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Metabolism investigation of New drugs from in vitro biotransformation by LC-MS/MS

Grant number: 11/23413-3
Support Opportunities:Scholarships in Brazil - Post-Doctorate
Effective date (Start): July 01, 2012
Effective date (End): November 30, 2012
Field of knowledge:Physical Sciences and Mathematics - Chemistry - Analytical Chemistry
Principal Investigator:Regina Vincenzi Oliveira
Grantee:Bianca Ferreira da Silva
Host Institution: Centro de Ciências Exatas e de Tecnologia (CCET). Universidade Federal de São Carlos (UFSCAR). São Carlos , SP, Brazil


The main factors that prevent the introduction of new drugs on the market have a direct or correlation with pharmacokinetic problems.The knowledge of the biotransformation products (metabolites) formed during the metabolism of a bioactive compound is of fundamental importance in the development of new drugs, to characterize the pharmacokinetics of the chemical compound. Therefore, this project proposes to conduct studies of biotransformation of pro drugs with high potential through in vitro incubation of compounds with microsomal fractions obtained from livers of Wister rats and also with human microsomal fractions, with subsequent identification/structural characterization of the major metabolites formed, as well as with studies of phenotyping to identify the isoforms of CYP 450 system involved in the metabolic process.The demand for analysis of samples and/or complex matrices, efficiency and reduced analysis time, has driven the use of hyphenated analytical techniques such as liquid chromatography coupled with mass spectrometry (LC-MS/MS) and liquid chromatography with nuclear magnetic resonance (LC-NMR).Thus, for the development of the project it will be used optimized analytical methods involving the use of LC-MS/MS and LC-NMR, since these techniques have been applied to the analysis, identification and characterization of molecules, such as metabolites, in order to save time and avoid isolation and studies of low activity of compound interest.

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
CARDOSO, JOSIANE DE O.; DA SILVA, BIANCA F.; VENANCIO, TIAGO; DA ROCHA PITTA, MARINA G.; PITTA, IVAN DA R.; PECCININI, ROSANGELA G.; OLIVEIRA, REGINA V.. Study of the in vitro metabolic profile of a new alpha(2)-adrenergic agonist Cheek for in rat and human liver microsomes by using liquid chromatography-multiple-stage mass spectrometry and nuclear magnetic resonance. Journal of Pharmaceutical and Biomedical Analysis, v. 172, p. 67-77, . (11/23413-3)

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