PT - JOURNAL ARTICLE AU - J Hasegawa AU - P C Smith AU - L Z Benet TI - Apparent intramolecular acyl migration of zomepirac glucuronide. DP - 1982 Sep 01 TA - Drug Metabolism and Disposition PG - 469--473 VI - 10 IP - 5 4099 - http://dmd.aspetjournals.org/content/10/5/469.short 4100 - http://dmd.aspetjournals.org/content/10/5/469.full SO - Drug Metab Dispos1982 Sep 01; 10 AB - For the antiinflammatory drug zomepirac (Z), 5-(4-chlorobenzoyl)-1,4-dimethyl-1H-pyrrole-2 acetic acid, the glucuronic acid conjugate (ZG) is the major metabolite. During analytical development ZG was found to be unstable at physiological pH, leading to four compounds other than Z. ZG and the other fractions were purified from urine by preparative HPLC and the structure of ZG was confirmed by elemental analysis and by NMR and mass spectrometry. Fast atom bombardment mass spectrometry was used to analyze the unstable, underivatized acyl glucuronides. ZG was cleaved by beta-glucuronidase but the other fractions were not. The stability of ZG was determined over a pH range of 1-8; the half-life was 27 min at pH 7.4 and 37 degrees C in water; maximum stability was found at pH 2. Intramolecular acyl migration of the glucuronide is postulated, as four of the isolated fractions formed from ZG yielded a mass-spectral parent ion corresponding to ZG+ H. The importance of sample handling prior to analysis to avoid acyl migration is emphasized.