Combinatorial chemistry Quality control

Lead optimization Combinatorial/medicinal chemistry support Open access Purification Combinatorial mixtures Combinatorial libraries-quality control Taylor et al., 1995 Pullen et al., 1995 Zeng and Kassel, 1998 Zeng et al., 1998 Richmond et al., 1999 Yates et al., 2001 Dunayevskiy et al., 1995 Fang et al., 1998 Fitch 1998-1999 FIsu et al., 1999 Dulery et al., 1999 Ventura et al., 2000 Shah et al., 2000... 

Today an increasing importance of qualitative analysis can be stated in certain fields. This is due to an increasing number of materials under study, especially active agents of interest on the one hand, and the many and diverse ways of synthesis (e.g., by combinatorial chemistry) on the other hand as well as the increasing demands on quality. Because analytical laboratories in research and routine control would be overtaxed in their capacity if full quantitative analyses were done generally, screening methods become more and more significant. 

Mass spectrometry is an indispensable analytical tool in chemistry, biochemistry, pharmacy, and medicine. No student, researcher or practitioner in these disciplines can really get along without a substantial knowledge of mass spectrometry. Mass spectrometry is employed to analyze combinatorial libraries [1,2] sequence biomolecules, [3] and help explore single cells [4,5] or other planets. [6] Structure elucidation of unknowns, environmental and forensic analytics, quality control of drugs, flavors and polymers they all rely to a great extent on mass spectrometry. [7-11]... 

However, this assertion is based on the assumption that the compounds intended to be made were actually made in sufficient quantities and to adequate levels of purity. The yields in many Combinatorial Chemistry synthesis vary significantly and the purity may also be problematic. The additional steps required to purify and measure the quantity generated are not usually necessary to establish whether the major product shows any significant biological activity. It is therefore not surprising that many companies perform quality control checks on a subset oftheir samples. This prohibits accurate decisions on the overlap of libraries. 

E. Letot, G. Koch, R. Falchetto, G. Bovermann, L. Oberer and H.-J. Roth, Quality control in combinatorial chemistry determinations of amounts and comparison of the purity of LC-MS-purified samples by NMR, LC-UV and CLND, J. Comb. Chem., 2005, 7(3), 364. 

In addition to quality control over compound collections, the issue of purity of synthetic libraries derived using combinatorial chemistry quickly came under the microscope. In the early to mid-1990s, combichem became a household word throughout the pharmaceutical industry and was believed to be a key technology that would revolutionize drug discovery. The basis of... 

The use of mass spectrometric identification in combinatorial chemistry is not limited to the analysis of synthetic products as a means of quality control, but also for the identifica-... 

A very important use of MS in combinatorial chemistry is in quality control of combinatorial libraries. As much as possible, we would like to have pure compounds generated in high yield, with no side reactions or by-products. We also need to verify that every component actually exists in a library (i.c.. that no reactions failed). Only MS provides the sensitivity and versatility to perform this checking with both solid-pha.se and solution-phase libraries... 

For a recent review of analytical methods used for the quality control of combinatorial libraries, see WL Fitch. Analytical methods for the quality control of combinatorial libraries. In W Moos, M Pavia, B Kay, A Ellington, eds. Annual Reports in Combinatorial Chemistry and Molecular Diversity, Vol. 1. Leiden, The Netherlands ESCOM, 1997, pp 59-68. 

Yan B, Fang L, Irving M, Zhang S, Boldi AM, Woolard F, Johnson CR, Kshirsagar T, Figliozzi CM, Krueger CA, and Collins N. Quality Control in Combinatorial Chemistry Determination of the Quantity, Purity, and Quantitative Purity of Compounds in Combinatorial Libraries. / Com Chem 2003 5 547-559. 

Yan, B. et al. Quality control in combinatorial chemistry Determination of the quantity, purity, and quantitative purity of compounds in combinatorial libraries. J. Comb. Chem. 2003, 5, 547-559. 

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