Development and Validation of an UPLC-Q-TOF-MS Method for Quantification of Fuziline in Beagle Dog After Intragastric and Intravenous Administration

J Chromatogr Sci. 2016 Mar;54(3):405-12. doi: 10.1093/chromsci/bmv156. Epub 2015 Nov 11.

Abstract

A specific and sensitive UPLC-Q-TOF-MS method operated in the positive ion mode was developed and validated for the quantification of Fuziline in Beagle dog plasma. Fuziline and Neoline internal standard were separated on an Acquity UPLC BEH C18 column with the total running time of 4 min using gradient elution at the flow rate of 0.25 mL/min. The calibration curves for Fuziline showed good linearity in the concentrations ranging from 2 to 400 ng/mL with correlation coefficients (r) greater than 0.9971. The lower limit of quantification was 0.8 ng/mL. Intra- and interbatch relative standard deviations ranged from 2.11 to 3.11% and 3.12 to 3.81%, respectively. Fuziline was stable under different sample storage and processing conditions. The developed method was successfully applied to the comparative pharmacokinetic study of Fuziline in Beagle dog after intravenous and oral administration. Low absolute bioavailability of Fuziline (1.45 ± 0.76%) suggested a significant metabolism transformation extent in Beagle dog.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aconitine / analogs & derivatives
  • Aconitine / blood
  • Administration, Intravenous
  • Administration, Oral
  • Alkaloids / blood
  • Alkaloids / pharmacokinetics*
  • Animals
  • Biological Availability
  • Calibration
  • Chromatography, High Pressure Liquid / methods*
  • Chromatography, High Pressure Liquid / standards
  • Dogs
  • Limit of Detection
  • Observer Variation
  • Reference Standards
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / methods*
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / standards
  • Terpenes / blood
  • Terpenes / pharmacokinetics*

Substances

  • Alkaloids
  • Terpenes
  • neoline
  • Aconitine