APPARENT INTRAMOLECULAR ACYL MIGRATION OF ZOMEPIRAC GLUCURONIDE

  • 1 January 1982
    • journal article
    • research article
    • Vol. 10  (5) , 469-473
Abstract
For the antiinflammatory drug zompirac (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 unstable at physiological pH, leading to 4 compounds other than Z. ZG and the other fractions were purified from [human] urine by preparative HPLC [high-performance liquid chromatography] 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.degree. C in H2O; maximum stability was found at pH 2. Intramolecular acyl migration of the glucuronide is postulated, as 4 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.