复方氨酚苯海拉明片有关物质及原辅料相容性研究

目的：建立梯度洗脱-HPLC法测定复方氨酚苯海拉明片剂中有关物质，并对国内7家企业复方氨酚苯海拉明片的有关物质进行分析。方法：采用Waters XBridge C₁₈（4.6 mm×250 mm，5μm）色谱柱，流动相为0.01 mol·L^-1的磷酸二氢铵溶液（用磷酸调节pH至2.1±0.05）-乙腈，梯度洗脱，流速为1.0 mL·min^-1，检测波长为205 nm，柱温为30℃。已知杂质对氨基苯酚和盐酸苯海拉明杂质A采用外标法，其他已知杂质为加校正因子的自身对照法，未知杂质为不加校正因子的自身对照法。结果：主峰与18个已知杂质峰及其他降解杂质峰的分离度良好，4个主成分与18个已知杂质的线性关系良好，18个已知杂质的平均回收率为98.3%~101.6%，精密度、重复性、稳定性、专属性均良好。国内大多数企业片剂中单个杂质量在1.0%以下，杂质总量在2.0%以下。辅料羧甲基淀粉钠和盐酸苯海拉明配伍会使盐酸苯海拉明杂质A的量增加。结论：本法灵敏度高，专属性好，可用于复方氨酚苯海拉明片剂中有关物质的分析研究。  

Objective: To establish a gradient elution-HPLC method for related substance test of compound paracetamol and diphenhydramine hydrochloride tablets, and also to study the profile of related substances of 7 manufacturers' tablets from domestic. Methods: The separation was performed on Waters XBridge C₁₈ (4.6 mm×250 mm, 5 μm)column with gradient elution of mobile phase consisting of 0.01 mol·L^-1 ammonium dihydrogen phosphate (pH 2.1±0.05)-acetonitrile at the flow rate of 1.0 mL·min^-1. Detection wavelength was set at 205 nm, and column temperature was 30℃. The determination of p-aminophenol and diphenhydramine hydrochlorideimpurity A was quantitatively analyzed by external standard method. The determination of the other known impurities was quantitatively analyzed by main component self-compare with relative response factor. The unknown impurities were determined by main component self-compare method without relative response factor. Results: The separation degree among four main components, 18 kinds of known impurities and other degradated impurities was greater than 1.0. The linear relationship, precision, reproducibility, stability and specificity tests of four main components and 18 kinds of known impurities were all good. The average recoveries of 18 known impurities were between 98.3% and 101.6%. The single impurity content of compound paracetamol and diphenhydramine hydrochloride tablets from most of the domestic manufacturers was below 1.0%, and the content of total impurities was below 2.0%. The amount of diphenhydramine hydrochlorideimpurity A will increase on the condition of the present of the excipient of carboxymethyl starch sodium. Conclusion: The gradient elutionHPLC method is sensitive, and the specificity is good. The method can be used for the study of related substances test of compound paracetamol and diphenhydramine hydrochloride tablets in the quality consistency evaluation. 

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