Determination of potential genotoxic impurities chloroacetyl chloride and chloroacetic acid in azintamide raw material
10.11665/j.issn.1000-5048.20220307
- VernacularTitle:阿嗪米特原料药中潜在基因毒性杂质氯乙酰氯和氯乙酸的含量测定
- Author:
Yu ZHOU
1
;
Weixing NI
;
Yong LIU
;
Pengfei HUANG
;
Mengxiang SU
Author Information
1. 中国药科大学药学院
- Publication Type:Journal Article
- Keywords:
azintamide;
genotoxic impurity;
HPLC;
pre-column derivatization;
chloroacetyl chloride;
chloroacetic acid
- From:
Journal of China Pharmaceutical University
2022;53(3):300-305
- CountryChina
- Language:Chinese
-
Abstract:
In this paper, chemical derivatization-high performance liquid chromatography was used to determine the potential genotoxic impurities chloroacetyl chloride and chloroacetic acid, respectively, in the raw material of azintamide.Derivatization was carried out using 2-nitrophenylhydrazine followed by the determination.Separation was performed on a Thermo Syncronis C18 column (250 mm × 4.6 mm, 5 μm), with mobile phase consisting of 0.1% phosphoric acid in water (A) and acetonitrile(B) by gradient elution, at a flow rate of 1 mL/min.The column temperature was 40 °C and the detection wavelength was 226 nm.The blank solvent, derivatization reagent, and azintamide did not interfere with the peak of the test substance, and the target component was well separated from the others.For impurities chloroacetyl chloride and chloroacetic acid, the limits of detection (LOD) were 7.5 ng/mL and 15 ng/mL respectively. There was a good linear relationship between the integral area and the concentration in the range of 30-300 ng/mL.The sample recovery rate was in the range of 87.37% ~ 109.75%.The two methods established in this study have good specificity, good precision, high sensitivity and simple operation, which can be used for the trace determination of potential genotoxic impurities chloroacetyl chloride and chloroacetic acid in the raw material of azintamide.
