A validated HPLC-MS/MS method for determination of genipin-1-o-glucuronic acid in rat plasma after administration of genipin and its application to a pharmacokinetic study

Biomed Chromatogr. 2014 Feb;28(2):265-74. doi: 10.1002/bmc.3017. Epub 2013 Sep 4.

Abstract

A sensitive and specific method was developed and validated for the quantitation of one major metabolite of genipin in rats plasma. The major metabolite was isolated from rat bile via semi-preparative HPLC technology and its chemical structure was identified as genipin-1-o-glucuronic acid (GNP-GLU), which was for the first time used as a standard compound for quantitative analysis in rat plasma after administration of genipin. The application of high-performance liquid chromatography-tandem mass spectrometry in negative mode in multiple reaction monitoring mode was investigated. Chromatographic separation was achieved on an Eclipse XDB-C18 column using a mobile phase consisting of water with 0.1% formic acid (A)-acetonitrile (B). The limit of detecation was 0.214 ng/mL and the lower limit of quantification was 0.706 ng/mL. The calibration curve was linear from 1.27 to 3810 ng/mL for plasma samples, with a correlation coefficient of 0.9924. The intra- and inter-day precisions and accuracy were all within 15%. The recoveries of GNP-GLU and puerarin were above 90.0 and 76.2%, respectively. The highly sensitive method was successfully applied to estimate pharmacokinetic parameters of GNP-GLU following oral and intravenous administration of genipin to rats.

Keywords: genipin; genipin-1-o-glucuronic acid; liquid chromatography-tandem mass spectrometry; pharmacokinetic study.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromatography, High Pressure Liquid / methods*
  • Drug Stability
  • Glucuronic Acid
  • Iridoids / administration & dosage
  • Iridoids / blood*
  • Iridoids / chemistry
  • Iridoids / pharmacokinetics*
  • Limit of Detection
  • Linear Models
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Reproducibility of Results
  • Tandem Mass Spectrometry / methods*

Substances

  • Iridoids
  • Glucuronic Acid
  • genipin