基于析因设计优化复方乙酸曲安奈德洗剂中药物的稳定性

Simultaneous determination of three drug contents in compound triamcinolone acetonide lotion and improvement of drug stability by factorial design

目的建立同步测定复方乙酸曲安奈德洗剂(简称复方TAA洗剂)中乙酸曲安奈德(TAA)、氯霉素(LMS)、水杨酸(SAL)质量分数的HPLC法;并通过析因设计研究影响药物稳定性的重要因素并优化处方。方法采用Waters SunFire^(TM)C_(18)柱(4.6 mm×150 mm,5μm),流动相为0.1%磷酸水溶液-甲醇(体积比40∶60),流速为1.0 mL/min,进样量为10μL,检测波长为254 nm,柱温为30℃。以制剂在高温(60℃,10 d)条件下药物降解程度为指标,采用析因设计研究pH值、抗氧剂、NaCl的影响,分析最重要的影响因素并进行优化。结果 TAA、LMS、SAL分别在2.5~15、25~150、60~360μg/mL线性范围良好,平均回收率分别为(100.7±1.7)%、(100.6±1.7)%、(100.2±1.2)%。通过析因设计,确定pH值为洗剂关键影响因素,处方最佳pH为4.5,抗氧剂和Na Cl对药物稳定性几乎无影响。结论建立的同步测定复方TAA洗剂中3种药物的HPLC方法重复性好,通过控制洗剂的pH值可以得到稳定性较好的洗剂。

Objective To establish an HPLC method for simultaneous determination of the content of triamcinolone acetonide acetate,chloramphenicol and salicylic acid in lotion. The factorial design was used to optimize the prescription in order to improve the drug stability. Methods Waters SunFire^（TM）C_（18） column（ 4.6 mm× 150 mm,5 μm） was used,the mobile phase consisted of 0.1% phosphoric acid aqueous solutionmethanol（ 40 ∶60） with the flow rate of 1.0 mL/min,the sample volume of 10 μL,the detection wavelength of 254 nm and the column temperature of 30 ℃. The degree of drug degradation under high temperature（ 60 ℃,10 days） was taken as the index. The factorial design was used to study the effect of the pH,antioxidant and Na Cl on the stability of the preparation to optimize the prescription. Results The linear range of triamcinolone acetonide acetate, chloramphenicol and salicylic acid was 2. 5-15, 25-150 and60-360 μg/mL respectively. The average recovery was（ 100.7±1.7） %,（ 100.6±1.7） % and（ 100.2± 1.2） %,respectively. The factor of pH was determined,and the best pH was 4. 5. Conclusion The HPLC method established can be used for simultaneous determination of three drugs in lotion, and the compound triamcinolone acetonide acetate lotion with good stability was obtained by controlling the pH of the lotion.