The Fate of Saccharin Impurities the Excretion and Metabolism of [¹⁴C]Toluene-4-sulphonamide and 4-Sulphamoyl[¹⁴C]benzoic Acid in the Rat

Abstract

1. 4-Sulphamoyl[carboxy-¹⁴C]benzoic acid was rapidly eliminateda after oral administration to rats (94% dose in 24 h). After 6 days most of the ¹⁴C (73-83% dose) was recovered in the urine with significant amounts (18-32% dose) in the faeces due to incomplete absorption.

2. The ¹⁴C in the urine and faeces was unchanged 4-sulphamoylbenzoic acid. No ¹⁴CO₂ was detected in the expired air.

3. After oral administration of [methyl-¹⁴C]toluene-4-sulphonamide to rats the label was rapidly eliminated largely in the urine (66-89% dose) with little in the faeces (2-8% dose). The ¹⁴C in the faeces was 4-sulphamoylbenzoic acid, which probably originated in the tissues since the gut flora was unable to effect this biotransformation.

4. The urine of rats given [¹⁴C]toluene-4-sulphonamide contained 4-sulphamoylbenzoic acid as the major metabolite (93% of the urinary ¹⁴C) together with small amounts of unchanged compound (1.5-2.3% of urinary ¹⁴C), 4-sulphamoylbenzyl alcohol (2.0-3.9%), 4-sulphamoylbenzaldehyde (0-1.5%) and at higher doses N-acetyltoluene-4-sulphonamide (2.1-2.3%).