UHPLC-MS/MS法分析氯化乙酰甲胆碱雾化气溶胶浓度  

Quantification of Aerosol Content of Methacholine Chloride Powder by UHPLC-MS/MS

作　　者：朱狄峰 赵剑岚 洪雅雯 钱仁云 陈超 平丽 ZHU Di-feng;ZHAO Jian-lan;HONG Ya-wen;QIAN Ren-yun;CHEN Chao;PING Li(Center for Drug Safety Evaluation and Research,College of Pharmaceutical 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,浙江杭州310058

出　　处：《分析测试学报》2021年第8期1145-1150,共6页Journal of Instrumental Analysis

基　　金：浙江省自然科学基金项目(LY17H310004)。

摘　　要：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,1.7μm)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5μL,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(UHPLCMS/MS)method was established for the determination of aerosol content of methacholine chloride for inhalation solution.The sample was separated on an ACQUITY BEH C18(2.1 mm×100 mm,1.7μm)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 5μL,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.

关 键 词：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 

分 类 号：O657.7[理学—分析化学] R914.1[理学—化学]