Enzymic synthesis of two glucuronides of the hydroxyisoxazole GABA-agonist, THIP, and the in vivo glucuronidation of THIP in rat

Abstract

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 ¹³O-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.