金钗石斛在SD大鼠体内的药代动力学研究
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摘要
目的通过UPLC-MS方法检测大鼠血浆中石斛碱的含量,探讨金钗石斛细粉灌胃给药后在大鼠体内药代动力学的特征。方法建立血浆样品中石斛碱的分析方法,大鼠经灌胃给予金钗石斛细粉0.8 g/kg,分别于0、2、6、10、15、20、30、40、60、90、120、180、240、480、720、1 440 min收集大鼠血浆,样品处理后采用Thermo Q Exactive四极杆-静电场轨道阱高分辨质谱系统分析,Hypersil Gold C18色谱柱(150 mm×2.1 mm,1.9μm),以0.1%甲酸水溶液-乙腈梯度洗脱,体积流量0.3m L/min,ESI源正离子检测石斛碱含量,盐酸伪麻黄碱为内标。结果大鼠血浆样品中内源性物质对石斛碱含量测定无干扰,方法学考察符合要求,所建立的分析方法能够满足临床前药代动力学的研究。药动学结果显示,给药后血浆中石斛碱浓度平均达峰时间为11.71 min,最大血药浓度平均值为212.17μg/L,平均半衰期为351.95 min。结论以石斛碱为检测指标,研究了金钗石斛细粉灌胃给药后在大鼠体内药代动力学的特征,为其进一步的研究与开发提供了参考。
Objective To establish UPLC-MS analysis method for the determination of dendrobine in plasma of rats,and explore pharmacokinetics characteristics of Dendrobium nobile Lindl. Methods In 0,2,6,10,15,20,30,40,60,90,120,180,240,480,720,1 440 min after gavage,plasma were collected and precipitated by acetonitrile,and the supernatant was detected with UPLC-MS. The chromatography separation was performed on a Thermo Hypersil Gold C18 column( 150 mm × 2. 1 mm,1. 9 μm) with acetonitrile-0. 1% formic acid in water by gradient elution. Electrospray ionization( ESI) source was applied and operated in positive ion mode. Meanwhile,pseudoephedrine hydrochloride was used as the internal standard for determining the concentration. Results The results of the method validation tests showed that endogenous substances had no interference with the assay of dendrobine,and the methodological study met the requirements. Dendrobine was detected in the plasma after 2 min,and the peak of plasma concentration was shown at 11. 71 min after gavage. As the results,Cmaxand t1/2 were212. 17 μg/L and 351. 95 min,respectively. Conclusion The pharmacokinetics characteristics of D. nobile would provide a reference for further research and development.
Objective To establish UPLC-MS analysis method for the determination of dendrobine in plasma of rats,and explore pharmacokinetics characteristics of Dendrobium nobile Lindl. Methods In 0,2,6,10,15,20,30,40,60,90,120,180,240,480,720,1 440 min after gavage,plasma were collected and precipitated by acetonitrile,and the supernatant was detected with UPLC-MS. The chromatography separation was performed on a Thermo Hypersil Gold C18 column( 150 mm × 2. 1 mm,1. 9 μm) with acetonitrile-0. 1% formic acid in water by gradient elution. Electrospray ionization( ESI) source was applied and operated in positive ion mode. Meanwhile,pseudoephedrine hydrochloride was used as the internal standard for determining the concentration. Results The results of the method validation tests showed that endogenous substances had no interference with the assay of dendrobine,and the methodological study met the requirements. Dendrobine was detected in the plasma after 2 min,and the peak of plasma concentration was shown at 11. 71 min after gavage. As the results,Cmaxand t1/2 were212. 17 μg/L and 351. 95 min,respectively. Conclusion The pharmacokinetics characteristics of D. nobile would provide a reference for further research and development.
引文
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[2]陶凤,金徽,杨贵忠,等.金钗石斛水提物对糖尿病大鼠肾组织非酶糖基化及氧化的影响[J].山东大学学报:医学版,2012,50(10):11-15.
[3]刘名昆,李国庆.石斛提取物抗肿瘤作用研究进展[J].现代医药卫生,2015,31(23):3571-3574.
[4]宾捷,胡余明,尹进,等.金钗石斛对老龄小鼠抗氧化作用的实验研究[J].实用预防医学,2010,17(6):1063-1064.
[5]张明辉,李菲,张玮,等.金钗石斛总生物碱对Aβ25-35所致大鼠海马组织Aβ含量的影响[J].遵义医学院学报,2016,39(1):18-21.
[6]Li L S,Lu Y L,Nie J,et al.Dendrobium nobile lindl Alkaloid,a novel autophagy inducer,protects against axonal degeneration induced by Aβ25-35 in hippocampus neurons in vitro[J].CNS Neurosci Ther,2017,23(4):329-340.
[7]Yang S,Gong Q H,Wu Q,et al.Alkaloids enriched extract from Dendrobium nobile Lindl.attenuates tau protein hyperphosphorylation and apoptosis induced by lipopolysaccharide in rat brain[J].Phytomedicine,2014,21(5):712-716.
[8]白金丽,温淑湘.金钗石斛提取物抗白内障的体外实验研究[J].云南中医中药杂志,2009,30(9):57-59.
[9]王亚芸,任建武.石斛碱的研究进展[J].山东农业大学学报:自然科学版,2015,46(1):152-158.
[10]Xu J,Han Q B,Li S L,et al.Chemistry,bioactivity and quality control of Dendrobium,a commonly used tonic herb in traditional Chinese medicine[J].Phytochem Rev,2013,12(2):341-367.
[11]张晓敏,孙志蓉,陈龙,等.金钗石斛的化学成分和药理作用研究进展[J].中国现代应用药学,2014,31(7):895-899.
[12]汪代芳,侴桂新,赵宁毅,等.金钗石斛茎的化学成分研究[J].中草药,2012,43(8):1492-1495.
[13]Nie J,Tian Y,Zhang Y,et al.Dendrobium alkaloids prevent Aβ25-35-induced neuronal and synaptic loss via promoting neurotrophic factors expression in mice[J].Peer J,2016,4(5594):e2739.
[14]鲁艳柳,黄思,汪敏,等.UPLC/LTQ-Orbitrap-MS技术鉴定石斛碱在人肝微粒体中的代谢产物[J].中国实验方剂学杂志,2018,24(4):72-77.
[15]国家药典委员会.中华人民共和国药典[S].北京:中国医药科技出版社,2015:92-93.
[16]何芋岐,鲁艳柳,李利生,等.基于UPLC-ESI-Orbitrap-MS技术对金钗石斛生物碱的分析[J].中国实验方剂学杂志,2017,23(20):30-35.