Heteronuclear 19F-1H statistical total correlation spectroscopy as a tool in drug metabolism: study of flucloxacillin biotransformation

Analytical Chemistry
Hector C KeunJeremy K Nicholson

Abstract

We present a novel application of the heteronuclear statistical total correlation spectroscopy (HET-STOCSY) approach utilizing statistical correlation between one-dimensional 19F/1H NMR spectroscopic data sets collected in parallel to study drug metabolism. Parallel one-dimensional (1D) 800 MHz 1H and 753 MHz 19F{1H} spectra (n = 21) were obtained on urine samples collected from volunteers (n = 6) at various intervals up to 24 h after oral dosing with 500 mg of flucloxacillin. A variety of statistical relationships between and within the spectroscopic datasets were explored without significant loss of the typically high 1D spectral resolution, generating 1H-1H STOCSY plots, and novel 19F-1H HET-STOCSY, 19F-19F STOCSY, and 19F-edited 1H-1H STOCSY (X-STOCSY) spectroscopic maps, with a resolution of approximately 0.8 Hz/pt for both nuclei. The efficient statistical editing provided by these methods readily allowed the collection of drug metabolic data and assisted structure elucidation. This approach is of general applicability for studying the metabolism of other fluorine-containing drugs, including important anticancer agents such as 5-fluorouracil and flutamide, and is extendable to any drug metabolism study where there is a sp...Continue Reading

References

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Citations

Jul 1, 2009·Future Medicinal Chemistry·Anthony D MaherJeremy K Nicholson
Jul 22, 2015·Nature Reviews. Gastroenterology & Hepatology·Elaine HolmesJeremy K Nicholson
Jul 19, 2020·Nature Protocols·Isabel Garcia-PerezJeremy K Nicholson
Feb 7, 2018·Progress in Nuclear Magnetic Resonance Spectroscopy·Jun KikuchiYasuhiro Date
Jun 15, 2021·Molecular Omics·Vivian TountaGerald Larrouy-Maumus
Aug 21, 2014·Analytical Chemistry·Chaevien S ClendinenArthur S Edison
Apr 26, 2013·Analytical Chemistry·Steven L RobinetteJeremy K Nicholson
Sep 6, 2011·Accounts of Chemical Research·Steven L RobinetteArthur S Edison

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