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High‐throughput, accurate mass liquid chromatography/tandem mass spectrometry on a quadrupole time‐of‐flight system as a ‘first‐line’ approach for metabolite identification studies
Author(s) -
Tiller Philip R.,
Yu Sean,
CastroPerez Jose,
Fillgrove Kerry L.,
Baillie Thomas A.
Publication year - 2008
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/rcm.3472
Subject(s) - chemistry , metabolite , quadrupole time of flight , mass spectrometry , tandem mass spectrometry , chromatography , tandem , metabolomics , biotransformation , liquid chromatography–mass spectrometry , drug discovery , identification (biology) , computational biology , biochemistry , materials science , botany , composite material , biology , enzyme
Throughput for drug metabolite identification studies has been increased significantly by the combined use of accurate mass liquid chromatography/tandem mass spectrometry (LC/MS/MS) data on a quadrupole time‐of‐flight (QTOF) system and targeted data analysis procedures. Employed in concert, these tools have led to the implementation of a semi‐automated high‐throughput metabolite identification strategy that has been incorporated successfully into lead optimization efforts in drug discovery. The availability of elemental composition data on precursor and all fragment ions in each spectrum has greatly enhanced confidence in ion structure assignments, while computer‐based algorithms for defining sites of biotransformation based upon mass shifts of diagnostic fragment ions have facilitated identification of positions of metabolic transformation in drug candidates. Adoption of this technology as the ‘first‐line’ approach for in vitro metabolite profiling has resulted in the analysis of as many as 21 new chemical entities on one day from diverse structural classes and therapeutic programs. Copyright © 2008 John Wiley & Sons, Ltd.