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.
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.
van Welie
R T
RT
Department of Pharmacochemistry, Free University, Amsterdam, The Netherlands.
Mensert
R
R
Van Duyn
P
P
Vermeulen
N P
NP
D000111:Acetylcysteine / Q000378:metabolism*; D000328:Adult; D000818:Animals; D002264:Carboxylic Acids / Q000378:metabolism*; D004784:Environmental Monitoring / Q000379:methods*; D005659:Fungicides, Industrial / Q000378:metabolism*; D006801:Humans; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013830:Thiadiazoles / Q000378:metabolism* / Q000633:toxicity
D002264:Carboxylic Acids; D005659:Fungicides, Industrial; D013830:Thiadiazoles; C014547:etridiazol; D000111:Acetylcysteine