Pharmacokinetics and biotransformation investigation in beagle dog of active compounds from naoxintong capsule

Biomed Pharmacother. 2021 Jan:133:110940. doi: 10.1016/j.biopha.2020.110940. Epub 2020 Nov 20.

Abstract

Naoxintong Capsule (NXTC), a standardized herbal medicine, has been widely applied in treating cardiovascular and cerebrovascular diseases with remarkable efficacy. However, the efficacy contributing components of NXTC are unclear, and the in vivo absorption and metabolism processes of NXTC remain largely obscured. In this study, using beagle dog as model species, we have identified and tentatively characterized 25 prototype and 15 catabolites of NXTC in beagle dog plasma by ultra-fast liquid chromatography/quadrupole-time-of-flight tandem mass spectrometry (UFLC-Q-TOF-MS/MS). We have proposed the in vivo bio-transformation pathways of these absorbed constituents. In addition, for six crucial components, we have developed a quantitative method and conducted plasma pharmacokinetic study of these six components by rapid resolution liquid chromatography tandem triple quadrupole mass spectrometry (RRLC-QQQ-MS/MS). In conclude, our study provided comprehensive insights into the understanding of the plasma absorbed components profiling of NXTC as well as their in vivo transformation behaviors, which would be of great value for identifying efficacy contributing critical components as well as mechanism related investigations of NXTC in the future.

Keywords: LC–MS/MS; Naoxintong capsule; Pharmacokinetics; Plasma metabolite; UFLC-Q-TOF-MS/MS.

MeSH terms

  • Administration, Oral
  • Animals
  • Biotransformation
  • Capsules
  • Chromatography, High Pressure Liquid
  • Dogs
  • Drugs, Chinese Herbal / administration & dosage
  • Drugs, Chinese Herbal / pharmacokinetics*
  • Female
  • Male
  • Spectrometry, Mass, Electrospray Ionization
  • Tandem Mass Spectrometry

Substances

  • Capsules
  • Drugs, Chinese Herbal
  • naoxintong