基于LC-MS/MS技术的妥布霉素地塞米松滴眼液体外评价的分析方法研究  

Analysis Method for In Vitro Evaluation of Tobramycin and Dexamethasone Eye Drops Based on LC-MS/MS

作　　者：陈爽 刘小勤 郑小玲 石云峰 朱价 罗英 刘柱 CHEN Shuang;LIU Xiaoqin;ZHENG Xiaoling;SHI Yunfeng;ZHU Jia;LUO Ying;LIU Zhu(Zhejiang Institute for Food and Drug Control,Hangzhou 310014,China;NMPA Key Laboratory for Core Technology of Generic Drug Evaluation,Hangzhou 310014,China)

机构地区：[1]浙江省食品药品检验研究院,杭州310014 [2]国家药品监督管理局仿制药评价关键技术重点实验室,杭州310014

出　　处：《中国药学杂志》2025年第6期646-651,共6页Chinese Pharmaceutical Journal

基　　金：浙江省药品监管系统科技计划项目资助(2024016,2022001)。

摘　　要：目的建立液相色谱-串联质谱联用(LC-MS/MS)法同时测定人工泪液中妥布霉素和地塞米松的浓度,用于妥布霉素地塞米松滴眼液体外释放试验的研究中妥布霉素和地塞米松浓度的检测。方法采用Agilent Zorbax Eclipse plus-C_(8)色谱柱,以2 mmol·L^(-1)乙酸铵水溶液为流动相A,体积分数90%甲醇水溶液为流动相B,梯度洗脱,流速0.5 mL·min^(-1),柱温40℃,进样体积2μL;采用质谱检测器,电喷雾离子源(ESI)离子化方式,多重反应监测(MRM)模式,正离子模式。结果妥布霉素、地塞米松均在200~5000 ng·mL^(-1)内线性良好,定量下限均为200 ng·mL^(-1)。妥布霉素、地塞米松在样品处理后放置进样器48 h条件下稳定性良好。结论本研究建立的方法快速、高效、准确、灵敏,可用于妥布霉素地塞米松滴眼液在人工泪液中的药物浓度检测和体外释放试验的研究。OBJECTIVE To establish a liquid chromatography-tandem mass spectrometry(LC-MS/MS)method for simultaneous determination of tobramycin and dexamethasone in artificial tears,and detect drug use concentration in human tears and in vitro release.METHODS Zorbax Eclipse plus-C_(8) column was used with 2 mmol·L^(-1)ammonium acetate aqueous solution as mobile phase A and 90%methanol aqueous solution as mobile phase B for gradient elution.The flow rate was 0.5 mL·min^(-1),the column temperature was maintained at 40℃,and the injection volume was 2μL.A mass spectrometer was used with ESI ionization mode,MRM mode,and positive ion mode.RESULTS Tobramycin and dexamethasone showed good linearity in the concentration range of 200-5000 ng·mL^(-1),and the lower limit of quantification was 200 ng·mL^(-1).CONCLUSION The established method is rapid,efficient,accurate and sensitive,and can be used for the detection of drug concentration in tears and in vitro release test of tobramycin and dexamethasone eye drops.

关 键 词：液相色谱-串联质谱联用 体外评价 人工泪液 妥布霉素 地塞米松 

分 类 号：R917[医药卫生—药物分析学]