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Identification and quantitative determination of a carboxylic and a mercapturic acid metabolite of etridiazole in urine of rat and man. Potential tools for biological monitoring

Archives of Toxicology volume 65, pages 625–632 (1991)Cite this article

Abstract

Etridiazole, 5-ethoxy-3-trichloromethyl-1,2,4-thiadiazole, was orally administered to rats and human volunteers. Two metabolites of etridiazole were synthesized: 5-ethoxy-1,2,4-thiadiazole-3-carboxylic acid (ET-CA) and N-acetyl-S-(5-ethoxy-1,2,4-thiadiazol-3-yl-methyl)-l-cysteine (ET-MA). Selective and sensitive analytical procedures to determine etridiazole, the carboxylic acid ET-CA and the mercapturic acid ET-MA in urine were developed. The detection limit of etridiazole, applying GC with nitrogen selective detection (GC-NPD), was 36 (μg/l urine (CV=15.4%,n=3). The detection limit of ET-CA, applying GC with sulphur selective detection (GC-FPD), was 100 μg/l urine (CV=9.8%,n=3). In urine of rats orally treated with etridiazole, ET-CA and ET-MA were identified as metabolites of etridiazole, whereas in urine of humans given oral etridiazole, only ET-CA was identified. Unmetabolized etridiazole was excreted for less than 0.1% of the administered dose in rats. ET-CA, however, accounted for 22±9% of the administered dose of etridiazole in rats and for 13±6% in humans. ET-MA appeared to be a minor urinary metabolite of etridiazole. ET-CA is proposed as a possible biomarker for the biological monitoring of etridiazole.

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Affiliations

  1. Department of Pharmacochemistry Division of Molecular Toxicology, Free University, De Boelelaan 1083, 1081, HV Amsterdam, The Netherlands

    R. T. H. Van Welie, R. Mensert, P. Van Duyn & N. P. E. Vermeulen

Authors
  1. R. T. H. Van Welie
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  2. R. Mensert
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  3. P. Van Duyn
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  4. N. P. E. Vermeulen
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Van Welie, R.T.H., Mensert, R., Van Duyn, P. et al. Identification and quantitative determination of a carboxylic and a mercapturic acid metabolite of etridiazole in urine of rat and man. Potential tools for biological monitoring. Arch Toxicol 65, 625–632 (1991). https://doi.org/10.1007/BF02098027

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  • DOI: https://doi.org/10.1007/BF02098027

Key words

  • Etridiazole
  • N-acetyl-S-(5-ethoxy-1,2,4-thiadiazol-3-yl-methyl)-l-cysteine
  • 5-ethoxy-1,2,4-thiadiazole-3-carboxylic acid
  • Mercapturic acid
  • Biological monitoring