Virtual chromatographic resolution enhancement in cryoflow LC-NMR experiments via statistical total correlation spectroscopy.
A new approach to enhancing information recovery from cryogenic probe "on-flow" LC-NMR spectroscopic analyses of complex biological mixtures is demonstrated using a variation on the statistical total correlation spectroscopy (STOCSY) method. Cryoflow probe technology enables sensitive and efficient NMR detection of metabolites on-flow, and the rapid spectral scanning allows multiple spectra to be collected over chromatographic peaks containing several species with similar, but nonidentical, retention times. This enables 1H NMR signal connectivities between close-eluting metabolites to be identified resulting in a "virtual" chromatographic resolution enhancement visualized directly in the NMR spectral projection. We demonstrate the applicability of the approach for structure assignment of drug and endogenous metabolites in urine. This approach is of wide general applicability to any complex mixture analysis problem involving chromatographic peak overlap and with particular application in metabolomics and metabonomics.
Cloarec
Olivier
O
Department of Biomolecular Medicine, Division of Surgery, Oncology, Reproductive Biology and Anaesthetics, Faculty of Medicine, Imperial College London, South Kensington, London SW7 2AZ, UK.
Campbell
Alison
A
Tseng
Li-Hong
LH
Braumann
Ulrich
U
Spraul
Manfred
M
Scarfe
Graeme
G
Weaver
Richard
R
Nicholson
Jeremy K
JK
D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods / Q000592:standards / Q000706:statistics & numerical data; D009682:Magnetic Resonance Spectroscopy / Q000379:methods* / Q000592:standards / Q000706:statistics & numerical data*; D008297:Male; D015394:Molecular Structure; D051381:Rats; D017208:Rats, Wistar; D012015:Reference Standards; D012680:Sensitivity and Specificity; D013827:Thiabendazole / Q000652:urine*
D013827:Thiabendazole