HPLC-DAD法同时测定注射用头孢他啶阿维巴坦钠复方制剂的含量  

Simultaneous determination of compound preparation of ceftazidime-acibactam for injection by HPLC-DAD

作　　者：王琰[1] 姚尚辰[1] 张培培[1] 邹文博[1] 李进[1] 许明哲[1] 胡昌勤[1] WANG Yan;YAO Shang-chen;ZHANG Pei-pei;ZOU Wen-bo;LI Jin;XU Ming-zhe;HU Chang-qin(National Institutes for Food and Drug Control, Beijing 102629 , China)

机构地区：[1]中国食品药品检定研究院,北京102629

出　　处：《中国新药杂志》2019年第5期541-546,共6页Chinese Journal of New Drugs

基　　金：国家"重大新药创制"科技重大专项资助项目(2015ZX09303001);北京市科技计划课题资助项目(Z151100000115013);国家科技支撑项目(2015BAK45B00)

摘　　要：目的:首次建立一种HPLC-DAD法用于测定新型抗菌药物复方制剂———注射用头孢他啶阿维巴坦钠中2个组分的含量。方法:采用Kromasil C_(18)(250 mm×4.6 mm,5μm)为色谱柱;流动相A为30mmol·L^(-1)磷酸氢二钠-20 mmol·L^(-1)磷酸二氢钾缓冲液,流动相B为30 mmol·L^(-1)磷酸氢二钠和20 mmol·L^(-1)磷酸二氢钾的缓冲液-乙腈(50∶50),流动相A-流动相B(85∶15);流速为1.0 m L·min^(-1);柱温为40℃;检测波长为200 nm;进样量为10μL。结果:头孢他啶和阿维巴坦分别在0.005～1.0 mg·m L^(-1)(r=0.999 9)和0.006～1.0 mg·m L^(-1)(r=0.999 9)的浓度范围内线性关系良好。头孢他啶和阿维巴坦的平均加样回收率分别为99.2%(RSD=1.2%,n=3)和98.7%(RSD=3.1%,n=3),检测限分别为2μg·m L^(-1)和1μg·m L^(-1),两者的日内和日间精密度均小于1.5%。注射用头孢他啶阿维巴坦钠是由头孢他啶、阿维巴坦和碳酸钠组成的混合物,由于特殊灌装工艺及物理性质上的差异会造成三者在样品瓶中分布不均匀,建议采用整瓶稀释法测定该抗菌药物复方制剂的含量。结论:本研究建立的注射用头孢他啶阿维巴坦钠含量测定方法快速准确且重现性好,可用于常规质控实验室的日常检定。Objective:To develop an HPLC coupled with diode array detection(DAD)method for the simultaneous determination of new antibiotic combination ceftazidime and avibactam for injection.Methods:The column was Kromasil C18(250 mm×4.6 mm,5μm).The mobile phase A was phosphate buffer containing 30mmol·L^-1disodium hydrogen phosphate and 20 mmol·L^-1potassium dihydrogen phosphate,the mobile phase B was phosphate buffer(30 mmol·L^-1disodium hydrogen phosphate and 20 mmol·L^-1potassium dihydrogen phosphate)and acetonitrile(50∶50).The ratio of mobile phases A and B was 85∶15 at a flow rate of 1.0 m L·min^-1.The column temperature was 40℃.The detection wavelength was 200 nm.The injection volume was10μL.Results:Ceftazidime and avibactam have good linear relation in the concentration range of 0.005~1.0mg·m L^-1(r=0.999 9)and 0.006~1.0 mg·m L^-1(r=0.999 9),respectively.The recovery rates of ceftazidime and avibactam were 99.2%(RSD=1.2%,n=3)and 98.7%(RSD=3.1%,n=3),respectively.The limits of detection(LODs)of ceftazidime and avibactam were 2μg·m L-1and 1μg·m L^-1,respectively.The RSD of intra-and inter-day was less than 1.5%.Ceftazidime and avibactam for injection is composed of ceftazidime,avibactam and sodium carbonate.The special filling process and different physical properties could cause misdistribution of the three components in the injection bottle.Therefore,a whole bottle dilution method was proposed for the determination of the antibiotic combination.Conclusion:The HPLC-DAD method of determination of ceftazidime and avibactam for injection developed in this study was fast,accurate and reproducible,which could be employed for daily identification in the routine quality control laboratory.

关 键 词：抗菌药物 复方制剂 头孢他啶 阿维巴坦 高效液相色谱法 含量测定 

分 类 号：R917[医药卫生—药物分析学]