HPLC法分析复方异丙托溴铵溶液雾化气溶胶成分

建立HPLC法同时测定吸入用复方异丙托溴铵溶液雾化气溶胶中硫酸沙丁胺醇和异丙托溴铵两组分的含量。采用C₁₈(4.6mm×250 mm,5μm)色谱柱,流动相为1.2 g/L的1-庚烷磺酸钠溶液(磷酸调节pH 3.2左右)(A)-乙腈(B),等度洗脱,流速为1.0 mL/min,进样量为50μL,分析时间15 min,柱温40℃,检测波长为210 nm。结果表明,硫酸沙丁胺醇和异丙托溴铵分别在0.1~2.0 mg/L和0.075~2.4 mg/L浓度范围线性良好(r值均大于0.999)。复方异丙托溴铵溶液雾化气溶胶中硫酸沙丁胺醇和异丙托溴铵加样回收率分别为97.8%和102.3%。雾化气溶胶中硫酸沙丁胺醇和异丙托溴铵提取方法的回收率分别为96.1%和97.1%。在吸入暴露装置中经雾化5 min和35 min后,气溶胶中硫酸沙丁胺醇含量分别为22.39和3.21 mg/m³,异丙托溴铵含量分别为22.34和3.23 mg/m³,回收率均不低于99.5%,RSD不大于1.9%,表明雾化5 min即达到稳定。本方法适用于吸入用复方异丙托溴铵溶液雾化气溶胶的药物含量测定,也可为吸入制剂雾化气溶胶供试品分析提供参考。

Determination of the components in aerosols of compound ipratropium bromide solution for inhalation by high performance liquid chromatography

A method of high performance liquid chromatography(HPLC)was established for the determination of ipratropium bromide and salbutamol sulfate in aerosols of compound ipratropium bromide solution for inhalation.C18(4.6 mm×250 mm,5μm)column was used,and the mobile phase was 1.2 g/L sodium 1-heptanesulfonate solution(about pH 3.2 adjusted with phosphoric acid)(A)-acetonitrile(B).For degree elution,the flow rate was 1.0 mL/min,the injection volume was 50μL,the analysis time was 15 min,the column temperature was 40℃,and the detection wavelength was 210 nm.The results showed that salbutamol sulfate and ipratropium bromide were linear in the range of 0.1-2.0 mg/L and 0.075-2.4 mg/L,respectively(r values were greater than 0.999).The recoveries were 97.8%and 102.3%for salbutamol sulfate and ipratropium bromide in aerosols,respectively.The extraction efficiencies of salbutamol sulfate and ipratropium bromide were 96.1%and 97.1%,respectively.After atomization for 5 min and 35 min in the inhalation exposure device,the contents of salbutamol sulfate in the aerosols were 22.39 and 3.21 mg/m³,and those of ipratropium bromide were 22.34 and 3.23 mg/m³,respectively.The recovery rates were not less than 99.5%,and RSDs were not more than 1.9%.It indicated that the content in the aerosols was stable after 5 min atomization.The method is suitable for the determination of 2 components in the aerosols of compound ipratropium bromide solution for inhalation,and it can be used for reference in analyzing other aerosol samples for inhalation.