UPLC-MS/MS测定3种川芎茶调类制剂中马兜铃酸Ⅰ的含量

Content Determination of Aristolochic AcidⅠin Three Chuanxiong Chatiao Products by UPLC-MS/MS

目的:建立超高效液相色谱-质谱法(UPLC-MS/MS)同时测定川芎茶调丸、川芎茶调丸(浓缩丸)、川芎茶调颗粒中马兜铃酸Ⅰ的含量,对不同剂型中马兜铃酸Ⅰ的含量进行比较。方法:采用ACQUITY UPLC BEH C18色谱柱(100 mm×2.1 mm,1.7μm);以乙腈-0.1%甲酸水溶液为流动相梯度洗脱,流速为0.3 mL·min^(–1),电喷雾离子源,多反应监测,选择m/z 359.0→298.1和359.0→296.1离子对进行监测,对精密度、稳定性、重复性等进行验证的同时,对3种剂型共48批样品进行测定。结果:马兜铃酸Ⅰ在质量浓度为2.96~295.82 ng·mL^(–1)时与峰面积线性关系良好,r均大于0.999,平均回收率分别为93.36%、85.08%、90.13%,RSD分别为10.04%、6.04%、11.85%,定量限为0.0406~0.1577μg·g^(–1)。结论:该方法准确度、精密度、稳定性、线性关系良好,适用于川芎茶调类制剂中马兜铃酸Ⅰ的检测和分析;对于含有马兜铃酸类毒性成分中药的中药制剂更宜采用非原粉入药的方式。

Objective:An analytical method was established to simultaneously determine and compare the content of aristolochic acidⅠin three dosage forms of Chuanxiong Chatiao products,Chuanxiong Chatiao Pills,Chuanxiong Chatiao Pills(concentrated pills)and Chuanxiong Chatiao Granules,by ultra-performance liquid chromatography tandem mass spectrometry(UPLC-MS/MS).Methods:The samples were separated onACQUITYUPLC BEH C18(100 mm×2.1 mm,1.7μm)column and gradient elution was performed with acetonitrile-0.1%formic acid solution as a mobile phase.The flow rate was 0.3 mL·min^(–1),and triple quadrupole tandem mass spectroscopy was used as the detector.The samples were detected under multiple reaction monitoring(MRM)mode with electrospray ionization(ESI)in positive ion mode,and the mass to charge ratio(m/z)359.0→298.1 and 359.0→296.1 ion pairs were selected for monitoring.The contents of aristolochic acidⅠin three Chuanxiong Chatiao products from 48 batches were determined and the precision,stability and repeatability were verified.Results:The contents of aristolochic acidⅠhad a good linear relationship with the peak area when the mass concentration was 2.96-295.82 ng·mL^(–1),and the r value of the three products were all greater than 0.999.The average recoveries were 93.36%,85.08%,90.13%,and RSDs were10.04%,6.04%,11.85%,respectively.The limit of quantitation(LOQ)was 0.0406-0.1577μg·g^(–1).Conclusion:This method has good accuracy,precision,stability and linearity,and is suitable for the detection and analysis of aristolochic acidⅠin Chuanxiong Chatiao preparation.The results suggest that for the processing and preparation of traditional Chinese medicine containing toxic components such as aristolochic acid,it is more appropriate to use non original powder as the medicine.