吸入用复方异丙托溴铵溶液在大鼠呼吸道的组织分布  

Tissue Distribution of Compound Ipratropium Bromide Solution for Inhalation in Respiratory Tract of Rats

作　　者：左亚茹 侯海婷 赵方红 杨娴 ZUO Yaru;HOU Haiting;ZHAO Fanghong;YANG Xian(Pharmaceutical Research Institute of Shijiazhuang No.4 Pharmaceutical Co.,Ltd.,Shijiazhuang 052100;Industrial Technology Research Institute of Chemical Sterile Preparations,Shijiazhuang 051430;Postdoctoral Research Workstation of Shijiazhuang No.4 Pharmaceutical Co.,Ltd,Shijiazhuang 052100)

机构地区：[1]石家庄四药有限公司研发中心,河北石家庄052100 [2]化学药品无菌制剂产业技术研究院,河北石家庄051430 [3]石家庄四药有限公司博士后科研工作站,河北石家庄052100

出　　处：《中国医药工业杂志》2023年第7期1095-1103,共9页Chinese Journal of Pharmaceuticals

基　　金：河北省创新能力提升计划项目(225A2704D);河北省高层次人才资助项目(B2022003039)。

摘　　要：该研究建立了复方异丙托溴铵溶液(F)中异丙托溴铵(1)及硫酸沙丁胺醇(2)的LC-MS/MS分析方法,并测量了1和2在大鼠气管支气管、肺组织的分布。结果显示,大鼠吸入F后1与2在气管支气管中的浓度线性范围均为2~800 ng/g;在肺中的浓度线性范围均为1~400 ng/g。大鼠吸入给药后,1和2在气管支气管和肺内呈现相似的动态变化过程,给药后即可达峰浓度,随后快速消除。与肺相比,2在气管支气管中分布较多(P<0.05),1在气管支气管的浓度与肺组织浓度无显著差异(P>0.05)。所建立的LC-MS/MS测量方法简便、灵敏、准确,可用于大鼠体内组织的药物分布研究,为研究F的体内药动学研究提供了新方法,为其临床合理用药提供了数据参考。An LC-MS/MS analytical method was established to determine ipratropium bromide(1)and salbutamol sulfate(2)in compound ipratropium bromide solution(F),thus it was used to determine the distributions of 1 and 2 in tracheobronchial and pulmonary tissues of rats.The results showed that the linear concentration ranges of 1 and 2 in the trachea,bronchus and lung of rats inhaled of F were 2-800 and 1-400 ng/g,respectively.The dynamic changes of 1 and 2 in rat tracheobronchial and lung tissues showed similar processes,reaching the maximum concentration after administration and followed by rapid elimination.Compound 2 showed higher distribution in trachea and bronchus(P<0.05)than that in lung tissue,and the concentrations of 1 in tracheobronchial and lung tissues showed no significant difference(P>0.05).The developed LC-MS/MS method was simple,sensitive,accurate,and could be used to determine drug distributions in rat tissues.This study provided a new evaluation method for the pharmacokinetics of F in vivo and a reference for clinical rational drug use.

关 键 词：异丙托溴铵 硫酸沙丁胺醇 雾化吸入 气管支气管 肺 

分 类 号：R965[医药卫生—药理学]