Phenolic metabolites of chlorprothixene in man and dog

From urine and feces of dogs and urine of patients given chlorprothixene (CPT) per os, metabolites were extracted without or with enzymatic deconjugation and separated by repeated TLC. Purified compounds were characterized by UV, NMR, and mass spectrometry, by color reactions, and by chemical interconversions. Both species excreted 6- and 7-hydroxy-CPT besides the sulfoxide and demethylated analogues. In urine, the phenols were largely present as conjugates. The major metabolites in dog feces were 5-hydroxy-CPT and its demethylated derivative, whereas 5-hydroxylation was not detected in man. Dog excrete also contained 6-hydroxy-7-methoxy (or 7-hydroxy-6-methoxy)-CPT; further, a 5-hydroxy compound was detected in which the exocyclic double bond was hydrated. In the other metabolites, the Z-configuration of CPT had been retained, but small quantities of E-isomers were formed during isolation. According to preliminary quantitative data, phenols accounted for a small part of extractable metabolites in human urine, whereas they predominated in dog feces.