TY - JOUR
T1 - EC–SPE–stripline-NMR analysis of reactive products: A feasibility study.
AU - Falck, D.
AU - Oosthoek-de Vries, A.J.
AU - Kolkman, A.J.
AU - Lingeman, H.
AU - Honing, M.
AU - Wijmenga, S.S.
AU - Kentgens, A.P.M.
AU - Niessen, W.M.A.
PY - 2013
Y1 - 2013
N2 - Flow-through electrochemical conversion (EC) of drug-like molecules was hyphenated to miniaturized nuclear magnetic resonance spectroscopy (NMR) via on-line solid-phase extraction (SPE). After EC of the prominent p38α mitogen-activated protein kinase inhibitor BIRB796 into its reactive products, the SPE step provided preconcentration of the EC products and solvent exchange for NMR analysis. The acquisition of NMR spectra of the mass-limited samples was achieved in a stripline probe with a detection volume of 150 nL offering superior mass sensitivity. This hyphenated EC-SPE-stripline-NMR setup enabled the detection of the reactive products using only minute amounts of substrate. Furthermore, the integration of conversion and detection into one flow setup counteracts incorrect assessments caused by the degradation of reactive products. However, apparent interferences of the NMR magnetic field with the EC, leading to a low product yield, so far demanded relatively long signal averaging. A critical assessment of what is and what is not (yet) possible with this approach is presented, for example in terms of structure elucidation and the estimation of concentrations. Additionally, promising routes for further improvement of EC-SPE-stripline-NMR are discussed. © 2013 Springer-Verlag Berlin Heidelberg.
AB - Flow-through electrochemical conversion (EC) of drug-like molecules was hyphenated to miniaturized nuclear magnetic resonance spectroscopy (NMR) via on-line solid-phase extraction (SPE). After EC of the prominent p38α mitogen-activated protein kinase inhibitor BIRB796 into its reactive products, the SPE step provided preconcentration of the EC products and solvent exchange for NMR analysis. The acquisition of NMR spectra of the mass-limited samples was achieved in a stripline probe with a detection volume of 150 nL offering superior mass sensitivity. This hyphenated EC-SPE-stripline-NMR setup enabled the detection of the reactive products using only minute amounts of substrate. Furthermore, the integration of conversion and detection into one flow setup counteracts incorrect assessments caused by the degradation of reactive products. However, apparent interferences of the NMR magnetic field with the EC, leading to a low product yield, so far demanded relatively long signal averaging. A critical assessment of what is and what is not (yet) possible with this approach is presented, for example in terms of structure elucidation and the estimation of concentrations. Additionally, promising routes for further improvement of EC-SPE-stripline-NMR are discussed. © 2013 Springer-Verlag Berlin Heidelberg.
U2 - 10.1007/s00216-013-7158-9
DO - 10.1007/s00216-013-7158-9
M3 - Article
SN - 1618-2642
VL - 405
SP - 6711
EP - 6720
JO - Analytical and Bioanalytical Chemistry
JF - Analytical and Bioanalytical Chemistry
ER -
