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Archives of Toxicology

, Volume 65, Issue 8, pp 625–632 | Cite as

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

  • R. T. H. Van Welie
  • R. Mensert
  • P. Van Duyn
  • N. P. E. Vermeulen
Original Investigations

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.

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 

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Copyright information

© Springer-Verlag 1991

Authors and Affiliations

  • R. T. H. Van Welie
    • 1
  • R. Mensert
    • 1
  • P. Van Duyn
    • 1
  • N. P. E. Vermeulen
    • 1
  1. 1.Department of Pharmacochemistry Division of Molecular ToxicologyFree UniversityHV AmsterdamThe Netherlands

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