目的 建立測定異丙托溴銨原料藥中有關(guān)物質(zhì)的高效液相色譜-二極管陣列檢測器-質(zhì)譜（HPLC-DAD-MS）法。方法 采用HPLC-MS法，Alltima C₁₈色譜柱（150 mm×4.6 mm，5 μm）；流動相：0.01 mol/L乙酸銨-乙腈，梯度洗脫；體積流量：0.25 mL/min；柱溫：35℃，進樣量：10 μL；檢測波長：220 nm。采用離子阱（ESI）正負(fù)離子模式進行檢測，源溫110℃；脫溶劑溫度350℃；脫溶劑氣體積流量600 L/h；錐孔氣體積流量50 L/h。結(jié)果 異丙托溴銨、托品酸、托品酸乙酯和雜質(zhì)F在0.01~10.00、0.012~12.000、0.083~8.300、0.05~5.00 mg/mL顯示良好的線性關(guān)系；異丙托溴銨、托品酸、托品酸乙酯和雜質(zhì)F的最低檢測限分別為1.46、0.57、4.16、5.03 ng；異丙托溴銨、雜質(zhì)C、托品酸乙酯和雜質(zhì)F的定量限分別為4.38、1.71、12.48、15.09 ng。結(jié)論 該方法靈敏度高、選擇性高、檢測限低，為異丙托溴銨的質(zhì)量控制提供依據(jù)。

Objective To establish determination of the related substances in ipratropium bromide active pharmaceutical ingredients by HPLC-DAD-MS. Methods HPLC-MS method was adopted. The determination was carried out on Alltima C₁₈ column (150 mm×4.6 mm, 5 μm),which mobile phase consisted of 0.01 mol/L ammonium acetate-acetonitrile with gradient elution. The column temperature was set at 35℃ at a flow rate of 0.25 mL/min. Injection volume was 10 μL. The detective wavelength was set at 220 nm. The ion trap (ESI) positive and negative ion mode was used as detection mode. Source temperature was set at 110℃ with desolvent temperature of 350℃. The flow rate of desolvent and cone gas were 600 and 50 L/h. Results There were good linear relationships of ipratropium bromide, tropic acid, tropic acid ethyl ester, and impurity F in the concentration ranges of 0.01-10.00, 0.012-12.000, 0.083-8.300, and 0.05-5.00 mg/mL, respectively. The limit of detection was 1.46, 0.57, 4.16, and 5.03 ng with limit of quantitation 4.38, 1.71, 12.48, and 15.09 ng, respectively. Conclusion The method has high sensitivity, high selectivity, and low detection limit which can be used in quantity control for ipratropium bromide active pharmaceutical ingredients.

國家重大新藥創(chuàng)制專項（2015ZX093001002009）