Details

Autor(en) / Beteiligte

• Mak, Shi Ya
• Chen, Shuwen
• Fong, Wey Jia
• Choo, Andre
• Ho, Ying Swan

Titel

A simple and highly sensitive LC-MS workflow for characterization and quantification of ADC cleavable payloads

Ist Teil von

• Scientific reports, 2024-05, Vol.14 (1), p.11018-11018

Ort / Verlag

England: Nature Publishing Group

Erscheinungsjahr

2024

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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.