马来酸噻吗洛尔滴眼液中抑菌剂的质量控制

Quality Control of Bacterial Inhibitor in Timolol Maleate Eye Drops

目的:建立同时对马来酸噻吗洛尔滴眼液中常用的7种抑菌剂的定性分析、4种抑菌剂的定量测定方法,以筛查该滴眼液中所含抑菌剂的种类与含量是否与处方标注内容一致。方法:样品来自15家生产企业的85批马来酸噻吗洛尔滴眼液。以保留时间和二极管阵列检测器(DAD)光谱图作为定性依据,采用高效液相色谱(HPLC)-DAD法同时对各样品中的7种抑菌剂(山梨酸、硫柳汞、羟苯甲酯、羟苯乙酯、羟苯丙酯、羟苯丁酯、苯扎溴铵)进行定性分析;采用HPLC法同时定量测定样品中的羟苯乙酯与苯扎溴铵,采用原子荧光光谱法同时定量测定样品中的硫柳汞和醋酸苯汞。结果:定性分析结果表明,85批样品所含抑菌剂的种类均与处方标注的一致;定量测定结果表明,抑菌剂含量以处方量的±20%为限度计,样品不合格率为15.2%,企业不合格率为53.8%。结论:所建立的方法适用于马来酸噻吗洛尔滴眼液中抑菌剂的质量控制。建议在马来酸噻吗洛尔滴眼液的质量标准中设置抑菌剂的含量检查项。

OBJECTIVE： To establish a method for quantitative analysis of 7 kinds of bacterial inhibitors and quantitative deter- mination of 4 kinds of bacterial inhibitors to check whether the types and content of bacterial inhibitors in Timolol maleate eye drops （TMED） are in agreement with the formulation. METHODS： The samples were 85 batches of TMED from 15 manufacturers. With the qualitative basis of retention time and diode array detector （DAD） spectrum, HPLC-DAD method was adopted for qualita- tive analysis of 7 kinds of bacterial inhibitors in samples, such as sorbic acid, thiomersalate, methylparaben, ethylparaben, propyl- paraben, butylparaben and benzalkonium bromide. HPLC method was also conducted for quantitative determination of ethylparaben and benzalkonium bromide of samples, and atomic fluorescence spectrometry （AFS） was detected for thiomersalate and phenylmer- curic acetate of samples. RESULTS： The qualitative analysis results showed that the types of bacterial inhibitors in 85 batches of TMED were all in agreement with the formulation. The quantitative determination results showed that the bacterial inhibitors content in± 20% of formulation was limit gauge. The unqualified rate of the samples and enterprises were 15.2% and 53.8%, respective- ly. CONCLUSIONS ： The developed method is suitable for the quality control of the bacterial inhibitors in TMED. It is suggested that set content check of bacterial inhibitors in the quality standard of TMED.