LC-MS/MS法测定Beagle犬血浆中妥洛特罗质量浓度及其在药动学研究中的应用  

Determination of tulobuterol in Beagle dog plasma by LC-MS / MS and application to a pharmacokinetics study

作　　者：刘慧[1] 刘茜[1] 赵丽蓉[1] 殷腾瑞 武惠斌 聂红梅 

机构地区：[1]沈阳药科大学药学院,辽宁沈阳110016 [2]河南羚锐制药股份有限公司北京药物研究院,北京100070

出　　处：《沈阳药科大学学报》2015年第1期45-49,69,共6页Journal of Shenyang Pharmaceutical University

摘　　要：目的建立LC-MS/MS法测定Beagle犬血浆中妥洛特罗的质量浓度,研究Beagle犬给予妥洛特罗贴剂后的药动学特征。方法血浆经乙酸乙酯-二氯甲烷(体积比4∶1)提取。色谱柱为Agilent TC-C18柱,流动相为甲醇-体积分数1%甲酸溶液(体积比67∶33),流速为0.5 m L·min-1,进样量为30μL。质谱采用多反应监测模式(multiple reaction monitoring,MRM),电喷雾离子源,分析时间4.5 min。采用DAS 2.0软件以非房室模型计算药动学参数。结果妥洛特罗质量浓度在0.1~10μg·L-1内与峰面积呈良好的线性关系,定量下限为0.1μg·L-1。日内、日间精密度(RSD)均小于15%,准确度(RE)为-4.27%^-0.60%,方法回收率大于(82.0±6.35)%。健康Beagle犬给予妥洛特罗贴剂(规格为每贴2 mg)后主要药动学参数:tmax为(5.25±1.49)h,ρmax为(7.82±1.98)μg·L-1,t1/2为(5.59±2.37)h;采用梯形法计算,AUC0-t为(99.26±15.05)μg·h·L-1,AUC0-∞为(101.94±14.99)μg·h·L-1。结论该方法可用于妥洛特罗临床前药动学研究。Objective To develop an LC-MS/MS method for the study of pharmacokinetics of tulobuterol in Beagle dogs. Methods The plasma samples were extracted by liquid-liquid extraction with mixture solvent composed of 25% dichloromethane in ethylacetate. The mobile phase was methanol - 1% formic acid （V： V =67：33 ）. The separation was performed on a reversed-phase Agilent TC-C_18 column. Detection was carried out by multiple reactions monitoring with an API 2 000 triple quadrupole mass spectrometer equipped with an electrospray ionization source. The analysis time was 4.5 min. Results The linear calibration curve was obtained in the range of 0. 1 - 10 μg · L^-1 for tulobuterol. The lower limit of quantitation was 0. 1 μg · L^-1. The intra-day and inter-day precision（RSD） were less than 15 %, and the accuracy （relative er- ror） were between -4.27% and -0.60%. The main pharmacokinetics parameters of sarpogrelate were as follows ： tmax was （ 5.25±1.49 ） h; Pmax was （ 7.82 ±1.98 ） μg · L^-1 ; t1/2 was （ 5.59 ± 2.37 ） h; AUC_0-t was （99.26 ± 15.05） μg·h·L^-1 ,AUC_0-∞ was（ 101. 94 ± 14. 99） μg·h·L^-1. Conclusion The method can be uti- lized for the pharmacokinetics study of tulobuterol in Beagle dogs.

关 键 词：妥洛特罗 BEAGLE犬 LC-MS/MS 药动学 

分 类 号：R969.1[医药卫生—药理学]