A Rapid UPLC-MS Method for Quantification of Gomisin D in Rat Plasma and Its Application to a Pharmacokinetic and Bioavailability Study

Molecules. 2019 Apr 10;24(7):1403. doi: 10.3390/molecules24071403.

Abstract

Gomisin D, a lignan compound isolated from Fructus Schisandra, is a potential antidiabetic and anti-Alzheimer's agent. Recently, gomisin D was used as a quality marker of some traditional Chinese medicine (TCM) formulas. In this study, a rapid ultra-performance liquid chromatography/tandem mass spectrometry method (UPLC-MS/MS) was developed and validated to quantify gomisin D in rat plasma for a pharmacokinetic and bioavailability study. Acetonitrile was used to precipitate plasma proteins. Separations were performed on a BEH C18 column with a gradient mobile phase comprising of acetonitrile and water (0.1% formic acid). An electrospray ionization source was applied and operated in the positive ion mode. The multiple reaction monitoring mode (MRM) was utilized to quantify gomisin D and nomilin (internal standard, IS) using the transitions of m/z 531.2 → 383.1 and m/z 515.3 → 161.0, respectively. The calibration curve was linear over the working range from 1 to 4000 ng/mL ( = 0.993). The intra- and interday precision ranged from 1.9% to 12.9%. The extraction recovery of gomisin D was in the range of 79.2-86.3%. The validated UPLC-MS/MS method was then used to obtain the pharmacokinetic characteristics of gomisin D after intravenous (5 mg/kg) and intragastric (50 mg/kg) administration to rats. The bioavailability of gomisin D was 107.6%, indicating that this compound may become a promising intragastrical medication. Our results provided useful information for further preclinical studies on gomisin D.

Keywords: UPLC-MS/MS; bioavailability; gomisin D; pharmacokinetic.

MeSH terms

  • Animals
  • Biological Availability
  • Chromatography, High Pressure Liquid
  • Dioxoles / pharmacokinetics*
  • Dioxoles / pharmacology*
  • Lignans / pharmacokinetics*
  • Lignans / pharmacology*
  • Male
  • Plasma / metabolism*
  • Polycyclic Compounds / pharmacokinetics*
  • Polycyclic Compounds / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Tandem Mass Spectrometry

Substances

  • Dioxoles
  • Lignans
  • Polycyclic Compounds
  • gomisin D