Determination of drug-to-antibody ratio of antibody-drug conjugate in biological samples using microflow-liquid chromatography/high-resolution mass spectrometry.
Bioanalysis
; 14(24): 1533-1545, 2022 Dec.
Article
en En
| MEDLINE
| ID: mdl-36825963
Drug-to-antibody ratio (DAR), payload release and metabolite profile of deconjugated payload-linker of vorsetuzumab maleimidocaproyl valine-citrulline p-aminobenzyloxycarbonyl monomethyl auristatin E, an antibodydrug conjugate (ADC) with cleavable linker and monomethyl auristatin E as payload, are reported. Species-specific retention of DAR, payload release and metabolite patterns of deconjugated payload-linker of the ADC are summarized. Exploring the fate of payload-linker moieties deconjugated from ADCs in the body is also vital to understanding pharmacological activity and toxicity. Species-specific metabolite patterns of the ADC provided insight into the importance of optimization of the payload-linker moiety in biological samples, especially in humans. In terms of a more sensitive analytical platform for drug metabolism and pharmacokinetic evaluation, microflow-liquid chromatography/high-resolution mass spectrometry (LCHRMS) in DAR analysis was found to take advantage of the improvement of detection sensitivity compared with conventional LCHRMS. Because ADCs are a complex drug modality, these results indicated the importance of evaluation of ADCs from a drug metabolism and pharmacokinetics point of view to understand the pharmacology and toxicology of ADCs, more precisely.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Inmunoconjugados
/
Antineoplásicos
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Bioanalysis
Año:
2022
Tipo del documento:
Article
País de afiliación:
Japón