Abstract
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.
Highlights
Plant phenols often occur as glycosides, such as flavonoid glycosides, and phenylethanoid glycosides
The content of salidroside is one of the criteria to evaluate the medicinal quality of Rhodiola [13], as well as being one of active standard components for Rhodiola rosea extract, which is valued as a strengthening tonic to increase physical and mental stamina and sold under different brand names on major websites and in drug stores (Walgreens and GNC) in the United States. p-Tyrosol is the most abundant biophenol in extra virgin olive oil [14]
The analysis methods of salidroside have been developed and applied to plant materials and biological matrices, including liquid chromatography with ultraviolet detection (LC-UV) [18], liquid chromatography with mass spectrometry (LC-MS) [17,19], and liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) [13,22], and the simultaneous determination of salidroside and p-tyrosol in Rhodiola were established by HPLC [23,24]
Summary
Plant phenols often occur as glycosides, such as flavonoid glycosides, and phenylethanoid glycosides. The analysis methods of salidroside have been developed and applied to plant materials and biological matrices, including liquid chromatography with ultraviolet detection (LC-UV) [18], liquid chromatography with mass spectrometry (LC-MS) [17,19], and liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) [13,22], and the simultaneous determination of salidroside and p-tyrosol in Rhodiola were established by HPLC [23,24] In all these studies the metabolic characteristics of salidroside in vivo has not been mentioned so far. The pharmacokinetic studies of salidroside in rats after i.g. and i.v. administration were carried out afterwards
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