TY - JOUR T1 - Metabolism of the antianxiety drug buspirone in the rat. JF - Drug Metabolism and Disposition JO - Drug Metab Dispos SP - 625 LP - 633 VL - 17 IS - 6 AU - H K Jajoo AU - R F Mayol AU - J A LaBudde AU - I A Blair Y1 - 1989/11/01 UR - http://dmd.aspetjournals.org/content/17/6/625.abstract N2 - The metabolism of an orally administered, 10-mg single dose of the antianxiety drug buspirone was studied in the rat. Samples of bile and urine were collected for 6 hr and were treated with beta-glucuronidase/arylsulfatase. The deconjugated metabolites were isolated and purified by HPLC. Structural analysis was carried out by combined gas chromatography/electron impact mass spectrometry as their trimethylsilyl derivatives and by 1H-NMR spectroscopy. Structures of the metabolites were further confirmed by co-elution on HPLC with authentic standards when possible. In addition to the already known metabolites 5-hydroxy-buspirone and 1-pyrimidinylpiperazine, seven major metabolites were unambiguously identified together with unchanged drug. Ten minor metabolites were partially characterized. Hydroxylation alpha to the glutaramidyl carbon at the 6'-position on the bicyclo ring system, hydroxylation on the pyrimidine aromatic ring, and N-dealkylation of the butyl side chain were observed as major routes of metabolism. Minor routes of metabolism observed were: 3'-hydroxylation on the bicyclo ring system and formation of the methylated catechol derivatives. The identified metabolites accounted for greater than 90% of the total metabolites excreted in the rat bile and urine samples. ER -