Metabolism of dl-praeruptorin a in rat liver microsomes using HPLC-electrospray ionization tandem mass spectrometry

  • Hang Ruan
  • Zhen Zhang
  • Xin-fang Liang
  • Yan Fu
  • Mei-qin Su
  • Qi-lin Liu
  • Xiu-min Wang
  • Xuan Zhu
Research Articles Drug Actions

Abstract

dl-Praeruptorin A (Pd-Ia) is the major active constituent of the traditional Chinese medicine Peucedanum praeruptorum Dunn. Recently it has been identified as a novel agent in the treatment and prevention of cardiovascular diseases. Accordingly, we investigated the metabolism of Pd-Ia in rat liver microsomes. The involvement of cytochrome P450 (CYP) and CYP isoforms were identified using a CYP-specific inhibitor (SKF-525A), CYP-selective inhibitors (α-naphthoflavone, metyrapone, fluvastatin, quinidine, disulfiram, ketoconazole and ticlopidine) and CYP-selective inducers (phenobarbital, dexamethasone and β-naphthoflavone). Residual concentrations of the substrate and metabolites were determined by HPLC, and further identified by their mass spectra and chromatographic behavior. These experiments showed that CYP450 is involved in Pd-Ia metabolism, and that the major CYP isoform responsible is CYP3A1/2, which acts in a concentration-dependent manner. Four Pd-Ia metabolites (M1, M2, M3, and M4) were detected after incubation with rat liver microsomes. Hydroxylation was the primary metabolic pathway of Pd-Ia, and possible chemical structures of the metabolites were identified. Further research is now needed to link the metabolism of Pd-Ia to its drug-drug interactions.

Key words

dl-Praeruptorin A Cytochrome P450 isoforms Metabolites Rat liver microsomes In vitro HPLC-ESI-MSn 

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Copyright information

© The Pharmaceutical Society of Korea and Springer Netherlands 2011

Authors and Affiliations

  • Hang Ruan
    • 1
  • Zhen Zhang
    • 1
  • Xin-fang Liang
    • 2
  • Yan Fu
    • 2
  • Mei-qin Su
    • 2
  • Qi-lin Liu
    • 2
  • Xiu-min Wang
    • 2
  • Xuan Zhu
    • 2
  1. 1.College of MedicalXiamen UniversityXiamenChina
  2. 2.College of Pharmaceutical ScienceXiamen UniversityXiamenChina

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