Identification of glyburide metabolites formed by hepatic and placental microsomes of humans and baboons

Biochem Pharmacol. 2006 Dec 15;72(12):1730-7. doi: 10.1016/j.bcp.2006.08.024. Epub 2006 Aug 30.


Glyburide (glibenclamide) is a second-generation sulfonylurea used for treatment of type-2 and gestational diabetes mellitus. To date, two glyburide metabolites have been identified in maternal urine: namely, 4-trans-hydroxycyclohexyl glyburide and 3-cis-hydroxycyclohexyl glyburide. The use of glyburide to treat gestational diabetes prompted us to investigate its metabolism by the placenta. The metabolism of glyburide by microsomal preparations from human and baboon placenta was compared with metabolism by their livers. The metabolites formed by the microsomes of the four tissues were identified by high-performance liquid chromatography-mass spectrometry using retention times, ion current (extracted at m/z 510), and selected-ion monitoring. The data obtained revealed the formation of six distinct hydroxylated derivatives of glyburide by each of the four microsomal preparations. However, the amounts of the six metabolites formed by the placentas were a fraction of that formed by the livers. Moreover, the relative quantities of each metabolite formed differed between species as well as between the two tissues. Also, the structure of the unidentified metabolites was determined by comparison with synthesized standards. These metabolites were identified as the 4-cis-hydroxycyclohexyl glyburide, 3-trans-hydroxycyclohexyl glyburide, and 2-trans-hydroxycyclohexyl glyburide. Therefore, one glyburide metabolite remains to be identified, but the data we obtained allowed us to suggest its structure.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Animals
  • Biotransformation
  • Chromatography, High Pressure Liquid
  • Female
  • Glyburide / metabolism*
  • Glyburide / pharmacology
  • Humans
  • Hypoglycemic Agents / metabolism*
  • Hypoglycemic Agents / pharmacology
  • In Vitro Techniques
  • Liver / drug effects
  • Liver / metabolism*
  • Male
  • Mass Spectrometry
  • Microsomes / drug effects
  • Microsomes / metabolism*
  • Microsomes, Liver / drug effects
  • Microsomes, Liver / metabolism
  • Middle Aged
  • Molecular Structure
  • Organ Specificity
  • Placenta / drug effects
  • Placenta / metabolism*
  • Species Specificity


  • Hypoglycemic Agents
  • Glyburide