11

APPLICATION OF LIQUID

CHROMATOGRAPHY/MASS

SPECTROMETRY FOR METABOLITE

IDENTIFICATION

SHUGUANGMA ANDSWAPANK. CHOWDHURY

11.1 INTRODUCTION

Metabolites are chemical entities formed as a result of biotransformation of
endogenous compounds and xenobiotics. In general, metabolism leads to more
hydrophilic species compared to the progenitor molecules thus facilitating the
elimination from the body. Metabolic pathways are classified as nonsynthetic
or Phase I (e.g., oxidation, reduction, and hydrolysis) and synthetic or Phase II
(e.g., conjugation) reactions. The assessment of the metabolic fate of the drug
candidates, knowledge of the routes and extent of metabolism in animals and
humans, and evaluation of the biological properties of metabolites, represent
important objectives in pharmaceutical research. Metabolites could be
pharmacologically active, toxic, or involved in drug–drug interactions;
therefore, metabolite identification plays a pivotal role in various phases of
drug discovery and development. Identification of pharmacologically active
metabolites leads to protection of intellectual properties as these metabolites
can potentially become next generation drugs.
Metabolite characterization is complicated by the fact that metabolism often
produces a multitude of relatively low concentration (nM tomM) structurally
diverse compounds. In addition, biological matrices containing a large excess of

Drug Metabolism in Drug Design and Development, Edited by Donglu Zhang, Mingshe Zhu
and W. Griffith Humphreys
Copyright#2008 John Wiley & Sons, Inc.

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