Metabolism of SFZ-47 in chicken embryo by liquid chromatography-electrospray ion trap mass spectrometry

Acta Pharmacol Sin. 2003 Jun;24(6):576-80.

Abstract

Aim: To develop an alternative method for investigation of drug metabolism by fertilized chicken eggs using 3H-1,2-dihydro-2-(4-methyl-phenylamino) methyl-1-pyrrolizinone (SFZ-47) as a probe drug.

Methods: SFZ-47 (15 mg) was injected into the albumen of eggs from standardized breed chickens previously incubated for 10 d. After 72 h of further incubation, the allantoic liquid was subjected to solid phase extraction on XAD-2 columns and analyzed by liquid chromatography-electrospray ion trap mass spectrometry method.

Results: Three major metabolites were identified, namely 4-(3H-1,2-dihydro-1-pyrrolizinone-2-methyl-amino) benzyl alcohol (SFZ-47-OH), 4-(3H-1,2-dihydro-1-pyrrolizinone-2-methyl-amino)-benzoic acid (SFZ-47-COOH), and its glucuronide conjugates. The metabolic profile was little different from that previously found in rabbits and dogs.

Conclusion: The result demonstrates the usefulness of the fertilized chicken egg as a convenient source of both phase I and phase II metabolites for further metabolism studies of SFZ-47.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chick Embryo
  • Chromatography, Liquid
  • Pyrroles / metabolism*
  • Spectrometry, Mass, Electrospray Ionization

Substances

  • 3H-1,2-dihydro-2-(4-methylphenylamino)methyl-1-pyrrolizinone
  • Pyrroles