METABOLISM OF PROPYNYL)OXY]PHENYL]-3,4,5,6-TETRAHYDROPHTHALIMIDE (S-23121) IN THE RAT .1. IDENTIFICATION OF A NEW, SULFONIC-ACID TYPE OF CONJUGATE

1. Several metabolites of C-14-labelled ropynyl)oxy]phenyl]-3,4,5,6-te tra-hydrophthalimide (S-23121) were identified. 2. The major urinary m etabolites were found to be 4-chloro-2-fluoro-5-hydroxyaniline, its su lphate and glucuronide by t.l.c. cochromatography with authentic stand ards. 3. The major faecal metabolites in addition to the parent compou nd were six sulphonic acid conjugates having a sulphonic acid group in corporated into the double bond of the 3,4,5,6-tetrahydrophthalimide m oiety. These sulphonic acid conjugates have never been reported previo usly for this type of compound. 4. To confirm the mechanism of biosynt hesis of the sulphonic acid conjugates, sodium sulphate, cysteine and glutathione labelled with S-35 were administered to the male rat toget her with unlabelled S-23121. The same faecal metabolites as those dete cted in faeces of the rat dosed with C-14-labelled S-23121 were simila rly found after dosing with any of the S-35-labelled chemicals. Their biosynthesis was most pronounced with S-35-labelled sodium sulphate, i mplying that the sulphonic acid is incorporated into the double bond a fter reduction of sulphate to sulphite.