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ANANBIOANAL - 2010
Pharmaceutical R & D Summit
Application of Current Approaches and Newer Trends in
Identification of Drug Metabolites Using Liquid Chromatography-
Mass Spectrometry
Bhagwat Prasad and Saranjit Singh
Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), Punjab, India
M
etabolite identification is amongst the important studies during early stages
of drug development because metabolic products may be pharmacologically
active or toxic in nature. In the last one decade, there have been revolutionary
changes in the way metabolite identification is carried out. This has mainly become
possible due to the advent of sophisticated analytical modalities, particularly,
hyphenated liquid chromatography-mass spectrometry (LC-MS). There are varieties
of LC-MS systems available with difference in their utility in metabolite identification.
Particularly, HPLC coupled with high resolution-mass spectrometry (HR-MS) and
multiple-stage MS (MSn
) plays a leading role in identification of metabolites (1-2).
Sample preparation, mass fragmentation studies, in silico metabolite prediction
and detection, chromatographic retention, UV spectra matching, determination of
molecular formula, and establishment of possible site of metabolism are the important
aspects in unequivocal identification of metabolites. In this same context, there
have been several recent advancements in metabolite identification. These include
approaches for detection of reactive metabolites, new generation LC systems and
MS ion sources, isotopic pattern matching, hydrogen/deuterium exchange mass
spectrometry, data dependent analyses, MSE
approach, mass defect filter, 2D and
3D approaches for elucidation of molecular formula, polarity switching, background
subtraction-noise reduction algorithms (BgS-NoRA), etc. The same will be discussed
with case examples, as appropriate.
doi:10.4172/2155-9872.1000005
ANALBIOANAL-2010
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