LC―MSMS同时测定大鼠血浆中瑞香素西瑞香素与瑞香新素及其药代动力学研究.docVIP

LC―MSMS同时测定大鼠血浆中瑞香素西瑞香素与瑞香新素及其药代动力学研究 　　[摘要] 建立同?r测定大鼠灌胃祖师麻提取物后血浆中瑞香素、西瑞香素和瑞香新素的HPLC-MS/MS分析方法，并用于计算3个成分在大鼠体内的药代动力学参数。试验采用6只SD大鼠，口服给予祖师麻提取物 （瑞香素、西瑞香素和瑞香新素的给药量分别是88.40，3.24，4.28 mg?kg-1），以五味子醇甲为内标，用LC-MS/MS测定给药后血浆中药物浓度，绘制血药浓度-时间曲线，并用Kinetica 4.4软件计算相关药代动力学参数。试验结果显示，瑞香素、西瑞香素和瑞香新素的线性范围均为5～1 000 μg?L-1，方法学考察符合要求。日内、日间变异系数（RSD）均小于15%，精密度和准确度符合生物样品分析要求。瑞香素、西瑞香素和瑞香新素口服给药后的Tmax分别为4，2.92，2 h； Cmax分别为858.96，178.00，36.67 μg?L-1；AUC0-t分别为10 566.4，905.89，355.11 μg?L-1?h； 半衰期t1/2分别为5.19，3.50，4.95 h；平均驻留时间MRT分别为9.43，6.95，8.27 h。因此，该研究建立的LC-MS/MS分析方法准确灵敏，适于对SD大鼠口服祖师麻提取物后的瑞香素、西瑞香素和瑞香新素的药代动力学研究。 　　[关键词] LC-MS/MS； 祖师麻； 瑞香素； 西瑞香素； 瑞香新素； 药代动力学 　　[Abstract] To establish HPLC-MS/MS method for simultaneous determination of daphnetin， daphnoretin， and daphneticin in rat plasma after oral and intravenous administration of Daphne giraldii extract， and then use them in the calculation of pharmacokinetic parameters. Six sprague-dawley rats received intragastric administration of D. giraldii extract （daphnetin， daphnoretin and daphneticin were 88.40， 3.24 and 4.28 mg?kg， respectively）. Their drug plasma concentration was determined by LC-MS/MS with schisandrin as an internal standard to draw plasma concentration-time curve. The pharmacokinetic parameters were calculated by Kinetica 4.4. The results showed that the linear range was 5-1 000 μg?L-1 for daphnetin， daphnoretin and daphneticin， and the method ological test showed conformance to the requirements.The intraday and inter-day variable coefficients （RSD） were both less than 15.0%， indicating that both of legitimate precise and accuracy were consistent with the analysis requirements of biological samples. For daphnetin， the pharmacokinetic parameters Tmax， Cmax， AUC0?Ct， T1/2 and MRT were 4 h， 858.96 μg?L-1， 10 566.4 μg?L-1?h， 5.19 h and 9.43 h， respectively. For daphnoretin， the pharmacokinetic parameters Tmax， Cmax， AUC0?Ct， T1/2 and MRT were 2.92 h， 178.00 μg?L-1， 905.89 μg?L-1?h， 3.50 h and 6.95 h， respectively. For daphneticin， the