Identification of a new urinary metabolite of carbon disulfide using an improved method for the determination of 2-thioxothiazolidine-4-carboxylic acid

A new method is reported for the analysis of 2-thioxothiazolidine-4-carboxy lic acid (TTCA) in urine that is amenable to automation and provides greatl y simplified chromatograms. The method comprises the addition of tetrahydro -2-thioxo-2H-1,3-thiazine-4-carboxylic acid, which is chemically similar to TTCA, as internal standard, purification on an Oasis HLB solid-phase extra ction column, and analysis by HPLC with UV detection. The limit of detectio n for TTCA was 40 pmol/mL of urine, recovery was 79.3 +/- 1.0%, and detecti on was linear over at least 3 orders of magnitude. In addition, during the analysis of urine samples from workers exposed to CS2, a novel urinary meta bolite Of CS2 was recognized. The new metabolite demonstrated a dose respon se, was present at approximately 30% the level of TTCA, and was charaterize d to be 2-thioxothiazolidin-4-ylcarbonylglycine (TTCG). Administration of T TCG to rats resulted in excretion of TTCA suggesting that TTCG is a likely precursor of TTCA. Although urinary excretion of both TTCA and TTCG resulte d from administration of captan, only TTCA was detected following administr ation of methyl isothiocyanate. The greater selectivity of TTCG suggests th at co-analysis of TTCA and TTCG in urine may aid in differentiating exposur es to CS2, captan and isothiocyanates.