胡伊力格其;曹萨丽;林龙飞;付京;董晓旭;杨春静;张淼;倪健;
HU Yi-yi-li-ge-qi;CAO Sa-li;LIN Long-fei;FU Jing;DONG Xiao-xu;YANG Chun-jing;ZHANG Miao;NI Jian;College of Traditional Mongolia Medicine and pharmacy,Inner Mongolia University for Nationalities;Beijing University of Chinese Medicine;

• 1:内蒙古民族大学蒙医药学院
• 2:北京中医药大学

摘要(Abstract)：

建立同时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)),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5¹ 000μg·L1 000μg·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T_(max)分别为4,2.92,2 h;C_(max)分别为858.96,178.00,36.67μg·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T_(max)分别为4,2.92,2 h;C_(max)分别为858.96,178.00,36.67μg·L^(-1);AUC_(0-t)分别为10 566.4,905.89,355.11μg·L(-1);AUC_(0-t)分别为10 566.4,905.89,355.11μg·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。
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)·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。
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–t,T_(1/2) and MRT were 4 h,858. 96 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–t,T_(1/2) and MRT were 4 h,858. 96 μg·L^(-1),10 566. 4 μg·L(-1),10 566. 4 μg·L^(-1)·h,5. 19 h and9. 43 h,respectively. For daphnoretin,the pharmacokinetic parameters T_(max),C_(max),AUC_(0–t),T_(1/2) and MRT were 2. 92 h,178. 00 μg· L(-1)·h,5. 19 h and9. 43 h,respectively. For daphnoretin,the pharmacokinetic parameters T_(max),C_(max),AUC_(0–t),T_(1/2) and MRT were 2. 92 h,178. 00 μg· L^(-1),905. 89 μg· L(-1),905. 89 μg· L^(-1)· h,3. 50 h and 6. 95 h,respectively. For daphneticin,the pharmacokinetic parameters T_(max),C_(max),A UC_(0–t),T_(1/2) and MRT were 2 h,36. 67 μg·L(-1)· h,3. 50 h and 6. 95 h,respectively. For daphneticin,the pharmacokinetic parameters T_(max),C_(max),A UC_(0–t),T_(1/2) and MRT were 2 h,36. 67 μg·L^(-1),355. 11 μg·L(-1),355. 11 μg·L^(-1)·h,4. 95 h and 8. 27 h,respectively. The LC-MS/MS analysis method established in this study was proved to be so accurate and sensitive that it can be applied to the pharmacokinetic study of daphnetin,daphnoretin and daphneticin.

关键词(KeyWords)： LC-MS/MS;祖师麻;瑞香素;西瑞香素;瑞香新素;药代动力学
LC-MS/MS;Daphne giraldii;daphnetin;daphnoretin;daphneticin;pharmacokinetic

Abstract:

Keywords:

基金项目(Foundation):

作者(Authors): 胡伊力格其;曹萨丽;林龙飞;付京;董晓旭;杨春静;张淼;倪健;
HU Yi-yi-li-ge-qi;CAO Sa-li;LIN Long-fei;FU Jing;DONG Xiao-xu;YANG Chun-jing;ZHANG Miao;NI Jian;College of Traditional Mongolia Medicine and pharmacy,Inner Mongolia University for Nationalities;Beijing University of Chinese Medicine;

DOI: 10.19540/j.cnki.cjcmm.20170307.003

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