浙江大学 药学院 药物安全评价研究中心,浙江 杭州 310058
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朱狄峰,赵剑岚,洪雅雯等.UHPLC-MS/MS法分析氯化乙酰甲胆碱雾化气溶胶浓度[J].分析测试学报,2021,40(08):1145-1150.
ZHU Di-feng,ZHAO Jian-lan,HONG Ya-wen,et al.Quantification of Aerosol Content of Methacholine Chloride Powder by UHPLC-MS/MS[J].Journal of Instrumental Analysis,2021,40(08):1145-1150.
朱狄峰,赵剑岚,洪雅雯等.UHPLC-MS/MS法分析氯化乙酰甲胆碱雾化气溶胶浓度[J].分析测试学报,2021,40(08):1145-1150. DOI: 10.19969/j.fxcsxb.20091102.
ZHU Di-feng,ZHAO Jian-lan,HONG Ya-wen,et al.Quantification of Aerosol Content of Methacholine Chloride Powder by UHPLC-MS/MS[J].Journal of Instrumental Analysis,2021,40(08):1145-1150. DOI: 10.19969/j.fxcsxb.20091102.
建立了超高效液相色谱-三重四极杆质谱(UHPLC-MS/MS)测定吸入雾化装置中氯化乙酰甲胆碱气溶胶药物浓度的方法。采用ACQUITY BEH C,18,(2.1 mm × 100 mm,1.7 μm)色谱柱,以0.1%甲酸水和乙腈作为流动相梯度洗脱,流速为0.3 mL/min,进样量为5 μL,分析时间为5 min,柱温为40 ℃,多反应监测(MRM)正离子模式测定。同时,对专属性、线性、仪器精密度、加标回收率、提取回收率和稳定性分别进行了考察。结果表明,氯化乙酰甲胆碱在10~100 ng/mL质量浓度范围内线性良好(,r ,> 0.999),定量下限为10 ng/mL;氯化乙酰甲胆碱雾化气溶胶的平均加标回收率为99.2%,平均相对标准偏差(RSD)为0.80%;雾化气溶胶的平均提取回收率为95.7%。在吸入暴露装置中雾化1 min后,气溶胶的平均药物浓度为608.1 mg/m,3,,上、中、下位置的RSD为1.2%,表明雾化1 min氯化乙酰甲胆碱气溶胶浓度即达到均一。该方法灵敏度高,精密度好,适用于氯化乙酰甲胆碱雾化气溶胶的浓度测定,也可为吸入制剂雾化气溶胶供试品分析提供参考。
An ultra-high performance liquid chromatography-tandem mass spectrometric(UHPLC-MS/MS) method was established for the determination of aerosol content of methacholine chloride for inhalation solution. The sample was separated on an ACQUITY BEH C,18,(2.1 mm × 100 mm, 1.7 μm) column by gradient elution, using 0.1% formic acid water and acetonitrile as the mobile phases with a flow rate of 0.3 mL/min, an injection volume of 5 μL, an analysis time of 5 min and a column temperature of 40 ℃, and finally determined in multiple-reaction monitoring(MRM) mode. Meanwhile, the specificity, linearity, instrument precision, spiked recovery, extraction recovery and stability were investigated. Methacholine chloride was linear in the range of 10-100 ng/mL(,r ,> 0.999). The limit of quantitation was 10 ng/mL. The recovery for methacholine chloride in aerosols was 99.2% with a relative standard deviation(RSD) of 0.80%. The extraction efficiency for methacholine chloride was 95.7%. After atomizated for 1 min in the inhalation exposure device, the average content of methacholine chloride in the aerosols was 608.1 mg/m,3,. RSD of the upper, middle and lower positions was 1.2%. It indicated that the content of methacholine chloride in the aerosols was uniform after 1 min atomization. The method is sensitive and precise, and is suitable for the determination of aerosol content of methacholine chloride powder for inhalation solution, and it also could be used as a reference for the analysis of other aerosol samples for inhalation.
超高效液相色谱-串联质谱法氯化乙酰甲胆碱雾化气溶胶吸入制剂
ultra-high performance liquid chromatography-tandem mass spectrometrymethacholine chlorideatomization aerosolinhalation
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