Determination of urinary 2-thiazolidinethione-4-carboxylic acid after exposure to alkylene bisdithiocarbamates using gas chromatography–mass spectrometry

Abstract

This is a newly developed method which permits the quantitative determination of 2-thiazolidinethione-4-carboxylic acid (TTCA, an established biomarker of exposure to CS 2) as a metabolite of alkylene bisdithiocarbamates (ABDCs) in human urine. After separation of TTCA from the urinary matrix using liquid–liquid extraction the analyte was converted into its diethyl derivative. Separation and quantitative analysis was carried out by capillary gas chromatography and mass selective detection in single ion monitoring mode. 4-(4-Chloro-2-methylphenoxy)butanoic acid (MCPBA) served as internal standard. The detection limit was 0.7 μg/l in urine. The relative standard deviation of the within-series imprecision was 4.3% at a concentration of 13 μg/l. The relative recovery was within the range of 86 to 98%. In order to determine the suitability of TTCA for biological monitoring after exposure to ABDCs, we analysed 87 24-h urine samples from occupationally exposed workers. The results were compared with the levels of TTCA excreted in urine by 50 control persons without known exposure to dithiocarbamates or CS 2. This collective of unexposed persons also provided TTCA reference values for the general population. The urinary TTCA concentrations of the exposed persons were in the range from 0.8 μg/g creatinine to 515 μg/g creatinine. Unexposed persons excreted TTCA in concentrations from below the detection limit to 182 μg/g creatinine. The median concentration found in exposed persons (27 μg/g) was nearly 2.5 times higher than in non-exposed persons (11 μg/g). The difference between the exposed and unexposed collective was highly significant. Assessment of an individual’s exposure by determining the level of TTCA in urine nevertheless was not possible. This was due to the relatively wide range of concentrations and because the ranges of both collectives overlapped.