珍菊降压片有关物质初探

目的： 建立中西药复方制剂珍菊降压片中氢氯噻嗪主要降解产物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? UPLC? C₁₈色谱柱（1.6 μm，3.0 mm×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/z 284.00→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 CORTECS? UPLC? C₁₈ column(1.6 μm,3.0 mm×100 mm)was applied with a mobile phase consisting of 0.1% formic acid acetonitrile-0.1% formic acid H₂O 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.

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