半枝莲提取物中半枝莲碱A和半枝莲碱B大鼠体内药代动力学研究

目的?建立同时测定生物样品中半枝莲碱A和半枝莲碱B的LC-MS/MS分析方法，并对其药代动力学进行研究。方法?血浆样品采用乙酸乙酯萃取，BDS Hypersil C₁₈(50mm×2.1mm， 2.4μm)色谱柱进行梯度洗脱，柱温40℃，流动相为乙腈:0.05％甲酸水溶液，流速为0.25mL/min。电喷雾离子源，MRM模式。大鼠单剂量灌胃500mg/kg半枝莲提取物后，检测半枝莲碱A和半枝莲碱B的血药浓度，DAS软件对其血药浓度-时间曲线进行拟合，统计矩模型计算药动学参数。结果?半枝莲碱A和半枝莲碱B在0.512~258.0ng/mL和0.482~241.0ng/mL间线性关系良好（r2>0.994）；精密度、准确度、提取回收率和基质效应、稳定性均符合生物样品分析要求。半枝莲碱A和半枝莲碱B的AUC_(0-t)分别为(88.69±12.4)μg/L·h和(57.09±9.84)μg/L·h，达峰浓度分别为(10.22±1.31)ng/mL和(6.27±0.80)ng/mL。结论?该方法简便、准确、灵敏，可用于半枝莲提取物中半枝莲碱A和半枝莲碱B体内药代动力学研究。 

Pharmacokinetic Study of Scutebarbatine A and Scutebarbatine B in Rats After Orally Administration of Scutellaria Barbata Extract Using a LC-MS/MS Method

OBJECTIVE?The aim of this study was to develop and validate a LC-MS/MS method to simultaneously determination of Scutebarbatine A and Scutebarbatine B in rat plasma and applicated this method to pharmacokinetic study of Scutebarbatine A and Scutebarbatine B after oral administration of Scutellaria barbata extract. METHODS?Plasma samples were prepared with ethyl acetate using liquid-liquid extraction. Then samples were separated by using BDS Hypersil C₁₈(50mm×2.1mm， 2.4μm) with gradient elution program and oven temperature was set at 40℃. And the mobile phase was consisted with acetonitrile/water (0.05% formic acid) at a flow rate of 0.25mL/min. Determination was carried out on a tandem mass spectrometer in positive ion mode using a multiple reaction monitoring (MRM) via a electrospray ionization (ESI) interface. After oral administration of 500mg/kg Scutellaria barbata extract， plasma samples were collected and analyzed by using a DAS software to analyze to the pharmacokinetic parameters. RESULTS?Scutebarbatine A and Scutebarbatine B were liner at the range of 0.512~258.0ng/mL， 0.482~241.0ng/mL， respectively with a r2 larger than 0.994. Accuracy， precious， extraction efficiency， matrix effects and stability study were all meet the requirement of the bioanalytical method. The AUC_(0-t) for Scutebarbatine A and Scutebarbatine B were (88.69±12.4)μg/L·h， (57.09±9.84)μg/L·h， respectively. And the Cmax for Scutebarbatine A and Scutebarbatine B were (10.22±1.31)ng/mL and (6.27±0.80)ng/mL. CONCLUSION?The method was simple， accurate， and sensitive， which could be used for the pharmacokinetic study of Scutebarbatine A and Scutebarbatine B after oral administration of Scutellaria barbata extract.