目的 制備以對(duì)乙酰氨基酚（PA）和氫溴酸右美沙芬（DX）為主成分的復(fù)方對(duì)乙酰氨基酚口服液，考察PA、DX與輔料間的相容性。方法 建立適合口服液中PA、DX含量測(cè)定和有關(guān)物質(zhì)檢查的高效液相色譜（HPLC）法，將PA和DX分別與輔料（甘油、丙二醇、山梨醇、三氯蔗糖、苯甲酸鈉、依地酸二鈉、黃原膠、色素、香精）按一定比例混合、加水溶解并調(diào)節(jié)pH值，制備二元相容性樣品，并取制劑、PA陰性制劑、DX陰性制劑，于高溫（60℃）和光照（4 500 lx）條件下破壞0、5、10 d，記錄溶液性狀、pH值；采用HPLC法檢測(cè)主成分和有關(guān)物質(zhì)含量變化。結(jié)果 建立的HPLC法專屬性好，線性關(guān)系良好（r＞0.999），回收率、精密度和耐用性等均符合要求。在光照條件下，除棕色PET瓶包裝復(fù)方對(duì)乙酰氨基酚口服液外，相容性樣品從木槿紫色變?yōu)樯钏{(lán)色。與0 d相比，樣品pH值逐漸增大，高溫條件下增加幅度整體高于光照條件；PA陰性制劑、DX陰性制劑和復(fù)方對(duì)乙酰氨基酚口服液，作為一個(gè)比較完整的制劑體系，pH值變化不明顯。光照條件下PA和DX的相容性樣品含量降低程度總體高于高溫條件；PA與依地酸二鈉、黃原膠和香精的相容性樣品含量降低幅度高于PA溶液；DX與苯甲酸鈉和依地酸二鈉的輔料相容性樣品含量降低幅度較高；輔料相容性樣品含量降低幅度均在2.5%以下。PA總雜質(zhì)最高達(dá)到1.3%，DX總雜質(zhì)最高達(dá)到2.25%，DX在高溫條件下穩(wěn)定性較高，在光照條件下穩(wěn)定性較差。結(jié)論 光照和pH值對(duì)主成分穩(wěn)定性影響較大，將主成分制備成具有一定pH值緩沖區(qū)間的制劑，并采用避光性較好的包裝材料能夠有效提高PA和DX的穩(wěn)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