Of drug metabolites

An automatic solid phase extraction system was developed by Scott and Kucera (3) for the determination of drug metabolites in blood. The system was basically a multi-column switching system utilizing... 

The Use of Target-Compound Analysis and LC-MS-MS for the Identification of Drug Metabolites... 

The Use of High-Accuracy Mass Measurements in Combination with LC-MS for the Structure Determination of Drug Metabolites... 

Figure 5.45 Structures of (1) Bosentan (C27H29N5O6S [M + H]+ 552.1917) and three of its metabolites, formed by (2) oxidation (C27H29N5O7S [M + H]+ 568.1866), (3) demethylation (C26H27N5O6S [M- -H]+ 538.1760), and (4) demethylation-oxidation (C26H27N5O7S [M + M]+ 554.1709). Reprinted by permission of Elsevier Science from Exact mass measurement of product ions for the structural elucidation of drug metabolites with a tandem quadrupole orthogonal-acceleration time-of-flight mass spectrometer , by Hopfgartner, G., Chemushevich, I. V., Covey, T., Plomley, 1. B. and Bonner, R., Journal of the American Society for Mass Spectrometry, Vol. 10, pp. 1305-1314, Copyright 1999 by the American Society for Mass Spectrometry.

Chapters 9 and 10 focus on synthesis of drug metabolites and intermediates catalyzed by P450s or whole cells. 

Recent US FDA guidance on safety testing of drug metabolites [5] highlights the importance of measuring major metabolites in human and toxicological species. This increased scrutiny on the role of metabolites in the evaluation of efficacy and safety will lead to increasing demand for metabolites as analytical standards. 

US Food Drug Adminstration (2008) Guidance for Industry, Safety Testing of Drug Metabolites, http //www.fda. gov/cder/guidance/index.htm (last access October 2008). 

Vail, R.B., Homann, M.J., Hanna, I. and Zaks, A. (2005) Preparative synthesis of drug metabolites using human cytochrome P450s 3A4, 2C9 and 1A2 with NADPH P450 reductase expressed in Escherichia coli. Journal of Industrial Microbiology Biotechnology, 32, 67-74. 

Osorio-Lozada, A., Surapaneni, S., Skiles, G. and Subramanian, R. (2008) Biosynthesis of drug metabolites using microbes in hollow fiber cartridge reactors case study of diclofenac metabolism by Actinoplanes sp. Drug Metabolism and Disposition The Biological Fate of Chemicals, 36, 234-240. 

Chowdhury, S.E., Ed. Progress in Pharmaceutical and Biomedical Analysis Volume 6 Identification and Quantification of Drugs, Metabolites and Metabolizing Enzymes by LC-MS, 2005, New York Elsevier. 

Studies of Drug Metabolites. Major active metabolite(s) should be identified and deserve detailed pharacokinetic study. Timing of the metabolic assessment studies within the development plan depends on the characteristics of the individual drug. 

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