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The study was designed to establish an LC-MS/MS method for the simultaneous determination of scutellarin and its major metabolite isoscutellarin in rat tissues and plasma, and to investigate the effect of different route of administration on the tissue distribution of scutellarin and its metabolite in rats. Rats were treated both intravenously and intragastrically with 20 and 80 mg·kg-1 scutellarin, respectively. Blood and tissues were collected at predetermined intervals. The concentrations of scutellarin and isoscutellarin were determined by a validated LC-MS/MS method. The method was linear in concentration ranges of 10.0/5.00 - 5 000/2 500 ng·mL-1 for scutellarin/isoscutellarin in the rat plasma and 30.0/15.0 - 10 000/5 000 ng·g-1 in tissues with acceptable accuracy and precision. Data obtained after an intravenous administration of scutellarin to rats showed that the drug was distributed predominantly into the small intestine, bladder and kidney. The exposures of the metabolite isoscutellarin in plasma and tissue were both less than 5%of the parent drug. After an intragastric administration, stomach wall and small intestine were the preferred sites for scutellarin disposition, followed by bladder, adrenal gland and lung at concentrations significantly higher than its plasma concentration. The plasma exposure of isoscutellarin was higher than that of the parent drug, but its tissue exposure was significantly lower than that of scutellarin. The method established in this study was successfully applied to characterization of the tissue profiles of scutellarin and its metabolite in rats. The route of administration has a marked impact on the disposition of scutellarin and its metabolite in rats. Ratios of the tissue to plasma concentrations after intragastric administration were obviously higher than those after intravenous administration. Scutellarin could pass the blood-brain barrier in a marked extent, but isoscutellarin was not detected in the rat brain, which may be attributed to the fact that scutellarin is a higher-affinity substrate for OATP than isoscutellarin.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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