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

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.