IDENTIFICATION AND GAS-CHROMATOGRAPHIC DETERMINATION OF SOME CARBOXYLIC-ACID METABOLITES OF N,N-DIETHYL-M-TOLUAMIDE IN RAT URINE

Adult Wistar rats dosed intraperitoneally and topically (50 mg/kg) with N,N-diethyl-m-toluamide (1) excreted m-[(diethylamino)carbonyl]benzoic acid (3), m-[(ethylamino)carbonyl]benzoic acid (6), m-(ami-nocarbonyl)benzoic acid (9), and m-toluic acid (10) in their urine. These carboxylic acids were isolated by extraction of acidified urine samples with ethyl acetate and were detected as their methyl esters by GC and GC-MS. A quantitative analytical procedure, based on GC with a nitrogen-phos-phorus detector, a capillary column of DB-1, and an internal standard of m-[(dipropylamino)carbonyl] benzoic acid (13), was developed to determine 3 and 6 in urine samples from treated rats. After 24 h, these major metabolites together accounted for 77% and 82% of the intraperitoneally administered dose in separate experiments with four male rats per experiment. In trials with 1 applied topically, 3 and 6 collectively represented 47% (males) and 49% (females) of the dose in 0-48-h urine collections. In the topical experiments, 5-6% of 1 was excreted unchanged. © 1990, American Chemical Society. All rights reserved.