液相色谱-串联质谱法研究丁苯酞在犬血浆的药代动力学  

Study on pharmacokinetics of butyphthalide in dog plasma by LC-MS/MS

作　　者：徐玲玲 王芳 贾庆文 戚敏 XU Ling-ling;WANG Fang;JIA Qing-wen;QI Min(Shandong Academy of Pharmaceutical Sciences,Jinan 250101,China)

机构地区：[1]山东省药学科学院,济南250101

出　　处：《药物分析杂志》2018年第8期1405-1409,共5页Chinese Journal of Pharmaceutical Analysis

摘　　要：目的:建立液相色谱-串联质谱法测定犬血浆中丁苯酞的浓度。方法:6只Beagle犬,单剂量灌胃丁苯酞(20 mg·kg^(-1)),犬血浆样本以乙腈沉淀蛋白后,选用Agilent Poroshell 120 EC-C_(18)色谱柱(2.1 mm×50 mm,2.7μm),流动相为水-乙腈(65∶35),流速0.4 mL·min^(-1),柱温40℃,进样量5μL,分析时间4.5 min;选用Agilent 6460三重四极杆串联质谱仪,离子化方式:电喷雾-正离子(API-ES),干燥气为N_2,干燥气流速11 L·min^(-1),干燥气压力0.31 MPa,干燥气温度350℃,毛细管电压4kV。监测方式为MRM,丁苯酞监测离子对m/z 191.0/144.9,地西泮监测离子对m/z 285.1/193.1。结果:本分析方法专属性良好;丁苯酞质量浓度在2～2 000 ng·mL^(-1)范围内线性关系符合要求;准确度均在85%～115%,精密度RSD在15%内。主要药代动学参数:T_(max)为(0.52±0.09)h,C_(max)为(1 625±273)μg·L^(-1),AUC_(0-24 h)为(5 076±751)μg·L^(-1)·h^(-1),t_(1/2)为(1.26±0.11)h。结论:本法适用于犬血浆中丁苯酞浓度的测定,可用于丁苯酞犬体内药代动力学研究。Objective：To establish a liquid chromatography tandem mass spectrometry method for the determination of butyphthalide in dog plasma. Methods：Six beagle dogs were treated with a single dose of 20 mg·kg-1. After protein precipitation with acetonitrile,butyphthalide and diazepam were separated on an Agilent Poroshell 120 EC-C18 column（2.1 mm×50 mm,2.7 μm）,with acetonitrile-water（35∶65）as the mobile phase at a flow rate of 0.4 mL·min-1,the column temperature was 40 ℃,the sample volume was 5μL,and the analysis time was 4.5 min; Agilent 6460 triple quadrupole series mass spectrometer was used with ionization mode was electrospray-positive ion（API-ES）,dry gas was N2,drying gas velocity was 11 L·min-1,drying gas pressure was 0.31MPa,drying gas temperature was 350 ℃,capillary voltage was 4 k V; Monitoring mode： multiple reaction monitoring（MRM）mode. The MRM transitions of m/z 191.0-144.9 and m/z 285.1-193.1 were used to quantify butyphthalide and diazepam,respectively. Results：The analytical method was of good specificity. The linear relationship of butylphthalide in the range of 2-2 000 ng·mL-1 met the requirements. The accuracy was 85%-115% and the precision RSD was within 15%. The main pharmacokinetic parameters were as follows：Tmax was（0.52±0.09） h,Cmax was（1 625±273）μg·L-1,AUC0-24 h was（5 076±751）μg·L-1·h-1,t1/2 was（1.26±0.11） h. Conclusion：The method can be applied to the determination of butyphthalide in dog plasma,and is suitable to the pharmacokinetic study of butyphthalide in dogs.

关 键 词：丁苯酞 犬血浆 血药浓度 液相色谱-串联质谱法 药代动力学 

分 类 号：R917[医药卫生—药物分析学]