珍菊降压片有关物质初探  

Preliminary study on related substances in Zhenju Jiangya tablets

作　　者：郭东晓 孙沛霖 栾永福 臧远芳 刘洪超 倪叩 林永强 GUO Dong-xiao;SUN Pei-lin;LUAN Yong-fu;ZANG Yuan-fang;LIU Hong-chao;NI Kou;LIN Yong-qiang(NMPA Key Laboratory for Quality Evaluation of Gelatin PnxJucts,Shandong Institute for Food and Drug Control,Jinan 250101,China;Hubei Institute for Drug Control,Wuhan 430075,China)

机构地区：[1]山东省食品药品检验研究院国家药品监督管理局胶类产品质量评价重点实验室,济南250101 [2]湖北省药品监督检验研究院,武汉430075

出　　处：《药物分析杂志》2020年第6期1121-1130,共10页Chinese Journal of Pharmaceutical Analysis

基　　金：山东省自然科学基金项目(ZR2013HM074)。

摘　　要：目的:建立中西药复方制剂珍菊降压片中氢氯塞嗪主要降解产物4-氨基-6-氯-1,3-苯二磺酰胺的高效液相色谱-串联质谱定量检测方法。方法:采用Waters CORTECS(R) UPLC(R) C18色谱柱(1.6μm,3.0mm×100 mm),流动相为含0.1%甲酸的乙腈溶液-0.1%甲酸溶液,梯度洗脱;质谱采用电喷雾负离子模式(ESI-),多反应监测(MRM)定量分析,以m/z284.00→205.15作为定量离子对。结果:4-氨基-6-氯-1,3-苯二磺酰胺进样量在0.88-13.20 ng内线性关系良好,回归方程Y=3.041×105 X-2.841×105,相关系数r=0.999 6;平均回收率(n=6)为106.5%,RSD为0.67%。在收集的49份样品中,3家企业6份样品超过了拟定限度。通过对不同收集地区不同包装材料的样品测定结果进行分析,以及加速稳定性试验确认,温湿度和包装材料对样品中氢氯噻嗪的稳定性有显著影响。结论:本文建立的珍菊降压片中有关物质的测定方法准确、可靠,可用于检测珍菊降压片中4-氨基-6-氯-1,3-苯二磺酰胺的含量。Objective:To establish an HPLC-MS/MS method for the quantitative analysis of 4-amino-6-chloro-1,3-benzenedisulfonamide,a main degradation product of hydrochlorothiazide,in Zhenju Jiangya tablets which is a compound preparation of traditional Chinese medicine and chemical drug.Methods:A Waters CORTECSRUPLCRC18 column(1.6 μm,3.0 mm × 100 mm) was applied with a mobile phase consisting of0.1% formic acid acetonitrile-0.1% formic acid H2 O in gradient elution mode.The mass spectral analysis was performed in a negative electrospray ionization mode(ESI-),and scanned by a multiple reaction monitoring mode(MRM).The precursor/product ion pair used for quantification was m/z 284.00→205.15.Results:A good linear relationship was obtained in the range of 0.88-13.20 ng for 4-amino-6-chloro-1,3-benzenedisulfonamide,with the linear regression equation of Y=3.041 × 105 X-2.841 × 105(r=0.999 6);the average recovery was 106.5%(RSD=0.67%,n=6).Among 49 samples of Zhenju Jiangya tablets,the analysis results of 6 samples from 3 enterprises exceeded the proposed limit.Comparing the determination results of samples from different collection areas with different packaging materials,stability of hydrochlorothiazide in Zhenju Jiangya tablets was significantly impacted by temperature,humidity,and packaging materials,which was also confirmed by the accelerated stability test.Conclusion:This method is accurate and reliable,which can be applied to detect the content of 4-amino-6-chloro-1,3-benzenedisulfonamide in Zhenju Jiangya tablets.

关 键 词：中西药复方制剂 有关物质 珍菊降压片 氢氯噻嗪 4-氨基-6-氯-1 3-苯二磺酰胺 高效液相色谱-串联质谱 

分 类 号：R917[医药卫生—药物分析学]