Simultaneous Determination of Salidroside and Its Aglycone Metabolite <em>p</em>-Tyrosol in Rat Plasma by Liquid Chromatography-Tandem Mass Spectrometry

Abstract

Salidroside and its aglycone<em> p</em>-tyrosol are two major phenols in the genus <em>Rhodiola</em> and have been confirmed to possess various pharmacological properties. In our present study,<em> p</em>-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 <em>p</em>-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 (<em>m/z</em>) were 299.0→118.8 for salidroside, 137.0→118.9 for <em>p</em>-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 <em>p</em>-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.

Keywords

• salidroside
• &lt;em&gt;p&lt;/em&gt;-tyrosol
• metabolite
• LC-MS/MS
• pharmacokinetics