ABSTRACT
The importance of NMR spectroscopy as a tool to investigate metabolic events in vitro and in vivo becomes more and more evident. Particularly 13C-NMR spectroscopy is able to deliver a wide range of information regarding the chemistry of xenobiotics in vivo. We studied the N-demethylation of N-methyl-13C-labelled antipyrine using an isolated perfused rat liver with a fluorocarbon suspension (FC 43) as oxygen carrier. Bile was collected in different fractions during the experiment. On the vascular side metabolite formation was monitored by continuous flow NMR spectroscopy. In bile the metabolic events were detected by standard NMR techniques. The bile spectra exhibit, among others, a signal at 84.2 ppm, indicating formaldehyde hydrate derived from the N-methyl group of antipyrine by an oxidative metabolic pathway. Neither formaldehyde hydrate nor other oxidation products could be detected in the vascular perfusate. The biliary excretion of considerable amounts of formaldehyde during the N-demethylation of antipyrine might have toxicological consequences for the intra- and extrahepatic bile ducts.
