Enzymic synthesis of two glucuronides of the hydroxyisoxazole GABA-agonist, THIP, and the in vivo glucuronidation of THIP in rat.
1. A method for preparative enzymic synthesis of two glucuronides of THIP (3-hydroxy-4,5,6,7-tetrahydro-isoxazolo[5,4-c]pyridine) is described. 2. Using FAB mass spectrometry, u.v. and 1H- and 13C-n.m.r. spectroscopy, the two glucuronides were identified as N- and O-glucuronides respectively. 3. An h.p.l.c. method for determination of THIP and the two intact glucuronides in urine has been developed. 4. The glucuronidation pattern of THIP in rats has been examined; THIP was excreted as a THIP-O-glucuronide but not as a THIP-N-glucuronide.
Andersen
J V
JV
Royal Danish School of Pharmacy, Department of Organic Chemistry, Copenhagen, Denmark.
Dalgaard
L
L
Hansen
S H
SH
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D005965:Glucuronates / Q000378:metabolism / Q000652:urine; D005966:Glucuronidase / Q000378:metabolism; D006868:Hydrolysis; D007555:Isoxazoles / Q000378:metabolism* / Q000652:urine; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000378:metabolism*; D010080:Oxazoles / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D013056:Spectrophotometry, Ultraviolet
D005965:Glucuronates; D007555:Isoxazoles; D010080:Oxazoles; D005966:Glucuronidase; C015542:gaboxadol