Compound-library creation, analysis, profiling, and management are integral components of modern drug-discovery efforts. With well-validated targets and assays, the success of drug lead discovery and optimization has largely depended upon the diversity and quality of the compound library. As an analytical technique, mass spectrometry has played an important role in these drug-discovery activities. The widespread application of mass spectrometry for chemical-library analysis is due to the unique features such as high speed, sensitivity, selectivity, general applicability to diverse compounds, as well as the ease of coupling of modern ionization techniques with liquid handling and separation techniques. Thus, mass spectrometry-based methods have become an important enabling technology for compound-library analysis, purification, and profiling. Parallel processing, open access, and automation (i.e., analysis, data processing, interpretation, and reporting of results) have been the major trends in recent years. Continued development of mass spectrometry-based techniques in the analysis of compound libraries is likely in the foreseeable future.
Improvement in LC-MS and LC-MS/MS analysis throughput has been reported by the use of monolithic silica columns to increase the speed of chromatography separation [156-158]. The substitution of an SFC front end to MS in lieu of HPLC has been a growing trend in compound library analysis. It is possible that the use of SFC-MS will be extended to in vitro and in vivo evaluation of library compounds such as ADME and DMPK. CE-MS has not been widely used in the analysis of combinatorial libraries. To date, the application of CE-MS has been frequently in the analysis of mixture-component libraries derived from split synthesis and in the affinity screening of libraries through ACE. However, with the miniaturization of biological screening in the "lab-on-a-chip" format, CE-MS may find renewed interest due to the ease of coupling CE with miniaturized biochip separation platforms [159-162]. Thus, miniaturization and chip-based technology may be an important new development for the analysis of compound libraries in conjunction with the biological testing of these compounds. Several new developments addressed chip-based analysis with different strategies. Researchers from Advion Biosceinces developed the NanoMate device for chip-based nano-ESI mass spectrometry analysis. Applications in proteomics and pharmacokinetcs have been reported . An alternative nano-ESI device with polymer chips has been reported with Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR-MS) . In addition, a chip-based parallel LC device has been developed. Researchers from Nanostream have reported a 24-channel parallel HPLC chip device with UV detection . The device will need to be coupled with mass spectrometry detection to make full use of the power of the microscale separation and analysis. Trends in library purification seem to be directed more toward mass-triggered collection technologies in place of UV-, ELSD-, or CLND-triggered collection. Further, SFC has seen a growth in acceptance for the preparative purification of combinatorial libraries. The format has already been formatted to provide a MS-triggered format. In compound-library management, the routine quality control of compounds will be facilitated by development of high throughput LC-MS technique in combination with good quantitation modules such as UV, ELSD, or CLND. It is also possible that these will be implemented in a parallel separation format with miniaturized chip devices .
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