Study on the Reaction Impurities Between Bromhexine Hydrochloride and Excipients in Bromhexine Hydrochloride Injection
10.13748/j.cnki.issn1007-7693.20223213
- VernacularTitle:盐酸溴己新注射液中溴己新与辅料反应杂质研究
- Author:
Zhili ZENG
1
,
2
;
Zhongli WU
2
;
Baolin LIU
2
;
Fei JIA
2
;
Jinfang LOU
2
;
Lushan YU
1
Author Information
1. Zhejiang University, Hangzhou 310058, China
2. Hangzhou Bio-Sincerity Pharma-Tech Co., Ltd., Hangzhou 311103, China
- Publication Type:Journal Article
- Keywords:
bromhexine hydrochloride;
impurities analysis;
unknown impurity;
LC-MS/MS
- From:
Chinese Journal of Modern Applied Pharmacy
2024;41(3):378-385
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE :To identify, synthesize and analyze the structure of unknown impurities unique to bromhexine hydrochloride injection and set the impurities as known impurity to control.
METHODS
The structure of unknown impurities was derived through two-dimensional liquid chromatography tandem mass spectrometry(2DLC-HRMS/MS), and the source of impurities was derived based on the product's prescription process. The mechanism of impurities generation was analyzed, and impurity monomers were obtained through directional synthesis. The structure of impurities was confirmed using techniques such as 2DLC-HRMS/MS and nuclear magnetic resonance. Finally, HPLC was used to verify the analysis method of impurities.
RESULTS
It was confirmed that such impurities were produced in a reaction between bromhexine and the excipient glucose. The correction factor of the two impurities were 2.2 and 2.4, the analytical method was specific and reproducible.
CONCLUSION
Name the two injection specific impurities as impurity 1 and impurity 2 respectively, and use them as known impurities to be included in the standard, calculate the impurity content using the self control and correction factor method. This study is of great significance in guiding the impurity control of bromhexine hydrochloride injection and the screening of excipient glucose.
