Identification of multiple constituents in the traditional Chinese medicine formula Zhi-zi-chi decoction and rat plasma after oral administration by liquid chromatography coupled to quadrupole time-of-flight tandem mass spectrometry

Rapid Commun Mass Spectrom. 2012 Oct 30;26(20):2443-53. doi: 10.1002/rcm.6360.


Rationale: Liquid chromatography (LC) coupled to positive electrospray ionization (ESI) tandem mass spectrometry (MS/MS) employing a time-of-flight tandem mass spectrometer was established to identify multi-components of Zhi-zi-chi decoction, a traditional Chinese medicine formula, and the constituents in rat plasma after oral administration of Zhi-zi-chi decoction.

Methods: The LC separation was achieved on a C(18) column. The mobile phase consisted of acetonitrile/0.2% formic acid with gradient program. The quadrupole time-of-flight (Q-TOF) mass spectrometer was operated in the positive ion mode with an electrospray ionization source (ESI+). The capillary voltage of the ion source was set at 4500 V and the capillary exit was 90 V. The nebulizer pressure was maintained at 1.2 bar. Hexapole radio frequencies 1 and 2 were set to 200 Vpp and 250 Vpp, respectively.

Results: A total 47 compounds in the Zhi-zi-chi decoction and 24 constituents in rat plasma after oral administration of Zhi-zi-chi decoction were identified. Of the 47 detected compounds in the Zhi-zi-chi decoction, 15 were identified by comparing the retention time and MS data with that of reference compounds and the rest were identified by MS analysis and retrieving the reference literature. Of the identified 24 compounds in rat plasma, 19 were the original form of the compounds absorbed from the 47 detected compounds, and the other five were the metabolites of the compounds existing in the Zhi-zi-chi decoction.

Conclusions: A fast and sensitive LC/Q-TOF MS method has been developed and successfully utilized to screen the active ingredients of a Chinese medical formula, Zhi-zi-chi decoction, for the first time. The results indicated that the 24 compounds identified in rat plasma were the potential active ingredients of Zhi-zi-chi decoction, which provided helpful chemical information for further pharmacology and active mechanism research on Zhi-zi-chi decoction and other traditional Chinese medicines.

MeSH terms

  • Administration, Oral
  • Animals
  • Carotenoids / analysis
  • Drugs, Chinese Herbal / administration & dosage
  • Drugs, Chinese Herbal / chemistry*
  • Drugs, Chinese Herbal / pharmacokinetics*
  • Iridoid Glucosides / analysis
  • Isoflavones / analysis
  • Male
  • Mass Spectrometry / economics
  • Mass Spectrometry / methods*
  • Monoterpenes / analysis
  • Plasma / metabolism
  • Rats
  • Rats, Wistar
  • Time Factors
  • Vitamin A / analogs & derivatives


  • Drugs, Chinese Herbal
  • Iridoid Glucosides
  • Isoflavones
  • Monoterpenes
  • trans-sodium crocetinate
  • Vitamin A
  • Carotenoids