盐酸溴己新雾化气溶胶浓度测定及空气动力学粒径分布分析  

Quantification and Aerodynamics Particle Size Distribution of Bromhexine Hydrochloride Aerosol by LC-MS/MS

作　　者：朱狄峰 石萌 洪雅雯 赵剑岚 钱仁云 ZHU Di-feng;SHI Meng;HONG Ya-wen;ZHAO Jian-lan;QIAN Ren-yun(Center for Drug Safety Evaluation and Research,College of Pharmaceutial Sciences,Zhejiang University,Hangzhou 310058,China)

机构地区：[1]浙江大学药学院药物安全评价研究中心,杭州310058

出　　处：《中国药学杂志》2022年第21期1834-1841,共8页Chinese Pharmaceutical Journal

基　　金：浙江大学实验技术研究项目(SYB202134)。

摘　　要：目的建立液相色谱-三重四极杆串联质谱法(LC-MS/MS)测定盐酸溴己新雾化气溶胶浓度和分析其粒径分布,并比较注射器采样法及撞击器采样法的差异。方法采用BEH C_(18)色谱柱(2.1 mm×100 mm,1.7μm)分离,流动相为体积分数0.1%甲酸水和乙腈,分析时长为2 min,正离子模式下多反应监测测定。同时,对液质联用方法进行了方法学验证,采用该方法对注射器采样法及撞击器采样法采样获得的雾化气溶胶样本进行浓度测定,并基于撞击器采样法计算气溶胶的空气动力学粒径分布。结果建立的方法专属性、线性、定量限、精密度、准确度、提取回收率和稳定性良好。注射器采样法下总体气溶胶平均药物浓度为17.2 mg·m^(-3),撞击器采样法下则为16.8 mg·m^(-3)。基于撞击器采样法分析得到雾化时间在5和45 min的气溶胶平均质量中值空气动力学粒径(MMAD)分别为2.21和2.24μm,几何标准偏差(GSD)分别为2.76和2.75。结论本测定方法灵敏度高,精密度好,适用于盐酸溴己新雾化气溶胶浓度测定和粒径分布分析。两种样本采集方式的浓度测定结果基本一致,结果可为吸入制剂雾化气溶胶分析提供参考。OBJECTIVE To establish a liquid chromatography-tandem mass spectrometry(LC-MS/MS)method to determine bromhexine hydrochloride aerosols′concentration and compare the methods of syringe sampling and impactor sampling in the application of aerosol particle size distribution analysis.METHODS The chromatographic separation was performed using a BEH C_(18) column(2.1 mm×100 mm,1.7μm)with the mobile phase consisting of 0.1%formic acid in water and acetonitrile,and each separation was done in 2 minutes.The MS detection used multiple reaction monitoring(MSM)scan in positive ion mode.The validated method was applied to measure the concentration of the aerosol samples obtained by syringe sampling or impactor sampling.The aerodynamic particle size distribution(APSD)was then calculated based on the impactor sampling results.RESULTS The established method demonstrated appropriate specificity,linearity,quantification limit,precision,accuracy,extraction recovery,and stability.The average aerosol drug concentration was 17.2 mg·m^(-3) with syringe sampling and 16.8 mg·m^(-3) with impactor sampling.Based on the impactor sampling method,at atomization times of 5 minutes and 45 minutes,the mass median aerodynamic diameter(MMAD)of the aerosols was 2.21μm and 2.24μm,and the geometric standard deviation(GSD)was 2.76 and 2.75,respectively.CONCLUSION The current study establishes a high sensitivity and precision method,which is suitable for determining bromhexine hydrochloride atomized aerosol concentration and particle size distribution.The two sample collection methods performes similarly in the concentration measurement,and these results could provide a reference for the analysis of aerosols in inhaled formulations in the future.

关 键 词：液相色谱-串联质谱法 盐酸溴己新 撞击器采样法 注射器采样法 空气动力学粒径分布 雾化气溶胶 

分 类 号：R917[医药卫生—药物分析学]