根皮素在比格犬体内的药物动力学研究  

Pharmacokinetics of Phloretin in Beagle Dogs

作　　者：弥乐 沈歆[1] 周楠[1] 冯甜[1] 徐昕[1] 徐玥[1] 王力彬[1] 刘雪英[1] Mi Le Shen Xin Zhou Nan Feng Tian Xu Xin Xu Yue Wang Libin Liu Xueying(Department of Medicinal Chemistry, the Fourth Military Medical University, Xi＇ an 710032, China)

机构地区：[1]第四军医大学药物化学教研室,西安710032

出　　处：《中国药师》2017年第2期246-249,共4页China Pharmacist

基　　金：陕西省科技厅国际科技合作与交流计划项目(编号:2015KW-048)

摘　　要：目的:建立LC-MS/MS法测定根皮素在比格犬血浆中的浓度的方法,并将该方法应用于研究比格犬口服根皮素后的药动学行为。方法:以白藜芦醇为内标,血浆样品经乙酸乙酯萃取,富集生物样品中的根皮素,进行LC-MS/MS检测。色谱柱:Agilent EC C_(18)column(100 mm×4.6 mm,3.5μm),柱温:30℃,流动相:乙腈-水(95:5),流速:0.5 ml·min^(-1),采用电喷雾电离源(ESI),负离子多反应监测(MRM)扫描分析,根皮素和内标白藜芦醇的离子选择通道分别为m/z 273.0→m/z166.9,m/z 227.0→m/z 184.9;比格犬单剂量口服根皮素胶囊30 mg·kg^(-1),60 mg·kg^(-1),120 mg·kg^(-1)。于不同时间点取血测定血浆中药物的含量并利用DAS 2.0软件计算其药动学参数。结果:根皮素在50.0~125 000.0 ng·ml^(-1)范围内呈线性关系,平均回收率均大于93.15%,日内与日间精密度(RSD)均小于6.1%。比格犬口服30,60,120 mg·kg^(-1)的根皮素后,tmax分别为(180.0±69.28)min、240 min、240 min,C_(max)分别为(1 025.1±189.2)ng·ml^(-1)、(3 075.9±242.3)ng·ml^(-1)、(5 712.3±600.8)ng·ml^(-1)。给药剂量和AUC及C_(max)成正相关。结论:该法快速、精确、简便,可用于比格犬血浆中根皮素的测定及药动学研究。随着给药剂量的增加,AUC和C_(max)明显增加,t_(1/2)没有明显差异,CL/F减小。Objective： To develop an LC-MS/MS method for the quantitative determination of phloretin in plasma of Beagle dogs to study the pharmacokinetics of phloretin in Beagle dogs. Methods ： With resveratrol as the internal standard, LC-MS/MS was adopted to determine phloretin in plasma of Beagle dogs after the protein precipitation by ethyl acetate. An Agilent EC C18 column （ 100 mm × 4.6 mm, 3.5 μm） was used and the column temperature was 30℃. The mobile phase was acetonitrile-water （95：5 ） and the flow rate was 0.5 ml min-l. The injection volume was 5 μl. The samples were detected by tandem mass spectrometry with the electros- pray ionization （ESI） source in the multiple reaction monitoring （MRM） mode. The anion-selective channel of phloretin and the inter- nal standard was m/z 273.0--166.9 and 227.0-4184.9, respectively. The concentration of phloretin in plasma was at various time points tested after the oral administration of phloretin capsules at the dosage of 30 mg kg-1,60 mg kg-1 and 120 mg kg-1 and the data were processed with DAS. 2.0 software. Results： The standard calibration curve of phloreitn was linear over the range 50.0 125 000.0 ng ml-1. The recoveries obtained for phloreitn were greater than 93.15%. The intra-day and inter-day RSDs were less than 6.1%. After the oral administration at the dose of 30,60 and 120 mg kg-1, t was （ 180.0 ± 69.28）rain, 240 min and 240 min, and Cmax was （ 1025. 1 ± 189.2） ng ml -1 , （ 3075.9 ± 242.3） ng ml- l and （5712.3 ± 600.8） ng ml-1, respectively. There was a positive correlation between AUC and administration dosage. Conclusion： The method is rapid, accurate and simple, which is successfully applied in the pharmacokinetic study of phloretin in Beagle dogs. As the dosage increases, A UC and Cmax both increase with stable t1/2 and decreased CL/F.

关 键 词：根皮素 高效液相色谱串联质谱法 比格犬血浆 药物动力学 

分 类 号：R969.1[医药卫生—药理学]