Establishment of national reference standard of tazobactam impurity A
10.11665/j.issn.1000-5048.20210108
- VernacularTitle:他唑巴坦杂质A国家标准物质的研制
- Author:
Ting XIAO
1
;
Chen WANG
;
Ye TIAN
;
Xia ZHANG
;
Ying LIU
;
Bufang MA
;
Shuyu LIU
;
Shangchen YAO
;
Yanchun FENG
Author Information
1. 中国食品药品检定研究院
- Publication Type:Journal Article
- Keywords:
tazobactam;
tazobactam impurity A;
national impurity reference standard;
structural identification;
mass balance method;
content determination
- From:
Journal of China Pharmaceutical University
2021;52(1):60-65
- CountryChina
- Language:Chinese
-
Abstract:
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.
