Bioavailability and Pharmacokinetics of Anisatin in Mouse Blood by Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry

Biomed Res Int. 2020 Dec 23:2020:8835447. doi: 10.1155/2020/8835447. eCollection 2020.

Abstract

Background: Anisatin is a neurotoxic sesquiterpene dilactone wildly found in plants of the family Illiciaceae. Due to morphological similarities among Illiciaceae fruits, fatal poisonings are frequent.

Objective: This study is aimed at developing a rapid, simple ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method to determine anisatin's bioavailability in mouse blood and the method's application to pharmacokinetics.

Methods: Blood samples were preprocessed by protein precipitation using acetonitrile. Salicin (internal standard, IS) and anisatin were gradient-eluted by a mobile phase of methanol and water (0.1% formic acid) in a UPLC BEH C18 column. This step involved using an electrospray ionization source of anisatin at a mass-to-charge ratio (m/z) of 327.1 → 127.0 and IS at m/z 285.1 → 122.9 in the negative ion mode with multiple reaction monitoring.

Results: The calibration curve ranged from 1 to 2000 ng/ml (r > 0.995), with the method's accuracy ranging from 86.3% to 106.9%. Intraday and interday precision were lower than 14%, and the matrix effect was between 93.9% and 103.3%. The recovery rate was higher than 67.2%.

Conclusions: The developed UPLC-MS/MS method was successfully used for a pharmacokinetic study of oral (1 mg/kg) and intravenous (0.5 mg/kg) administration of anisatin to mice-the absolute bioavailability of anisatin in the mouse blood was 22.6%.

MeSH terms

  • Animals
  • Biological Availability
  • Chromatography, High Pressure Liquid / methods*
  • Lactones / blood*
  • Lactones / chemistry
  • Lactones / pharmacokinetics*
  • Linear Models
  • Male
  • Mice
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Sesquiterpenes / blood*
  • Sesquiterpenes / chemistry
  • Sesquiterpenes / pharmacokinetics*
  • Spiro Compounds / blood*
  • Spiro Compounds / chemistry
  • Spiro Compounds / pharmacokinetics*
  • Tandem Mass Spectrometry / methods*

Substances

  • Lactones
  • Sesquiterpenes
  • Spiro Compounds
  • anisatin