Simultaneous determination of salidroside and its aglycone metabolite p-tyrosol in rat plasma by liquid chromatography-tandem mass spectrometry

Molecules. 2012 Apr 23;17(4):4733-54. doi: 10.3390/molecules17044733.


Salidroside and its aglycone p-tyrosol are two major phenols in the genus Rhodiola and have been confirmed to possess various pharmacological properties. In our present study, p-tyrosol was identified as the deglycosylation metabolite of salidroside after intravenous (i.v.) administration to rats at a dose of 50 mg/kg, but was not detectable after intragastric gavage (i.g.) administration through HPLC-photodiode array detection (PDA) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis. Next, an accurate and precise LC-MS/MS method was developed to quantitatively determine salidroside and p-tyrosol in rat plasma samples. Samples were analyzed by LC-MS/MS on a reverse-phase xTerra MS C18 column which was equilibrated and eluted with an isocratic mixture of acetonitrile-water (1:9, v/v) at a flow rate of 0.3 mL/min. The analytes were monitored by multiple reaction monitoring (MRM) under the negative electrospray ionization mode. The precursor/product transitions (m/z) were 299.0 → 118.8 for salidroside, 137.0 → 118.9 for p-tyrosol and 150.1 → 106.9 for the internal standard (IS), paracetamol, respectively. The calibration curve was linear over the concentration ranges of 50-2,000 ng/mL for salidroside and 20-200 ng/mL for p-tyrosol. The inter- and intra-day accuracy and precision were within ± 15%. The method has been successfully applied to the pharmacokinetic study and the oral bioavailability was calculated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chromatography, Liquid*
  • Glucosides / blood*
  • Glucosides / chemistry
  • Glucosides / metabolism
  • Male
  • Phenols / blood*
  • Phenols / chemistry
  • Phenols / metabolism
  • Phenylethyl Alcohol / analogs & derivatives*
  • Phenylethyl Alcohol / blood
  • Phenylethyl Alcohol / chemistry
  • Rats
  • Rats, Wistar
  • Reproducibility of Results
  • Sensitivity and Specificity
  • Tandem Mass Spectrometry*


  • Glucosides
  • Phenols
  • 4-hydroxyphenylethanol
  • rhodioloside
  • Phenylethyl Alcohol