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ZHOU Yu, NI Weixing, LIU Yong, HUANG Pengfei, SU Mengxiang. Determination of potential genotoxic impurities chloroacetyl chloride and chloroacetic acid in azintamide raw material[J]. Journal of China Pharmaceutical University, 2022, 53(3): 300-305. DOI: 10.11665/j.issn.1000-5048.20220307
Citation: ZHOU Yu, NI Weixing, LIU Yong, HUANG Pengfei, SU Mengxiang. Determination of potential genotoxic impurities chloroacetyl chloride and chloroacetic acid in azintamide raw material[J]. Journal of China Pharmaceutical University, 2022, 53(3): 300-305. DOI: 10.11665/j.issn.1000-5048.20220307
shu

Determination of potential genotoxic impurities chloroacetyl chloride and chloroacetic acid in azintamide raw material

  • 1.

    School of Pharmacy, China Pharmaceutical University, Nanjing 210009

  • 2.

    Yangzhou Yiyang Pharmaceutical Co., Ltd., Yangzhou 225600

  • 3.

    Ministry of Education Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Nanjing 210009

  • 4.

    National Medical Products Administration (NMPA) Key Laboratory for Research and Evaluation of Pharmaceutical Preparations and Excipients, Nanjing 210009, China

Funds: This study was supported by the National Natural Science Foundation of China (No.81872833)
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  • Received Date: January 25, 2022
  • Revised Date: April 26, 2022
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    • 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.
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