Provider: Ingenta Connect Database: Ingenta Connect Content: application/x-research-info-systems TY - ABST AU - Iglesias, Jacobo AU - Sleno, Lekha AU - A. Volmer, Dietrich TI - Isotopic Labeling of Metabolites in Drug Discovery Applications JO - Current Drug Metabolism PY - 2012-11-01T00:00:00/// VL - 13 IS - 9 SP - 1213 EP - 1225 KW - biomarker KW - mass spectrometry KW - stable isotope labeling KW - ADMET KW - drug metabolites KW - differential quantitation KW - metabolomics N2 - Understanding the metabolic and pharmacokinetic fate of a drug in humans is a key factor in its development and registration, as well as in the elaboration of new therapeutic agents. To carry out these studies, stable isotope labeling techniques have been effectively used by drug metabolism scientists and toxicologists in order to gain better understanding of the drugs’ disposition, bioavailability and toxicity in in vivo studies. Among the different analytical techniques used, mass spectrometry (MS) coupled to separation techniques has become the detection method of choice due to its high sensitivity and selectivity. In vitro quantification of metabolite levels in biofluids by MS is often difficult if a proper internal standard is not available due to the inherent problems associated with the technique (e.g. chromatographic coelutions, ion suppression, low reproducibility etc.). Stable isotope coding approaches alleviate these drawbacks and allow comparative drug metabolomics studies similarly to the differential proteomic techniques developed in the last decade. This review describes a selection of methodological improvements in the use of stable isotopes labeling in combination with MS to detect drug metabolites. In the first part of the paper, the application of labeled compounds to study the absorption, distribution, metabolism, excretion and toxicology of drugs (ADMET) in addition to the elucidation of metabolic pathways is presented. In the second part, recent developments of stable isotope coded tags for the in vitro relative metabolite quantification in biofluids are presented. UR - https://www.ingentaconnect.com/content/ben/cdm/2012/00000013/00000009/art00003 M3 - doi:10.2174/138920012803341357 UR - https://doi.org/10.2174/138920012803341357 ER -