A centralized approach to tandem mass spectrometry method development for high-throughput ADME screening

Area of Science:

• Analytical Chemistry
• Bioanalytical Mass Spectrometry
• Drug Discovery

Background:

• Efficient acquisition and dissemination of tandem mass spectrometry (MS/MS) conditions are crucial for ADME-screening bioanalytical groups.
• Current methods may lack standardization and automation, leading to variability and reduced throughput.

Purpose of the Study:

• To develop and implement a centralized system for acquiring and disseminating MS/MS conditions for ADME screening.
• To evaluate the impact of automated optimization of declustering potential (DP) and collision energy (CE) on assay sensitivity and efficiency.

Main Methods:

• Utilized two automated software products, Autoscan and Automaton, for MDS Sciex mass spectrometers.
• Autoscan determined optimal polarity and collision energy (CE); Automaton determined optimal declustering potential (DP) and CE.
• Optimized MS/MS conditions were stored in a central database for LC/MS/MS bioanalysis workstations.

Main Results:

• Automated optimization significantly improved signal response, with an average increase of 27% for DP optimization.
• DP optimization yielded signal enhancements greater than 50% for approximately 10% of compounds.
• Testing three CE values (1, 30, and 45 V) provided adequate coverage for most small molecule drug discovery analytes.

Conclusions:

• A centralized, automated approach to MS/MS condition optimization enhances ADME screening efficiency and sensitivity.
• Generic DP settings (e.g., 25 V) are suitable for most ADME screening, while CE optimization requires testing multiple values.
• The developed system facilitates rapid method development and improves data reliability in bioanalytical mass spectrometry.