IDENTIFICATION OF METABOLITES OF AZAPERONE IN HORSE URINE

Two metabolites of the tranquilizer azaperone were extracted from alka linized horse urine after treatment with beta-glucuronidase/sulfatase from limpets (Patella vulgata). The metabolites were identified by a c ombination of independent chemical synthesis and GC/MS and H-1 NMR ana lysis. The metabolites were identified as nyl)-4-[4-(5-hydroxy-2-pyrid inyl)-1-piperazinyl]-1 -butanol, designated as 5'-hydroxyazaperol, and 1-(fluorophenyl)-4-[4-(5-hydroxy-2-pyridinyl)-1 -piperazinyl]-1-butan one, designated as 5'-hydroxyazaperone. A TLC screening test was devel oped for detecting both metabolites in basic extracts of horse urine t reated with beta-glucuronidase/sulfatase. The screening test was used to detect azaperone metabolites in extracts of horse urine collected f or 24 h after intravenous administration of azaperone. The administrat ion of azaperone to horses was confirmed by GC/MS identification of 5' -hydroxyazaperone and 5'-hydroxyazaperol from basic extracts of horse urine treated with beta-glucuronidaseisulfatase. The extracted metabol ites were treated with bis(trimethylsilyl)acetamide to produce trimeth ylsilyl (TMS) ether derivatives, and mass spectra and retention times were compared to those of the synthesized metabolites treated in the s ame manner.