Metabolomic applications of electrochemistry/mass spectrometry.
Analytical techniques used for multivariate analysis of endogenous metabolites in biological systems (e.g., metabolomics, metabonomics) must be capable of accurately and selectively monitoring many known and unknown molecules that span a diverse chemical spectrum and over extremely large dynamic concentration ranges. Mass spectrometric (MS) and electrochemical array (EC-Array) detection have been widely used for multi-component analysis with applicability to low-level (fmol) metabolites. Described here are practical considerations and results obtained with the combined use of EC-Array and MS for HPLC-based multivariate metabolomic analysis. Data presented include the study of changes in rat urinary metabolite profiles associated with xenobiotic toxin exposure analyzed by HPLC using water:acetonitrile binary gradient conditions and post-column flow splitting between EC-Array and MS detectors. Results show complementary quantitative and qualitative analysis and the ability to differentiate sample groups consistent with xenobiotic-induced histopathological changes. The potential applicability of this hyphenated technique for biomarker elucidation through measurement of redox active compounds that are commonly associated with disease pathology and xenobiotic toxicity is discussed. The use of EC reactor cells in series with MS is also presented as a means of producing likely metabolites to facilitate structural elucidation and confirmation.
Gamache
Paul H
PH
ESA Inc., 22 Alpha Road, Chelmsford, MA 01824, USA. pgamache@esainc.com
Meyer
David F
DF
Granger
Michael C
MC
Acworth
Ian N
IN
D000818:Animals; D004563:Electrochemistry / Q000379:methods*; D008297:Male; D008660:Metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
D004364:Pharmaceutical Preparations