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Updated: Jul 11, 2026
10:17
High-throughput and Comprehensive Drug Surveillance Using Multisegment Injection-Capillary Electrophoresis-Mass Spectrometry
Published on: April 23, 2019
A generic fast solid-phase extraction high-performance liquid chromatography/mass spectrometry method for
Lan Gao1, Xueheng Cheng, Jun Zhang
1Department of Biological Screening, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL, USA. lan.gao2007@yahoo.com
Rapid Communications in Mass Spectrometry : RCM
|October 9, 2007
Summary
A new generic fast method using online solid-phase extraction coupled with high-performance liquid chromatography/mass spectrometry (SPE-HPLC/MS) enables rapid drug screening. This method efficiently analyzes diverse compounds for drug discovery, achieving high throughput and reliable results.
Area of Science:
- Analytical Chemistry
- Pharmacology
- Biochemistry
Background:
- High-performance liquid chromatography/mass spectrometry (HPLC/MS) is crucial for drug discovery, including screening, lead identification, and ADME profiling.
- High-throughput screening requires a versatile LC/MS method capable of analyzing a wide range of compounds efficiently.
- Existing methods often lack the generic applicability needed for diverse compound libraries in early-stage drug development.
Purpose of the Study:
- To develop a generic, fast, and robust LC/MS method for high-throughput drug screening.
- To optimize a column-switching mechanism for on-line solid-phase extraction (SPE)-HPLC/MS analysis.
- To validate the method's performance across diverse chemical properties and large compound sets.
Main Methods:
- Development of a generic fast SPE-HPLC/MS method utilizing a column-switching mechanism.
- Method optimization guided by a small set of compounds with varied properties.
- Analysis of 658 diverse small molecules to assess method performance and throughput.
Main Results:
- Achieved a sample throughput of 1.7 minutes per sample with good peak separation and shape.
- Demonstrated a linear response range from 1 to 500 nM for tested compounds.
- Successfully analyzed 612 out of 658 randomly selected small molecules with good signal intensity and peak shape.
Conclusions:
- The developed generic fast SPE-LC/MS method is suitable for high-throughput drug screening and analysis.
- The method has been successfully applied to screen over 1.5 million compounds and quantify binding constants for over 7000 compounds.
- This approach significantly enhances efficiency in drug discovery by enabling rapid assessment of compound properties and target interactions.
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