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.
引文
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