Determination of urinary metabolites of thiamine propyl disulfide in humans.

Abstract

Gas chromatographic procedure for the quantitative determination of methyl propyl sulfone (MPS), 2-hydroxypropyl methyl sulfone (2HPMS) and 3-hydroxypropyl methyl sulfone (3HPMS) in urine was developed. By using this procedure, the urinary excretion of MPS, 2HPMS and 3HPMS after oral dose of thiamine propyl disulfide (TPD) was investigated in healthy adults, in order to assess their ability of drug disposition including metabolism. Among these metabolites, 2HPMS was predominant and the other two were minor. 2HPMS was excreted most in the 24--36 h urine and the time course of excretion of this metabolite was almost the same among these subjects. In 4th day urine, a significant amount of 2HPMS was still excreted. On the contrary, the time course of excretion of MPS varied among subjects and also at different occasions in the same subjects. 3HPMS was excreted most in the 0--12 or 12--24 h urine and more rapidly excreted than 2HPMS. Two-fold interindividual differences in the amount of 2HPMS in the 0--48 h urine occurred and intraindividual difference was also observed. Inter- and intraindividual differences in the amount of MPS in 0--48 h urine were much larger than that in 2HPMS. In 3HPMS, these differences were slightly less than in 2HPMS. Sex difference in the excretion of MPS and 2HPMS was not observed.