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Accelerating Pharmaceutical Process Development with an Acoustic Droplet Ejection-Multiple Reaction Monitoring-Mass

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Acoustic droplet ejection-multiple reaction monitoring-mass spectrometry (ADE-MRM-MS) accelerates pharmaceutical research by enabling rapid, sensitive, and selective nanoliter-scale measurements. This high-throughput workflow enhances reaction screening and catalyst development.

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Area of Science:

  • Analytical Chemistry
  • Chemical Engineering
  • Biotechnology

Background:

  • Pharmaceutical process development demands faster, more sensitive analytical assays for small sample volumes.
  • Acoustic droplet ejection (ADE) coupled with mass spectrometry offers high-throughput nanoliter measurements directly from microplates.

Purpose of the Study:

  • To introduce and validate an Acoustic Droplet Ejection-Multiple Reaction Monitoring-Mass Spectrometry (ADE-MRM-MS) workflow.
  • To accelerate pharmaceutical process research and development (PR&D) through enhanced analytical capabilities.

Main Methods:

  • Developed a systematic ADE-MRM-MS workflow for data-driven selection of MRM transitions and assay optimization.
  • Utilized rapid measurements (1 sample/s) for efficient parameter tuning.
  • Applied the workflow to screen Ni-based catalysts and enzyme libraries for specific reactions.

Main Results:

  • Achieved analytical assays with excellent sensitivity, selectivity, and speed for PR&D reaction screenings.
  • Successfully guided industrial processes including catalyst screening (1 Hz) and enzyme library screening.
  • Demonstrated ADE-MRM-MS assays provide accurate results comparable to conventional LC, with over 100-fold throughput increase.

Conclusions:

  • The ADE-MRM-MS workflow significantly enhances the speed and efficiency of pharmaceutical R&D.
  • This method enables high-throughput screening and optimization of chemical reactions and biological catalysts.
  • ADE-MRM-MS represents a powerful analytical tool for modern drug discovery and process development.