复方醋酸地塞米松制剂中9种抑菌剂含量测定方法的建立及评价

Establishment and Evaluation of Determination Methods of Nine Antimicrobial Agents in Compound Dexamethasone Acetate

目的建立HPLC同时测定复方醋酸地塞米松乳膏、凝胶中可能含有的9种常见抑菌剂的方法。对2018年国家药品抽验到的国内44个生产厂家的样品进行检测及评价。方法采用Waters Xbridge Shield RP18色谱柱(4.6 mm×250 mm,5μm);以1%三乙胺溶液(加磷酸调节pH至3.0)为流动相A,乙腈为流动相B,进行梯度洗脱;检测波长215 nm。采用该方法对国内样品进行检测,并对该复方制剂中抑菌剂使用进行有效性和安全性评价。结果在该色谱条件下,9种抑菌剂分离良好,在1~70μg·mL^(−1)内线性关系良好,平均回收率为91.2%~100.4%,RSD为0.1%~6.7%。样品中共检测出布罗波尔、羟苯甲酯、羟苯乙酯、羟苯丙酯和苯扎溴铵5种抑菌剂,抑菌剂浓度为0.48~2.89 mg·g^(−1)。结论样品中存在抑菌剂使用不规范现象。本研究可为该品种中抑菌剂的规范使用提供技术支持。

OBJECTIVE To establish an HPLC method for the simultaneous determination of 9 common antimicrobial agents in compound dexamethasone acetate cream and gel.The samples from 44 domestic manufacturers that were sampled and inspected by the national drug in 2018 were tested and evaluated.METHODS Waters Xbridge Shield RP18 column(4.6 mm×250 mm,5μm)was used,1%triethylamine solution(pH adjusted to 3.0 by phosphoric acid)(mobile phase A)and acetonitrile(mobile phase B)were used for gradient elution,and the detection wavelength was 215 nm.The method was used to detect the samples in domestic,and to evaluate the effectiveness and safety of the antibacterial agent in the compound preparation.RESULTS Under this chromatographic condition,9 kinds of bacteriostatic agents were separated well,the linear relationships were good in the range of 1−70μg·mL^(−1),the average recoveries were 91.2%−100.4%,and the RSDs were 0.1%−6.7%.Five bacteriostatic agents,namely bropol,methylparaben,ethylparaben,propyl 4-hydroxybenzoate and benzalkonium bromide,were detected in the samples,and the concentration of the antimicrobial agents ranged from 0.48−2.89 mg·g^(−1).CONCLUSION There are some irregularities in the use of antimicrobial agents in the samples.This study can provide technical support for the standardized use of antimicrobial agents in this variety.