LC-MS/MS法测定硫酸特布他林在大鼠呼吸道组织中的分布  

Determination of the Distribution of Terbutaline Sulfate in Rat Respiratory Tract Tissues by LC-MS/MS

作　　者：杨娴 赵方红 侯海婷 YANG Xian;ZHAO Fanghong;HOU Haiting(Pharmaceutical Research Institute of Shijiazhuang No.4 Pharmaceutical Co.,Ltd.,Shijiazhuang 050000;Industrial Technology Research Institute of Chemical Sterile Preparations,Shijiazhuang 050000;Hebei Large Capacity Injection Engineering Technology Research Center,Shijiazhuang 050000)

机构地区：[1]石家庄四药有限公司研发中心,石家庄050000 [2]化学药品无菌制剂产业技术研究院,石家庄050000 [3]河北省大容量注射剂工程技术研究中心,石家庄050000

出　　处：《中国医药工业杂志》2022年第6期883-889,918,共8页Chinese Journal of Pharmaceuticals

摘　　要：建立了高效液相色谱-串联质谱(LC-MS/MS)法测定大鼠呼吸道组织中的硫酸特布他林(1),并考察吸入给药后,1在气管支气管、肺组织中的分布及体内的动态变化特征。色谱柱采用Eclipse XDB-C柱(4.6 mm×150 mm,5μm),采用电喷雾离子源(ESI),多反应监测(MRM)模式。结果显示,1分别在10.1~10100000 ng/g(气管支气管组织)和5~5000 ng/g(肺组织)内线性关系良好,定量限分别为10.1、5 ng/g。1在大鼠气管支气管组织以及肺组织中的日内RSD(n=6)均小于4%,满足生物样品定量分析要求。大鼠吸入给药后,1在大鼠气管支气管及肺组织内呈现相似的动态变化过程,给药后即可达最大浓度,随后快速消除。与肺组织相比,1在气管支气管组织中的分布浓度较高。建立的LC-MS/MS法能够快速、方便、准确地测定1,为1雾化吸入用溶液的临床合理用药提供了参考。A high-performance liquid chromatography-tandem mass spectrometry(LC-MS/MS)method was established for the determination of terbutaline sulfate(1)in the respiratory tract tissues of rats,and the distribution of 1 as well as the dynamic changes in vivo in tracheobronchial and lung tissues after inhalation administration was investigated.The Eclipse XDB-Ccolumn(4.6 mm×150 mm,5μm)was used,with the electrospray ionization(ESI)and multiple response monitoring(MRM)mode.The results showed that it was linear for 1 in the ranges of 10.1-10100 ng/g(tracheobronchialtissue)and 5-5000 ng/g(lung tissue),and the limits of quantification were 10.1 and 5 ng/g,respectively.The intra-day precision(n=6)of 1 in rat tracheobronchial and lung tissues were all less than 4%,which met the requirements of quantitative analysis of biological samples.After inhalation administration to rats,1 showed a similar dynamic change process in rat tracheobronchial and lung tissues,and the maximum concentration reached after administration,followed by rapid elimination.A higher concentration of 1 was found in tracheobronchial tissue,indicating its distribution was higher than that in lung tissue.The established LC-MS/MS method was fast,convenient and accurate,which provided a reference for the clinical rational drug use of 1 aerosol inhalation solution.

关 键 词：硫酸特布他林 雾化吸入 LC-MS/MS 气管支气管组织 肺组织 

分 类 号：R917[医药卫生—药物分析学]