中国中药杂志

2018, v.43(18) 3748-3755

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基于UPLC-MS/MS分析胃溃疡模型大鼠口服加味小柴胡颗粒后血浆中8种有效成分的药代动力学
Pharmacokinetics of eight constituents in rat plasma after oral administration of Modified Xiaochaihu Granules for gastric ulcer based on UPLC-MS/MS

杨梦玲;尤朋涛;何丽珊;陈树和;周爱军;刘焱文;陈新;
YANG Meng-ling;YOU Peng-tao;HE Li-shan;CHEN Shu-he;ZHOU Ai-jun;LIU Yan-wen;CHEN Xin;Hubei Provincial Key Laboratory for Resource and Chemistry of Chinese Medicine,Hubei University of Chinese Medicine;Wuhan Institute for Food and Cometic Control;Hubei Provincial Hospital of Traditional Chinese Medicine;Dongguan Hospital of Traditional Chinese Medicine;

摘要(Abstract):

该文建立高效液相色谱-质谱法(UPLC-MS/MS)测定胃溃疡模型大鼠血浆中8个有效成分(黄芩苷、汉黄芩苷、黄芩素、甘草苷、甘草酸、盐酸小檗碱、柴胡皂苷a、柴胡皂苷d)含量的方法,用于加味小柴胡颗粒的药代动力学研究。采用Zorbax SB-C18色谱柱(2.1 mm×100 mm,1.8μm),流动相为乙腈-0.1%甲酸水溶液,梯度洗脱,流速0.4 m L·min-1,柱温40℃,ESI离子源,MRM检测模式。结果各成分的线性关系良好(r>0.996);日间和日内精密度RSD均<15%;各成分的提取回收率在81.92%~104.8%。8种成分的达峰时间(tmax)依次为(2.69±2.02),(5.17±2.04),(0.25±0),(0.83±0.26),(0.92±0.20),(0.92±0.20),(0.58±0.20),(0.083±0)h,半衰期(t1/2)依次为(7.85±0.34),(10.16±2.21),(6.79±0.21),(8.32±0.48),(11.05±1.78),(11.56±3.46),(15.30±1.84),(5.54±1.91)h,药峰浓度(Cmax)依次为(55.02±1.67),(213.66±4.62),(62.61±0.69),(68.43±1.42),(62.22±0.39),(30.17±1.89),(61.79±4.81),(38.02±1.75)μg·L-1。该方法简便、准确、重复性好、专属性强,为加味小柴胡颗粒治疗胃溃疡的临床用药提供了实验依据。
An ultra-performance liquid chromatography-tandem mass spectrometric method( UPLC-MS/MS) was developed in this study to simultaneously determine the contents of eight effective constituents in rat plasma,including baicalin,wogonoside,baicalein,liquiritin,glycyrrhizic acid,berberine hydrochloride,saikosaponin a and saikosaponin d in plasma of gastric ulcer rats,and investigate the pharmacokinetics of Modified Xiaochaihu Granules. Chromatographic separation was conducted on Zorbax SB-C18 column( 2. 1 mm × 100 mm,1. 8 μm) with acetonitrile-0. 1% formic acid aqueous solution as the mobile phase for gradient elution,at a flow rate of 0. 4 m L·min-1 and column temperature of 40 ℃. Detection was performed in the multiple reaction monitoring( MRM) mode with ESI ion source. All calibration curves showed good linearity( r > 0. 996) over a wide concentration range for all constituents.RSDs of intra-day and inter-day precision were all within 15% and the extraction recoveries of all the constituents were in the range of81. 92% to 104. 8%. The time to peak( tmax) of these eight constituents was( 2. 69 ± 2. 02),( 5. 17 ± 2. 04),( 0. 25 ± 0),( 0. 83 ±0. 26),( 0. 92 ± 0. 20),( 0. 92 ± 0. 20),( 0. 58 ± 0. 20),and( 0. 083 ± 0) h,respectively; the half-life( t1/2) of them was( 7. 85 ± 0. 34),( 10. 16 ± 2. 21),( 6. 79 ± 0. 21),( 8. 32 ± 0. 48),( 11. 05 ± 1. 78),( 11. 56 ± 3. 46),( 15. 30 ± 1. 84),and( 5. 54 ± 1. 91) h,respectively; the peak concentration( Cmax) of them was( 55. 02 ± 1. 67),( 213. 66 ± 4. 62),( 62. 61 ± 0. 69),( 68. 43 ± 1. 42),( 62. 22 ± 0. 39),( 30. 17 ± 1. 89),( 61. 79 ± 4. 81),and( 38. 02 ± 1. 75) μg·L-1,respectively. This established method is simple and accurate with good repeatability and strong specificity,which could provide modern experimental basis for modified Xiaochaihu granules in clinical treatment of gastric ulcer.

关键词(KeyWords): 加味小柴胡颗粒;胃溃疡;药代动力学
Modified Xiaochaihu Granules;gastric ulcer;pharmacokinetics

Abstract:

Keywords:

基金项目(Foundation): 广东省东莞市科技局项目(东科[2014]130);; 湖北中医药大学科研启动基金项目(5114-100714)

作者(Author): 杨梦玲;尤朋涛;何丽珊;陈树和;周爱军;刘焱文;陈新;
YANG Meng-ling;YOU Peng-tao;HE Li-shan;CHEN Shu-he;ZHOU Ai-jun;LIU Yan-wen;CHEN Xin;Hubei Provincial Key Laboratory for Resource and Chemistry of Chinese Medicine,Hubei University of Chinese Medicine;Wuhan Institute for Food and Cometic Control;Hubei Provincial Hospital of Traditional Chinese Medicine;Dongguan Hospital of Traditional Chinese Medicine;

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DOI: 10.19540/j.cnki.cjcmm.2018.0104

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