Microscale Purification with Direct Charged Aerosol Detector Quantitation Using Selective Online One- or
Kanaka Hettiarachchi1, Eric Streckfuss2, Jillian R Sanzone3
1Discovery Chemistry, Merck & Co., Inc., 213. E. Grand Avenue, South San Francisco, California 94080, United States.
Analytical Chemistry
|June 3, 2022
Summary
This study introduces an online microscale liquid chromatography (LC) system for rapid purification and analysis of pharmaceutical compounds. The platform offers significant time and cost savings for microscale quantitation without gravimetric methods.
Area of Science:
- Analytical Chemistry
- Pharmaceutical Science
- Chromatography
Background:
- Pharmaceutical industry faces challenges in microscale separation of complex mixtures.
- Need for rapid isolation, impurity determination, and quantitation of target compounds.
Purpose of the Study:
- To describe an online microscale one- or two-dimensional liquid chromatography (1D/2D-LC) system.
- To highlight the advantages of charged aerosol detection (CAD) for microscale quantitation.
Main Methods:
- Online microscale 1D/2D-LC system with heart-cutting and multi-detector triggering.
- Utilized charged aerosol detection (CAD) for direct quantitation.
- Purified 0.5-5.0 mg scale reactions in 96- or 384-well plates.
Main Results:
- Achieved separations in less than 12 minutes, including trapping and equilibration.
- Demonstrated direct quantitation of limited samples using CAD without extra instruments.
- Enabled purification of investigational compounds at high purity.
Conclusions:
- The developed platform offers significant time and cost savings for microscale analysis.
- Facilitates rapid exploration of chemical reaction parameters and synthetic route scouting.
- Supports efficient biological target validation through rapid compound isolation.
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