摘要
研制他唑巴坦杂质A国家标准物质,为提高国内他唑巴坦的质量控制标准提供依据。对他唑巴坦杂质A进行合成,利用红外、质谱、核磁共振波谱技术进行结构确认,并对杂质A进行含量均匀性检查和短期稳定性考察,再测定其水分和炽灼残渣含量,并以10 mmol/L醋酸铵溶液-乙腈(98∶2)为流动相的高相液相色谱法测定杂质A的纯度,应用质量平衡法确定首批他唑巴坦杂质A国家标准物质的含量,同时采用核磁共振波谱定量法测定其含量,与质量平衡法结果相互验证。结果发现,本研究所研制的他唑巴坦杂质A标准物质与《中华人民共和国药典:二部》(2015年版)他唑巴坦系统适用性溶液中最大降解杂质和USP41中收载的他唑巴坦有关物质A标准物质结构一致;在95%置信范围内,分装后杂质A的瓶间和瓶内方差之比为0.61(小于F0.05(11,12)),均匀性良好;杂质A中有机杂质含量为0.90%,水分含量为1.24%,无机杂质含量为0.25%,以质量平衡法确定杂质A含量为97.6%,与核磁共振波谱定量法结果97.1%基本一致;在25℃条件下,杂质A面积归一化纯度在0、3、5和10 d的均值均为99.1%,证明样品在室温下10 d内稳定。本研究首次制备了他唑巴坦杂质A国家标准物质。
To improve the standard of quality control of tazobactam and its preparations in China,national reference standard of tazobactam impurity A was developed.After tazobactam impurity A was synthesized,its structure was validated by infrared(IR),mass spectrometry(MS)and nuclear magnetic resonance(NMR),and its content uniformity and short-term stability were measured and investigated.Then,water content and residue on ignition of impurity A were determined,and its purity was determined using high performance liquid chromatography(HPLC)with 10 mmol/L ammonium acetate solution-acetonitrile(98∶2)as the mobile phase.Mass balance method was used to determine the content of the first batch of tazobactam impurity A national standard substance.Meanwhile,nuclear magnetic quantitative method was used to calculate the content,which was mutually verified with the mass balance method.The developed reference material of tazobactam impurity A is consistent with the maximum degradation impurity in tazobactam system applicability solution and the reference material of tazobactam related substance A contained in USP41.Within the 95%confidence range,the ratio of inter-and intra-bottle variance of impurity A after separation was 0.61(<F0.05(11,12)),proving that the uniformity was satisfying.The contents of organic impurity,water content and inorganic impurity in impurity A were 0.90%,1.24%and 0.25%,respectively.The content of impurity A was determined to be 97.6%by mass balance method,which was basically consistent with the result of nuclear magnetic quantitative method(97.1%).Under the condition of 25°C,the area normalized purity of impurity A was 99.1%at 0,3,5 and 10 days,proving that the sample was stable at room temperature for 10 days.Finally the first batch of national standard substance of tazobactam impurity A was established successfully.
作者
肖亭
王晨
田冶
张夏
刘颖
马步芳
刘书妤
姚尚辰
冯艳春
XIAO Ting;WANG Chen;TIAN Ye;ZHANG Xia;LIU Ying;MA Bufang;LIU Shuyu;YAO Shangchen;FENG Yanchun(National Institutes for Food and Drug Control,Beijing 102629;Shanghai University of Engineering Science,Shanghai 201620,China)
出处
《中国药科大学学报》
CAS
CSCD
北大核心
2021年第1期60-65,共6页
Journal of China Pharmaceutical University
基金
国家科技支撑计划资助项目(No.2015BAK45B01)。
关键词
他唑巴坦
他唑巴坦杂质A
杂质标准物质
结构确证
质量平衡法
赋值
tazobactam
tazobactam impurity A
national impurity reference standard
structural identification
mass balance method
content assignment
