A simple and highly sensitive LC-MS workflow for characterization and quantification of ADC cleavable payloads.
Sci Rep
; 14(1): 11018, 2024 05 14.
Article
en En
| MEDLINE
| ID: mdl-38744902
ABSTRACT
Antibody-drug conjugates (ADC) payloads are cleavable drugs that act as the warhead to exert an ADC's cytotoxic effects on cancer cells intracellularly. A simple and highly sensitive workflow is developed and validated for the simultaneous quantification of six ADC payloads, namely SN-38, MTX, DXd, MMAE, MMAF and Calicheamicin (CM). The workflow consists of a short and simple sample extraction using a methanol-ethanol mixture, followed by a fast liquid chromatography tandem mass spectrometry (LC-MS/MS) analysis. The results showed that well-validated linear response ranges of 0.4-100 nM for SN38, MTX and DXd, 0.04-100 nM for MMAE and MMAF, 0.4-1000 nM for CM were achieved in mouse serum. Recoveries for all six payloads at three different concentrations (low, medium and high) were more than 85%. An ultra-low sample volume of only 5 µL of serum is required due to the high sensitivity of the method. This validated method was successfully applied to a pharmacokinetic study to quantify MMAE in mouse serum samples.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Inmunoconjugados
/
Espectrometría de Masas en Tándem
Límite:
Animals
Idioma:
En
Revista:
Sci Rep
Año:
2024
Tipo del documento:
Article
País de afiliación:
Singapur