos