目的 制备以对乙酰氨基酚（PA）和氢溴酸右美沙芬（DX）为主成分的复方对乙酰氨基酚口服液，考察PA、DX与辅料间的相容性。方法 建立适合口服液中PA、DX含量测定和有关物质检查的高效液相色谱（HPLC）法，将PA和DX分别与辅料（甘油、丙二醇、山梨醇、三氯蔗糖、苯甲酸钠、依地酸二钠、黄原胶、色素、香精）按一定比例混合、加水溶解并调节pH值，制备二元相容性样品，并取制剂、PA阴性制剂、DX阴性制剂，于高温（60℃）和光照（4 500 lx）条件下破坏0、5、10 d，记录溶液性状、pH值；采用HPLC法检测主成分和有关物质含量变化。结果 建立的HPLC法专属性好，线性关系良好（r＞0.999），回收率、精密度和耐用性等均符合要求。在光照条件下，除棕色PET瓶包装复方对乙酰氨基酚口服液外，相容性样品从木槿紫色变为深蓝色。与0 d相比，样品pH值逐渐增大，高温条件下增加幅度整体高于光照条件；PA阴性制剂、DX阴性制剂和复方对乙酰氨基酚口服液，作为一个比较完整的制剂体系，pH值变化不明显。光照条件下PA和DX的相容性样品含量降低程度总体高于高温条件；PA与依地酸二钠、黄原胶和香精的相容性样品含量降低幅度高于PA溶液；DX与苯甲酸钠和依地酸二钠的辅料相容性样品含量降低幅度较高；辅料相容性样品含量降低幅度均在2.5%以下。PA总杂质最高达到1.3%，DX总杂质最高达到2.25%，DX在高温条件下稳定性较高，在光照条件下稳定性较差。结论 光照和pH值对主成分稳定性影响较大，将主成分制备成具有一定pH值缓冲区间的制剂，并采用避光性较好的包装材料能够有效提高PA和DX的稳定性。

Objective To establish a high performance liquid chromatography (HPLC) for compound acetaminophen oral liquid assay and the related substances .To investigate the compatibility of acetaminophen and dextromethorphan hydrobromide with common excipients of oral liquid. Methods Mixed acetaminophen and dextromethorphan hydrobromide with single excipient (glycerol, propylene glycol, sorbitol, sucralose, sodium benzoate, disodium ediate, xanthan gum, pigment, essence) respectively in a certain proportion, the mixtures were dissolved by water,and the pH value were adjusted to suitable level, treated the mixtures under the conditions of high temperature (60 ℃ ) and light (4 500 lx) for 0, 5 and 10 days. The changes of solutions properties, pH value, content and related substances were recorded. The content and related substances in the samples were determined by the established HPLC method. Results The method had good specificity and good linear relationship (r > 0.998),the average recovery precision and durability meet the requirements. Under the light condition, except for the brown PET bottle packaging compound acetaminophen oral solution, color of the compatibility samples change from hibiscus purple to dark blue. Compared with 0 d, the pH value of samples increased gradually, and the increase rate under high temperature was higher than that under light condition. The pH value of PA negative preparation, DX negative preparation and compound acetaminophen oral solution, as a relatively complete preparation system, did not change significantly. The reduction degree of the compatibility of PA and DX samples under light condition was higher than that under high temperature condition. The compatibility of PA with disodium ediate, xanthan gum and essence decreased more than that of PA solution. The excipient compatibility of DX with sodium benzoate and disodium ediate decreased significantly. The reduction range of excipient compatibility samples was less than 2.5%. The total impurities of acetaminophen and dextromethorphan hydrobromide reached 1.3% and 2.25% respectively. DX was more stable under high temperature and less stable under light. Conclusion Light and the solution's pH value had great influence on the stability of the principal components.The stability of acetaminophen and dextromethorphan hydrobromide can be effectively improved by preparing the solution into a certain pH value buffer and using light shielding packaging.

R944.1