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A new approach to aid the characterisation and identification of metabolites of a model drug; partial isotope enrichment combined with novel formula elucidation software
Author(s) -
Hobby Kirsten,
Gallagher Richard T.,
Caldwell Patrick,
Wilson Ian D.
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.3863
Subject(s) - chemistry , isotope , mass spectrometry , metabolite , software , stable isotope ratio , identification (biology) , set (abstract data type) , combinatorial chemistry , biological system , analytical chemistry (journal) , computational biology , chromatography , computer science , biochemistry , physics , botany , quantum mechanics , biology , programming language
This work describes the identification of ‘isotopically enriched’ metabolites of 4‐cyanoaniline using the unique features of the software package ‘Spectral Simplicity’. The software is capable of creating the theoretical mass spectra for partially isotope‐enriched compounds, and subsequently performing an elemental composition analysis to give the elemental formula for the ‘isotopically enriched’ metabolite. A novel mass spectral correlation method, called ‘FuzzyFit’, was employed. ‘FuzzyFit’ utilises the expected experimental distribution of errors in both mass accuracy and isotope pattern and enables discrimination between statistically probable and improbable candidate formulae. The software correctly determined the molecular formulae of ten previously described metabolites of 4‐cyanoaniline confirming the technique of partial isotope enrichment can produce results analogous to standard methodologies. Six previously unknown species were also identified, based on the presence of the unique ‘designer’ isotope ratio. Three of the unknowns were tentatively identified as N‐acetylglutamine, O‐methyl‐N acetylglucuronide and a putative fatty acid conjugate. The discovery of a significant number of unknown species of a model drug with a comprehensive history of investigation highlights the potential for enhancement to the analytical process by the use of ‘designer’ isotope ratio compounds. The ‘FuzzyFit’ methodology significantly aided the elucidation of candidate formulae, by provision of a vastly simplified candidate formula data set. Copyright © 2008 John Wiley & Sons, Ltd.