眼氨肽滴眼液中抑菌剂的含量测定及活性炭对抑菌剂的吸附性研究
Content determination of bacteriostats in ocular extractives eye drops and the absorption effect of activated carbon on it
-
摘要: 建立一种检测眼氨肽滴眼液中抑菌剂含量的HPLC法，使用Diamonsil C18(4.6 mm×250 mm，5 μm)色谱柱，以1%三乙胺溶液(用磷酸调节pH至 3.0)为流动相A，甲醇为流动相B进行梯度洗脱，检测波长为256 nm，柱温40 ℃，流速1.0 mL/min。在该条件下羟苯甲酯、羟苯乙酯和醋酸氯己定3种抑菌剂分离度良好，各抑菌剂在0.1~80 μg/mL质量浓度范围内，峰面积与浓度呈良好线性关系(r>；0.999 1)，回收率分别为97.2%~104.1%，RSD为0.8%~1.2%。用该法检测的5批市售眼氨肽滴眼剂抑菌剂含量均低于处方量的10%，经考察发现生产工艺中使用的活性炭对于抑菌剂有强吸附作用，温度越低、活性炭浓度越高对抑菌剂的吸附越强，其中活性炭对不同抑菌剂的吸附能力由大到小分别为:醋酸氯己定、羟苯乙酯、羟苯甲酯。结果表明，建立的HPLC法，操作简便，灵敏度高，重复性好，可用于快速准确测定眼氨肽滴眼液中抑菌剂含量；此外，本研究首次揭示了眼氨肽滴眼液生产中除杂工序对抑菌剂的影响，结果表明，在除杂质工序中，不适宜在添加尼泊金酯类和醋酸氯己定抑菌剂前使用活性炭除杂质，为其生产质量监控与提升提供了新的指导方案。Abstract: To establish a high performance liquid chromatography(HPLC)method to determine the content of bacteriostats in the ocular extractives eye drops, Diamonsil C18(4. 6 mm×250 mm, 5 μm)column was used, with gradient elusion by 1% triethylamine solution(pH 3. 0)(mobile phase A)and methanol(mobile phase B). The detection wavelength was 256 nm; the column temperature was 40 °C; and the flow rate was 1. 0 mL/min. Under these conditions, the three bacteriostats of methylparaben, ethylparoben and chlorhexidine acetate showed good resolution. The bacteriostats exhibited good linear relationship between the peak area and the concentration in the concentration range of 0. 1- 80 μg/mL(r> 0. 999 1). The recoveries were from 97. 2% to 104. 1%, and the RSD was 0. 8% to 1. 2%. The content of bacteriostats in all the five batches of ocular extractives eye drops was less than 10% of the prescription amount. It was found that the activated carbon used in the production process had strong adsorption effect on the bacteriostat, and that the lower the temperature and the higher the concentration of activated carbon, the stronger the adsorption of bacteriostatic agent. The adsorption capacity of activated carbon for different bacteriostats is: chlorhexidine acetate > ethylparoben > methylparaben. The results showed that the established HPLC method was easy to operate with high sensitivity and good repeatability. It can be used to determine the content of bacteriostat in ocular extractives eye drops quickly and accurately. In addition, this study reveals for the first time the effect of impurity removal process on bacteriostat in the production of ocular extractives eye drops. It is not suitable to use activated carbon to remove impurities before adding parabens and chlorhexidine acetate bacteriostats. The current work provides a new guiding basis for the monitoring and improvement of the quality of ocular extractives eye drops.
-
-
[1] Sun X.Clinical observation of ocular extractives eye drops combined with tropicamide in the treatment of pseudomyopia[J].Chin J Mod Drug Appl(中国现代药物应用),2011,3(5):124-125. [2] Li JQ.Therapeutic effect of ocular extractives eye drops on non-suppurative keratitis[J].J Mudanjiang Med Coll(牡丹江医学院学报),2003,24(1):24-25. [3] Xing F,Guo HY,Zhang YQ.Clinical observation of ocular extractives eye drops in the treatment of corneal epithelial persistent defects[J].Chin Ophthal Res(眼科研究),2003,21(2):212. [4] Wang J,Yang MS.Therapeutic effect of ocular extractives combined with recombinant human epidermal growth factor derivative eye drops on persistent epithelial defects[J].China Pract Med(中国实用医药),2008,3(25):127. [5] Zhang HZ,Yin WW,Chen M.Clinical research of vitamin a and ocular extractives eye drops ultrasonic spray inhalation in treatment of dry eye disease[J].J Med Forum(医药论坛杂志),2011,32(11):49-50. [6] Li F,Chen Y.Germicidal effects of the chlorhexidine acetate[J].J Microbiol(微生物学杂志),2014,34(1):101-103. [7] Chen X,Liu MX.Progress in research and application of preservatives in ophthalmic preparations[J].Tianjin Pharm(天津药学),2013,25(5):54-59. [8] An Y.Application and quality control of bacteriostatic agents in ophthalmic preparations[J].Tianjin Pharm(天津药学),2011,23(1):56-58. [9] Liu AM,Li W,Wang BM.Ocular surface damage of bacteriostatic agents in ophthalmic preparations[J].Chin Hosp Pharm J(中国医院药学杂志),2002,22(6):371-373. [10] Zhou CD,Huang ZS.Determination of chlorhexidine acetate in ocular extractives eye drops by HPLC[J].Tianjin Pharm(天津药学),2013. 25(2):15-17. [11] Chinese Pharmacopoeia Commission.Determination of bacteriostatic agent content in eye drops[EB/OL].(2018-03-28)[2018-09-06] .http://www.chp.org.cn/upload/userfiles/20180328/1101522202450037.pdf. [12] Dai X.Methods for improving clarity of ocular extraction injection[J].Chin J Biochem Pharm(中国生化药物杂志),2002,23(3):155-156. -
期刊类型引用(8)
1. 龚蕾蕾. 纳米药物递送系统治疗乳腺癌的研究进展. 医学理论与实践. 2023(06): 939-941 . 
百度学术
2. 卓新雨，张艾立，马菲，崔志磊，刘臻，谢恬. 纳米载药系统的研究进展. 广东化工. 2022(10): 85-87 . 百度学术
3. 刘盼，王路，董能峰，刘力，李炳生. 量子点的制备及其在药物检测和药物递送领域中的应用. 广东化工. 2021(08): 152-153+151 . 百度学术
4. 文鹏，石峰. 纳米材料在肿瘤治疗中的研究进展. 肿瘤药学. 2021(02): 153-157+164 . 百度学术
5. 程晓昆，张越，吕海军，刘歆颖，侯森林，陈爱兵. 多孔碳纳米材料构建抗肿瘤药物靶向传递系统的研究进展. 无机材料学报. 2021(01): 9-24 . 百度学术
6. 王小宁，闫梦茹，马远涛，梁晓燕，罗国平. 载紫杉醇聚(2-乙基-2-噁唑啉)修饰单壁碳纳米管递药系统的制备及体外抗肿瘤作用评价. 中草药. 2020(03): 607-615 . 百度学术
7. 王鹏. 基于碳纳米线圈的细胞应激性测试探针. 云南大学学报(自然科学版). 2020(05): 941-948 . 百度学术
8. 李学暖，李天昊，张嘉琳，黎孔月，蒋靖超，程昊. 多壁碳纳米管修饰玻碳电极电致化学发光测奈福泮. 广西科技大学学报. 2020(04): 124-131 . 百度学术
其他类型引用(8)
计量
- 文章访问数: 280
- HTML全文浏览量: 17
- PDF下载量: 812
- 被引次数: 16
下载:
