The Fate of Saccharin Impurities: The Metabolism and Excretion of 3-Amino [3-¹⁴C]benz[d]-isothiazole-1,1-dioxide and 5-Chlorosaccharin in the Rat

Abstract

1. 3-Amino[3-¹⁴C]benz[d]isothiazole-1,1-dioxide was prepared from [3-¹⁴C]-saccharin. It was well absorbed on oral administration to rats (25 mg/kg) with only 2% of the ¹⁴C in the faeces. The absorbed material was rapidly eliminated with about 87% dose in the urine in 24 h and 91% in 4 days. Little ¹⁴C (0·5% of dose) was present in the carcass 4 days after dosing. Most of the ¹⁴C in the 0-24 h urine (99%) was present as unchanged 3-aminobenz[d]isothiazole-1,1-dioxide, the rest being an unidentified metabolite.

2. 5-Chlorosaccharin was excreted unchanged after oral administration to rats (80 mg/kg) with 76% dose in the urine in 24 h and 81% in 4 days. Only 4% was detected in the faeces. There was no significant hydrolysis (<0·5%) to 5-chloro-2-sulphamoylbenzoic acid.

3. The extent of metabolism of these and other compounds related to saccharin showed good agreement with the extent of their partitioning into organic solvents.