Biosynthesis, characterisation and direct high-performance liquid chromatographic analysis of gemfibrozil 1-O-beta-acylglucuronide

J Chromatogr B Biomed Appl. 1995 Mar 24;665(2):345-53. doi: 10.1016/0378-4347(94)00530-i.

Abstract

Gemfibrozil 1-O-beta-acylglucuronide was purified from the urine of a volunteer administered gemfibrozil, and an isocratic reversed-phase HPLC method was developed for its direct measurement. Quantitation of gemfibrozil and gemfibrozil 1-O-beta-acylglucuronide was carried out from plasma, following extraction from acidified specimens into ethyl acetate, on a 5-microns CN reversed-phase column with a mobile phase (pH 3.5) containing acetonitrile, tetrabutylammonium sulphate and distilled water, using fluorescence detection at 284 nm excitation and 316 nm emission. Calibration curves were linear for both compounds over a concentration range of 0.1 to 40 mg/l, with intra-assay coefficients of variation < 5% at concentrations of 20.0, 2.0 and 0.2 mg/l, and inter-assay coefficients of variation < 10%. No degradation of gemfibrozil 1-O-beta-acylglucuronide was detected as a result of the analytical procedure. However, a preliminary application of the method indicates that gemfibrozil acylglucuronide is chemically unstable undergoing intra-molecular rearrangement and hydrolysis under physiological conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromatography, High Pressure Liquid* / statistics & numerical data
  • Chromatography, Thin Layer
  • Drug Stability
  • Gemfibrozil / analogs & derivatives*
  • Gemfibrozil / blood
  • Gemfibrozil / metabolism*
  • Gemfibrozil / urine
  • Glucuronates / blood
  • Glucuronates / urine*
  • Humans
  • Hydrogen-Ion Concentration
  • Magnetic Resonance Spectroscopy
  • Mass Spectrometry
  • Quality Control

Substances

  • Glucuronates
  • gemfibrozil 1-O-acylglucuronide
  • Gemfibrozil