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Quality assessment of combinatorial pooled libraries using mass spectrometry
P H Lambert1, S Bertin, J L Fauchère
1Institut de Recherches SERVIER, Division de Physico-Chimie Analytique, 11, rue des Moulineaux, 92150 Suresnes, France. pierre-herve.lambert@fr.netgrs.com
Combinatorial Chemistry & High Throughput Screening
|July 27, 2001
Summary
Combinatorial chemistry generates compound libraries that require advanced analytical methods for identification. Mass spectrometry, particularly tandem mass spectrometry, is crucial for analyzing these complex mixtures and identifying active compounds.
Area of Science:
- Analytical Chemistry
- Organic Chemistry
- Mass Spectrometry
Background:
- Combinatorial chemistry produces compound libraries as mixtures, necessitating deconvolution for hit identification.
- Parallel synthesis yields single compounds identifiable by location, contrasting with mixture-based combinatorial approaches.
- Analytical methods, especially mass spectrometry, are vital for the success of combinatorial chemistry strategies.
Purpose of the Study:
- To discuss the role and application of mass spectrometry in analyzing combinatorial chemistry libraries.
- To explore various mass spectrometric techniques for identifying library components and by-products.
- To evaluate methods for quantitative analysis and equimolarity assessment of compound libraries.
Main Methods:
- Utilizing various mass spectrometric techniques, including tandem mass spectrometry (MS/MS).
- Employing separation techniques like liquid chromatography-mass spectrometry (LC-MS) and high-resolution mass spectrometry.
- Exploring precursor ion scans, product ion scans, and constant neutral loss scans for library characterization.
- Suggesting evaporative light scattering detector (ELSD) and chemiluminescent nitrogen detector (CLND) for quantitative analysis.
Main Results:
- Mass spectrometry is essential for identifying components in combinatorial libraries, including by-products.
- Tandem mass spectrometry can exploit common fragmentation patterns to detect specific product subfamilies.
- LC-MS and high-resolution mass spectrometry aid in separating library members based on mass and elution time.
- ELSD and CLND are proposed as suitable detectors for quantitative analysis of library equimolarity.
Conclusions:
- Mass spectrometry is indispensable for the analysis and characterization of combinatorial chemistry libraries.
- Tandem mass spectrometry offers specific detection capabilities for library subfamilies.
- Effective quantitative analysis of libraries requires specialized detectors like ELSD or CLND.