| Salidroside and its metabolite p-tyrosol are two major phenols in Genus Rhodiola and have been confirmed possessing various pharmacological properties including resisting anoxia, anti-fatiguing, anti-aging, anti-cancer, anti-inflammation, antioxidative, hepatoprotective and cardioprotective effects and was used to the prophylaxis and therapeutics of many diseases.The method of LC/PDA and LC-MS/MS was used to indentify the metabolism of salidroside in rat plasma. Salidroside and its deglycosylation metabolite p-tyrosol were detected in rat plasma after intravenous (i.v.) administration at a dose of50mg·kg-1, but p-tyrosol was not detectable after intragastric gavage (i.g.) administration at a dose of100mg·kg-1An LC-MS/MS method was developed to quantitatively determine salidroside and p-tyrosol in rat plasma, tissue, feces, urine and bile samples. Samples were analyzed by LC-MS/MS on a reverse-phase xTerra MS C18column which was equilibrated and eluted with an isocratic mixture of acetonitrile-water (1:9, v/v) at a flow rate of0.3mL·min-1. The analytes were monitored by multiple reaction monitoring (MRM) under the negative electrospray ionization mode. The precursor/product transitions (m/z) were299.0→118.8for salidroside,137.0→118.9for p-tyrosol and150.1→106.9for the internal standard (IS), paracetamol, respectively. The method was simple, quickly, accurate and precise, selectivity enough and has been successfully applied to the pharmacokinetic study.The pharmacokinetic study of salidroside and its metabolite p-tyrosol in rat plasma was investigated after after intravenous (i.v.) administration at a dose of50mg·kg-1According to the mean concentration-time profile and pharmacokinetic parameters of salidroside and p-tyrosol in rat plasma, the clearance of salidroside was very quick and almost cleared all at4h after i.v. administration, and p-tyrosol got the lowest value at the same time although the clearance was slower. The total amount of p-tyrosol was only2%of salidroside according to the estimation of AUC. Salidroside was detected only, and the value was maximm at about0.5h after i.g. administration. The results showed that biological availability of salidroside was51.97%only.The tissue distribution regularition of salidroside and p-tyrosol was investigated after i.v. administration at a dose of50mg·kg-1, the results indicated that the content of salidroside in liver was significantly higher than others, and the contents of kidney and heart tissue was followed, Whereas data were not meaningful to spleen, lung and brain because the concentration levels of salidroside were below LLOQ. A significant amount of p-tyrosol was detected in heart, followed by spleen and kidney (No significant difference between them), liver, lungs and brain were fllowed. The clearance of salidroside and p-tyrosol in tissues were very high, and there was none response4h after i.v. administration.The accumulation of salidroside and its metabolite p-tyrosol in excretion pathway was investigated after after intravenous (i.v.) administration at a dose of50mg-kg'1. The results indicated that salidroside was excretion by urine mostly. The cumulative contents of salidroside in feces, urine and bile samples were0.30±0.01%,64.00±4.15%and2.87±0.04%dose of administration, respectly. And the cumulative contents of p-tyrosol in feces, urine and bile samples were1.48±0.04%,0.19±0.01%and0.02±0.00%dose of administration, respectly. From this, kidney was the most important excretion organ for salidroside.A pharmacokinetic study of salidroside and its metabolite p-tyrosol in rats were investigated, and the absorpation, distribution, metabolism, excretion of salidroside was clarified, in order to provide a theories basis for the clinical medication, reasonable development and application of salidroside.
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