FURTHER STUDIES ON THE URINARY METABOLITES OF THIAMINE PROPYL DISULFIDE IN RATS

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

Of the radioactivity excreted in the urine of rats fed thiamine propyl disulfide-S³⁵ (outer), about 40% was found in the acidic fractions and identified as methylsulfonyl propionic acid and inorganic sulfate after chromatographic separations. The identification of methylsulfonyl propionic acid was accomplished by infrared, nuclear magnetic resonance and mass spectrometry as well as isotope dilution with authentic samples of the acid and its methyl ester. The present metabolites, together with the already characterized ones, methyl propyl sulfone and 2- and 3-hydroxypropyl methyl sulfone, accounted for more than 90% of the urinary radioactivity. A standardized method was established for determination of these metabolites under various dosage regimens. The S-propyl moiety of thiamine propyl disulfide was rapidly and almost quantitatively excreted in the urine after conversion to the methylsulfonyl compounds or sulfate. Among these metabolites, 2-hydroxypropyl methyl sulfone, methylsulfonyl propionic acid and sulfate were the major products. The fate of S³⁵-labeled methyl propyl sulfone, 2- and 3-hydroxypropyl methyl sulfone were also studied. Radioactive inorganic sulfate was not produced from these compounds. All of these results demonstrated the occurrence of two distinct metabolic pathways responsible for the formations of inorganic sulfate and the methylsulfonyl compounds, respectively. The implications of the new pathway involving 5-methylation and sulfoxidation are discussed in connection with the biotransformation of foreign alkyl mercaptans.