title: Identification of a new urinary metabolite of carbon disulfide using an improved method for the determination of 2-thioxothiazolidine-4-carboxylic acid.
abstract: A new method is reported for the analysis of 2-thioxothiazolidine-4-carboxylic acid (TTCA) in urine that is amenable to automation and provides greatly 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 extraction column, and analysis by HPLC with UV detection. The limit of detection for TTCA was 40 pmol/mL of urine, recovery was 79.3 +/- 1.0%, and detection was linear over at least 3 orders of magnitude. In addition, during the analysis of urine samples from workers exposed to CS(2), a novel urinary metabolite of CS(2) was recognized. The new metabolite demonstrated a dose response, was present at approximately 30% the level of TTCA, and was charaterized to be 2-thioxothiazolidin-4-ylcarbonylglycine (TTCG). Administration of TTCG to rats resulted in excretion of TTCA suggesting that TTCG is a likely precursor of TTCA. Although urinary excretion of both TTCA and TTCG resulted from administration of captan, only TTCA was detected following administration of methyl isothiocyanate. The greater selectivity of TTCG suggests that co-analysis of TTCA and TTCG in urine may aid in differentiating exposures to CS(2), captan and isothiocyanates.
authors.affiliation: Department of Pathology and Center in Molecular Toxicology, Vanderbilt University Medical Center, Nashville, Tennessee 37232-2561, USA. venkataraman.amarnath@mcmail.vanderbilt.edu
authors.forename: V
authors.initials: V
authors.lastname: Amarnath
authors.forename: K
authors.initials: K
authors.lastname: Amarnath
authors.forename: D G
authors.initials: DG
authors.lastname: Graham
authors.forename: Q
authors.initials: Q
authors.lastname: Qi
authors.forename: H
authors.initials: H
authors.lastname: Valentine
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: W M
authors.initials: WM
authors.lastname: Valentine
mesh_terms: D000818:Animals; D001331:Automation; D002246:Carbon Disulfide / Q000378:metabolism* / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity; D013844:Thiazoles / Q000652:urine*; D013871:Thiones / Q000652:urine*; D016482:Urinalysis / Q000379:methods
chemical_list: D013844:Thiazoles; D013871:Thiones; C117165:raphanusamic acid; D002246:Carbon Disulfide