High-Resolution Characterization of ADCs by Orbitrap LCMS

Area of Science:

• Biochemistry
• Analytical Chemistry
• Pharmacology

Background:

• Antibody-drug conjugates (ADCs) possess complex structures, integrating small and large molecules.
• ADCs are susceptible to biotransformation in vivo, necessitating robust analytical methods for stability assessment.

Purpose of the Study:

• To introduce a high-resolution Orbitrap mass spectrometry (MS) approach for characterizing ADC biotransformation.
• To demonstrate the advantages of this method over conventional techniques for ADC catabolite analysis.

Main Methods:

• Utilized a high-resolution Orbitrap MS platform for ADC analysis.
• Compared the performance of Orbitrap MS with a conventional quadrupole time-of-flight (Q-TOF) MS approach.

Main Results:

• The Orbitrap MS method significantly improved mass resolution compared to Q-TOF MS.
• Achieved more comprehensive characterization of ADC catabolites, especially those with minor mass alterations.
• Enabled detailed insights into ADC biotransformation pathways and stability.

Conclusions:

• High-resolution Orbitrap MS is a powerful tool for detailed ADC biotransformation and stability studies.
• This method offers enhanced capabilities for identifying subtle changes in ADC structures over time.
• The approach is particularly valuable for quality control and pharmacokinetic studies of ADCs.