Concurrent quantification and comparative pharmacokinetic analysis of bioactive compounds in the Herba Ephedrae-Semen Armeniacae Amarum herb pair

J Pharm Biomed Anal. 2015 May 10:109:67-73. doi: 10.1016/j.jpba.2015.02.004. Epub 2015 Feb 14.

Abstract

The Mahuang-Xingren herb-pair (MX), the combination of Herba Ephedrae (Mahuang in Chinese) and Semen Armeniacae Amarum (Xingren in Chinese), is a classical combination used in traditional Chinese Medicine to treat asthma and bronchitis. A simple and reliable ultra-performance liquid chromatography-tandem mass spectrometry method was developed to simultaneously quantify and compare the pharmacokinetics of 5 ephedra alkaloids and epimers of amygdalin and prunasin in rat plasma after oral administration of Mahuang, Xingren, and MX aqueous extracts. Samples were pretreated by a single-step protein precipitation with acetonitrile, and diphenhydramine hydrochloride and puerarin were used as internal standards. Pharmacokinetic parameters were investigated using DAS 3.2.2 (Mathematical Pharmacology Professional Committee of China, Shanghai, China). The validated method demonstrated adequate sensitivity, selectivity, and process efficiency for the bioanalysis of 8 compounds, including 3 pairs of epimers. MX administration improved the bioavailability of amygdalin and prunasin. Furthermore, MX facilitated intake of lower doses of ephedra alkaloids and increased elimination rates in comparison with Mahuang alone. These results illustrate the rationale behind the preferred use of the combination of Mahuang and Xingren. To our knowledge, this is the first report of stereo-selective metabolism of amygdalin. Further, the metabolic mechanism underlying this phenomenon merits future research attention.

Keywords: Amygdalin; Ephedrine; Epimers; LC–MS/MS; Pharmacokinetics; Xingren.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amygdalin / analysis
  • Amygdalin / pharmacokinetics
  • Animals
  • Asteraceae / chemistry*
  • Biological Availability
  • Chromatography, High Pressure Liquid
  • Drugs, Chinese Herbal / analysis*
  • Drugs, Chinese Herbal / pharmacokinetics*
  • Ephedra / chemistry*
  • Male
  • Nitriles / analysis
  • Nitriles / pharmacokinetics
  • Quality Control
  • Rats
  • Rats, Sprague-Dawley
  • Reference Standards
  • Reproducibility of Results
  • Stereoisomerism
  • Tandem Mass Spectrometry

Substances

  • Drugs, Chinese Herbal
  • Nitriles
  • prunasin
  • Amygdalin