URINARY METABOLITES OF THIAMINE TETRAHYDROFURFURYL DISULFIDE IN RATS

¹ Biological Research Laboratories and Chemical Research Laboratories, Research and Development Division, Takeda Chemical Industries, Ltd., Osaka, Japan

Most of the radioactivity was eliminated exclusively into the urine when thiamine tetrahydrofurfuryl disulfide-S³⁵ (outer) was fed to rats. The metabolites were isolated by chromatographic fractionation using silicic acid or a hyldietaminoethyl Sephadex anion exchanger. The isolated metabolites were compared with synthetic standards and were characterized chemically by isotope dilution, infrared analysis, nuclear magnetic resonance and mass spectrometry. About 90% of the urinary radioactivity was thus identified as -hydroxy--methylsulfonyl valerie acid (50-70%), methyl tetrahydrofurfuryl sulfoxide (15-30%), -hydroxy--methylsulfinyl valerie acid (4-7%), methyl tetrahydrofurfuryl sulfone (2-4%) and inorganic sulfate (3-6%). The hydroxy valerie acid metabolites were converted to the corresponding -lactones by treatment with acid, and the identity of the lactones was also established by spectroscopy, mass spectrometry and isotope dilution. Time course studies on metabolite pattern show that -hydroxy--methylsulfonyl valeric acid is a main and terminal product. The present studies add further evidence for the importance of the methylsulfonyl pathway in the biotransformation of foreign alkyl mercaptans.