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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.

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 (1991-01-01)
R T van Welie, R Mensert, P Van Duyn, N P Vermeulen
RESUMEN

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 micrograms/l urine (CV = 15.4%, n = 3). The detection limit of ET-CA, applying GC with sulphur selective detection (GC-FPD), was 100 micrograms/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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Supelco
Etridiazole, PESTANAL®, analytical standard
Supelco
Etridiazole, certified reference material, TraceCERT®, Manufactured by: Sigma-Aldrich Production GmbH, Switzerland