Liquid chromatography/mass drug discovery applications

Xu, X. Zhou, Q. Korfmacher, W. A. Development of a low volume plasma sample precipitation procedure for liquid chromatography/tandem mass spectrometry assays used for drug discovery applications. Rapid Commun Mass Spectrom 2005, 19, 2131-2136. 

Cai, Z., Han, C., Harrelson, S., Fung, E., and Sinhababu, A. K. (2001). High-throughput analysis in drug discovery Application of liquid chromatography/ion-trap mass spectrometry for simultaneous cassette analysis of alpha-la antagonists and their metabolites in mouse plasma. Rapid Commun. Mass Spectrom. 15 546-550. 

Mei H, Hseih Y, Nardo C, Xu X, Wang S, et al. 2003. Investigation of matrix effects in bioanalytical high performance liquid chromatography/tandem, mass spectrometrometic assay application to drug discovery. Rapid Commun Mass Spectrom 17 97-103. 

Mei, H. Hsieh, Y Nardo, C. Xu, X. Wang, S. Ng, K. Korfmacher, W.A. Investigation of Matrix Effects in Bioanalytical High-Performance Liquid Chromatography/Tandem Mass Spectrometric Assays Application to Drug Discovery, Rapid Commun. Mass Spectrom. 17, 97-103 (2003). 

Liquid chromatography is an essential analytical tool for the separation of proteins in biotechnology and pharmaceutical product development. Applications are found throughout the development process of biological products, from drug discovery to quality control. Molecular properties of proteins, like molecular mass, net charge, hydrophobicity, and structure give ample opportunities to use HPLC for their separation. 

In conclusion, NMR is an essential tool for the successful determination of crucial metabolite structures and is routinely used in the pharmaceutical industry. As discussed, metabolite structure problems could be as simple as hydroxylation on an aromatic ring or as complex as a rearrangement depicted in the formation of glutathione adducts. NMR provides a vast and continually expanding combination of techniques applicable to the analysis of metabolite structures. The judicious choice of NMR experiments based on the particulars of the system and the nature of the metabolites can be combined with mass spectrometry and liquid chromatography to successfully analyze a variety of biological metabolites to benefit drug discovery. 

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