大黄酸在小鼠体内的药代动力学及组织分布研究
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摘要
目的:建立测定小鼠血浆和组织中大黄酸含量的方法,并对其在小鼠体内的药代动力学和组织分布进行研究。方法:小鼠灌胃给予不同剂量(17. 25、34. 50、69. 00 mg/kg)的大黄酸后,采用固相萃取法预处理血浆和组织样品,并用高效液相色谱-荧光检测器(HPLC-FLD)检测各时间点血浆和组织器官药物浓度。采用Venusil XBP C18(L)(250 mm×4. 6 mm,5μm)色谱柱,柱温:30℃;以甲醇-0. 1%磷酸水(70∶30)为流动相,体积流量:1 ml/min;荧光检测器的激发波长435 nm,发射波长515 nm。结果:大黄酸血浆及各组织样品在0. 0095~19. 52μg/ml浓度范围内呈良好的线性关系;提取回收率在86. 4~96. 8%。大黄酸在小鼠组织中的分布情况为:肝>胃>肠>肺>脾>肾>心>脂肪>脑>肌肉。结论:本方法简便快捷,灵敏准确,可用于大黄酸体内过程的研究。
Aim: To establish a method for the quantitative analysis of rhein in plasma and tissues of mice and the pharmacokinetics and tissue distribution of rhein was studied. Methods: The plasma and tissue samples of mice were pretreated with solid phase extraction after intragastric administration different doses(17. 25,34. 50,17. 25 mg/kg) of rhein and the concentration of rhein in plasma and tissue at each point was detected by HPLC-FLD. Separation was carried on Venusil XBP C18(L) column(250 mm × 4. 6 mm,5 μm) with the column temperature was 30℃ and the mobile phase was consisted of methanol-0. 1% phosphoric acid in water(70: 30) at a flow rate of 1. 0 ml/min. HPLC-FLD was performed at excitation wavelength 435 nm and emission wavelength 515 nm for rhein and internal standard. Results: Good linearity was obtained in plasma and tissue samples in the range of 0. 0095-19. 52 μg/ml,while the extraction recoveries were 86. 4%-96. 8%. The distribution of rhein in the tissue of mice was as follows: Stomach > liver > intestine > lung > kidney > spleen > heart > brain > fat > muscle. Conclusion: A simple,sensitive and accurate method was developed and can be applied to the investigation of process in vivo of rhein.
Aim: To establish a method for the quantitative analysis of rhein in plasma and tissues of mice and the pharmacokinetics and tissue distribution of rhein was studied. Methods: The plasma and tissue samples of mice were pretreated with solid phase extraction after intragastric administration different doses(17. 25,34. 50,17. 25 mg/kg) of rhein and the concentration of rhein in plasma and tissue at each point was detected by HPLC-FLD. Separation was carried on Venusil XBP C18(L) column(250 mm × 4. 6 mm,5 μm) with the column temperature was 30℃ and the mobile phase was consisted of methanol-0. 1% phosphoric acid in water(70: 30) at a flow rate of 1. 0 ml/min. HPLC-FLD was performed at excitation wavelength 435 nm and emission wavelength 515 nm for rhein and internal standard. Results: Good linearity was obtained in plasma and tissue samples in the range of 0. 0095-19. 52 μg/ml,while the extraction recoveries were 86. 4%-96. 8%. The distribution of rhein in the tissue of mice was as follows: Stomach > liver > intestine > lung > kidney > spleen > heart > brain > fat > muscle. Conclusion: A simple,sensitive and accurate method was developed and can be applied to the investigation of process in vivo of rhein.
引文
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2 Shi P,Huang Z,Chen G. Rhein induces apoptosis and cell cycle arrest in human hepatocellular carcinoma BEL-7402 cells. Am J Chin Med,2008;36 (4)∶805~813
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7 许乾丽,茅向军,宋晓宁. HPLC法同时测定六味安消胶囊中芦荟大黄素、大黄酸、大黄素、大黄酚和大黄素甲醚的含量.药物分析杂志,2010; 30(10)∶1841~1844
8 万萍,孙建国,郝刚,等.大黄酸的HPLC-荧光检测及其在人体药代动力学中的应用.中国药科大学学报,2013; 44(1)∶73~76
9 张锦雯,王广基,孙建国,等. HPLC-荧光检测法测定大鼠血浆中大黄酸的浓度及其药代动力学.中国天然药物,2005; 3(4)∶238~240
10 韩媛媛,王利勇,杜光玲,等. HPLC-荧光检测法测定东乐膏中大黄酸、大黄素、大黄酚的含量.药物分析杂志,2010; 30(6)∶1016~1018
11 Jiang C Q,He J X. Simultaneous determination of Aloe-emodin and Rhein by synchronous fluorescence spectroscopy. J Pharm Biomed Anal,2002; 29∶737~742
2 Shi P,Huang Z,Chen G. Rhein induces apoptosis and cell cycle arrest in human hepatocellular carcinoma BEL-7402 cells. Am J Chin Med,2008;36 (4)∶805~813
3 周柳如,彭青.四种中药单体对耐甲氧西林金黄色葡萄球菌的体外抗菌作用研究.现代医院,2011; 11(6)∶34~35
4 郭啸华,刘志红,彭艾,等.大黄酸对2型糖尿病大鼠疗效观察.中华肾脏病杂志,2002; 18(4)∶280~284
5 万晓强,郑紫丹,尚军洁,等.大黄酸对免疫性肝纤维化大鼠形成的影响.重庆医学,2009; 38(10)∶1204~1206
6 黄良永,张春丽,路丽. HPLC法同时测定利胆排毒口服液中大黄酸、大黄素、大黄酚的含量.中国药师,2012; 15(8)∶1122~1124
7 许乾丽,茅向军,宋晓宁. HPLC法同时测定六味安消胶囊中芦荟大黄素、大黄酸、大黄素、大黄酚和大黄素甲醚的含量.药物分析杂志,2010; 30(10)∶1841~1844
8 万萍,孙建国,郝刚,等.大黄酸的HPLC-荧光检测及其在人体药代动力学中的应用.中国药科大学学报,2013; 44(1)∶73~76
9 张锦雯,王广基,孙建国,等. HPLC-荧光检测法测定大鼠血浆中大黄酸的浓度及其药代动力学.中国天然药物,2005; 3(4)∶238~240
10 韩媛媛,王利勇,杜光玲,等. HPLC-荧光检测法测定东乐膏中大黄酸、大黄素、大黄酚的含量.药物分析杂志,2010; 30(6)∶1016~1018
11 Jiang C Q,He J X. Simultaneous determination of Aloe-emodin and Rhein by synchronous fluorescence spectroscopy. J Pharm Biomed Anal,2002; 29∶737~742