Study on the stereoselective excretion of tetrahydropalmatine enantiomers in rats and identification of in vivo metabolites by liquid chromatography-tandem mass spectrometry

Chirality. 2010 Mar;22(3):355-60. doi: 10.1002/chir.20750.


The objective of this work was to study the stereoselectivity in excretion of tetrahydropalmatine (THP) enantiomers by rats and identify the metabolites of racemic THP (rac-THP) in rat urine. Urine and bile samples were collected at various time intervals after a single oral dose of rac-THP. The concentrations of THP enantiomers in rat urine and bile were determined using a modification of an achiral-chiral high-performance liquid chromatographic (HPLC) method that had been previously published. The cumulative urinary excretion over 96 h of (-)-THP and (+)-THP was found to be 55.49 +/- 36.9 microg and 18.33 +/- 9.7 microg, respectively. The cumulative biliary excretion over 24 h of (-)-THP and (+)-THP was 19.19 +/- 14.6 microg and 12.53 +/- 10.4 microg, respectively. The enantiomeric (-/+) concentration ratios of THP changed from 2.80 to 5.15 in urine, and from 1.36 to 1.80 in bile. The mean cumulative amount of (-)-THP was significantly higher than that of (+)-THP both in urine and bile samples. However, the enantiomeric (-/+) concentration ratios in rat urine and bile were significantly lower than those ratios in rat plasma. These findings suggested the excretion of THP enantiomers was stereoselective rather than a reflection of chiral pharmacokinetic aspects in plasma and (-)-THP was preferentially excreted in rat urine and bile. Three O-demethylation metabolites and the parent drug rac-THP were detected by liquid chromatography-tandem mass spectrometry in rat urine. One metabolite was obtained by preparative HPLC and identified as 10-O-demethyl-THP.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Berberine Alkaloids / urine*
  • Bile / chemistry*
  • Chromatography, High Pressure Liquid / methods
  • Drugs, Chinese Herbal / chemistry*
  • Mass Spectrometry / methods*
  • Rats
  • Rats, Sprague-Dawley
  • Stereoisomerism


  • Berberine Alkaloids
  • Drugs, Chinese Herbal
  • tetrahydropalmatine