依诺沙星滴眼液抑菌剂考察

Investigation of Preservatives in Enoxacin Eye Drops

关键词:  依诺沙星滴眼液  硫柳汞  羟苯乙酯  苯扎溴铵  含量测定  稳定性

Key words:  enoxacin eye drops  merthiolate  ethylparaben  benzalkonium bromide  determination  stability

摘要:

目的 建立测定依诺沙星滴眼液中抑菌剂硫柳汞、羟苯乙酯和苯扎溴铵的HPLC含量测定方法，并对这3种抑菌剂的稳定性进行考察。方法 选用C₁₈柱，以1%三乙胺溶液（用磷酸调节pH值至3.0）为流动相A，以甲醇为流动相B，进行梯度洗脱；检测波长苯扎溴铵为218 nm，羟苯乙酯和硫柳汞为262 nm，进样量为20 μL。同时考察抑菌剂的稳定性。结果 羟苯乙酯、硫柳汞和苯扎溴铵之间的分离度分别为19.7，48.7。硫柳汞在9.1~151.4 μg·mL^-1、羟苯乙酯在2.1~41.2 μg·mL^-1、苯扎溴铵在21.8~218.0 μg·mL^-1内均呈现良好的线性关系（r=0.999，1.000，0.999），其检出限分别为1.4，1.2，13.1 ng。在高温条件下，硫柳汞和羟苯乙酯含量均略有下降；在紫外光照条件下，硫柳汞含量下降明显；苯扎溴铵几乎不受高温和紫外光照的影响。结论 该方法灵敏度高，能够有效评估滴眼液中抑菌剂的含量。

Abstract:

OBJECTIVE To establish a method for the determination of merthiolate, ethylparaben and benzalkonium bromide in enoxacin eye drops by HPLC, and to investigate the stability of these three preservatives. METHODS The analysis was performed on C₁₈ column, 1% triethylamine (adjusted to pH 3.0 with phosphoric acid) served as mobile phase A, methanol as mobile phase B by gradient elution. The detection wavelength was 218 nm (benzalkonium bromide) and 262 nm (merthiolate and ethylparaben) with the injection volume of 20 μL. The stability of preservatives was investigated. RESULTS The resolution between ethylparaben, merthiolate and benzalkonium bromide was 19.7 and 48.7. The standard curves of merthiolate, ethylparaben and benzalkonium bromide were linear in the range of 9.1-151.4 μg·mL^-1, 2.1-41.2 μg·mL^-1 and 21.8-218.0 μg·mL^-1 (r=0.999, 1.000, 0.999). The limit of detection were 1.4, 1.2, 13.1 ng. The content of merthiolate and ethylparaben decreased lightly under high temperature condition. Merthiolate decreased obviously under UV irradiation condition. Benzalkonium bromide was almost impervious to high temperature and UV irradiation conditions. CONCLUSION The method has high sensitivity and can effectively evaluate the content of preservatives in eye drops.