The metabolism of piperidine-type phenothiazine antipsychotic agents. I. Sulforidazine in the rat
Xenobiotica, ISSN: 0049-8254, Vol: 22, Issue: 3, Page: 303-317
1992
- 9Citations
- 5Captures
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- Citations9
- Citation Indexes9
- CrossRef7
- Captures5
- Readers5
Article Description
1. The metabolism of the piperidine-type, phenothiazine antipsychotic agent, sulforidazine, was studied in female rats after a 20mg/kg single oral dose. 2. Compounds identified in urine were sulforidazine, sulforidazine ring sulphoxide, the lactam of sulforidazine, the lactam of sulforidazine ring sulphoxide, two diastereomers of N-desmethylsulforidazine ring sulphoxide and a phenolic derivative of sulforidazine. 3. Metabolites were separated by h.p.l.c. prior to mass spectrometric or g.l.c.-mass spectrometric analysis. Except in the case of the phenolic metabolite, structures were confirmed by direct comparison of electron impact mass spectra and chromatographic behaviour with those of authentic samples. To facilitate identification of the phenolic metabolite the crude urinary extract was treated with a silylating reagent and analysed by h.p.l.c.-mass spectrometry with a plasmaspray interface. 4. Despite the availability of authentic standards of sulforidazine N-oxide and sulforidazine N,S-dioxide neither of these compounds could be identified in urinary extracts obtained from rats. 5. Sulforidazine underwent extensive metabolism in rats as only 2·3±0·4% (n=5) of the dose was present as unchanged sulforidazine in 24h urine. The lactam of sulforidazine (0·1±0·1%) was a minor metabolite whereas the lactam of sulforidazine ring sulphoxide was 3·2±2·6% dose. 6. Sulforidazine sulphoxide (12·1±1·6%) was a major metabolite and its diastereomers were present in similar amounts. © 1992 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.
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