Pharmacokinetics and metabolism study of veratramine in mice after oral administration using LC-MS/MS

Biomed Chromatogr. 2016 Sep;30(9):1515-22. doi: 10.1002/bmc.3717. Epub 2016 Apr 3.

Abstract

A simple and sensitive high-performance liquid chromatography coupled with hybrid triple quadrupole-linear ion trap mass spectrometry (Q-trap-MS) method was developed and validated for the determination of veratramine, the major bioactive and neurotoxic component in Veratrum nigrum L. Veratramine and the internal standard (IS) were separated with a Waters Symmetry C18 column and eluted with a gradient mobile phase system containing acetonitrile and 0.1% aqueous formic acid. The analysis was performed by using positive electrospray ionization mode with multiple reaction monitoring (MRM). Transition ions of m/z 410.2 → 295.2 for veratramine and m/z 426.1 → 113.8 for the IS were monitored. The method was validated with a good linearity in the range of 1-1000 ng/mL and lower limit of quantification of 1 ng/mL. The precision (CV) of intra- and inter-day ranged from 3.92 to 7.29%, while the accuracy (bias) intra- and inter-day were between -4.78 and 1.65%. The recovery, stability and matrix effect were within the acceptable ranges. Five metabolites of veratramine, including four hydroxylated and one sulfated metabolites, were tentatively identified using predictive MRM-information dependent acquisition-enhanced product ion mode (predictive MRM-IDA-EPI). The developed method was successfully applied to the pharmacokinetic and metabolic study of veratramine in mice after oral administration of veratramine. Copyright © 2016 John Wiley & Sons, Ltd.

Keywords: Veratrum nigrum; metabolism; mouse; pharmacokinetics; veratramine.

Publication types

  • Validation Study

MeSH terms

  • Administration, Oral
  • Animals
  • Chromatography, Liquid / methods*
  • Limit of Detection
  • Mice
  • Reference Standards
  • Tandem Mass Spectrometry / methods*
  • Veratrum Alkaloids / administration & dosage
  • Veratrum Alkaloids / pharmacokinetics*

Substances

  • Veratrum Alkaloids
  • veratramine