LC-MS/MS法检测皮肤科常用中药制剂中添加的7种抗组胺药物  

Simultaneous determination of 7 antihistamine agents added into traditional Chinese medicine preparation by LC-MS/MS

作　　者：叶林虎 徐松 王丽莎[2] 贺梅 常琪[2] 

机构地区：[1]毕节市第一人民医院,毕节551700 [2]中国医学科学院、北京协和医学院药用植物研究所,北京100193

出　　处：《药物分析杂志》2016年第11期2022-2028,共7页Chinese Journal of Pharmaceutical Analysis

基　　金：毕节市科技局资助项目(毕科合字[2015]51号,毕科合[2015]62号);贵州省科学技术基金项目(黔科合J字[2015]2004号);重大新药创制“科技重大专项”(2012ZX09301002-001)

摘　　要：目的:建立一种灵敏、快捷的LC-MS/MS方法,快速检测皮肤科常用中药制剂中添加的氯雷他定、盐酸苯海拉明、盐酸赛庚啶、盐酸西替利嗪、盐酸异丙嗪、咪唑斯汀、马来酸氯苯那敏7种抗组胺化学药物。方法:片剂、软膏和洗剂等样品均采用甲醇超声溶解、离心的方法进行前处理。LC-MS/MS条件:采用Agilent Eclipse Plus C_(18)(2.1 mm×50 mm,3.5μm)色谱柱,以含0.1%甲酸的乙腈(A)-含0.1%甲酸的水(B)为流动相,进行梯度洗脱(0~0.1 min,5%A→95%A;0.1~4.1 min,95%A;4.1~8 min,95%A→5%A),流速0.4 mL·min^(-1),柱温40℃;选择ESI正离子模式扫描,信号采集方式为多反应监测(MRM)。最后通过比较MRM通道中样品峰与对照品峰及色谱保留时间等信息确定受试样品是否被添加上述抗组胺药物。结果:在一定浓度范围内,氯雷他定、盐酸苯海拉明、盐酸赛庚啶、盐酸西替利嗪、盐酸异丙嗪、咪唑斯汀和马来酸氯苯那敏7种抗组胺化学药物有较好的线性和稳定性,且检测下限均在0.5~2.5 ng·mL^(-1),定量下限均在1~5 ng·mL^(-1),回收率均在86.2%~112.5%范围内。在9种中药制剂中,4种被检出添加了抗组胺药物。结论:本方法经方法学验证,可作为皮肤科中药制剂中检出添加抗组胺化学药物的检测方法。Objective： To establish a rapid and accurate LC-MS/MS method for the determination of 7 chemical antihistamine agents, including loratadine, diphenhydramine hydrochloride, cyproheptadine hydrochloride, cetirizine hydrochloride, promethazine hydrochloride, mizolastine, and chlorpheniramine maleate, which were added into the traditional Chinese medicine preparations of dermatology. Methods： Samples were dissolved in methanol by ultrasonic and suffered centrifugation, and then separated on an Agilent Eclipse Plus C18 （ 2. 1 mm × 50 mm, 3.5 μm ）maintained at 40 ℃. The mobile phase consisted of 0. 1% formic acid in acetonitrile （ A ） and in water （ B ） at a flow rate of 0. 4 mL. min-1. Phase A was linearly increased from 5% to 95% over 0. 1 min, maintained at 95% for an additional 4 min, and then decreased to 5% over 4 min for re-equilibration. A positive ion and multiple reaction monitoring（ MRM ） mode was used for the scanning, and the obtained peak areas were used for the calculation. In addition, whether the antihistamine agents were illegally adulterated in traditional Chinese medicine preparations were determined by the chromatographic peak and retention time. Results： In certain concentrations, the detection method showed good linearity. The limits of qualitative and quantitative were in the range of 0. 5- 2. 5 and 1-5 ng. mL-1. The recoveries were in the range of 86.2%-112. 5%. In 9 kinds of traditional Chinese medicine preparations, 4 preparations were detected to be added to antihistamines. Conclusion： The method is confirmed by methodology validation that it can be used for the determination of added chemical antihistamine agents in traditional Chinese medicine preparations of dermatology.

关 键 词：抗组胺药物 氯雷他定 盐酸苯海拉明 盐酸赛庚啶 盐酸西替利嗪 盐酸异丙嗪 咪唑斯汀 马来酸氯苯那敏 非法添加 中药制剂 快速测定 液相色谱串联质谱 

分 类 号：R917[医药卫生—药物分析学]