2. Academic Validation
  3. Quantitative analysis of impurities in leucomycin bulk drugs and tablets: A high performance liquid chromatography-charged aerosol detection method and its conversion to ultraviolet detection method

Quantitative analysis of impurities in leucomycin bulk drugs and tablets: A high performance liquid chromatography-charged aerosol detection method and its conversion to ultraviolet detection method

  • J Pharm Biomed Anal. 2021 Aug 5:202:114148. doi: 10.1016/j.jpba.2021.114148.
Guijun Liu 1,  Bingqi Zhu 2,  Fan Wang 3,  Xiaojuan Ren 1,  Yasheng Li 1,  Fengmei Zhang 4,  Jian Wang 5
Affiliations

Affiliations

  • 1 Green Pharmaceutical Collaborative Innovation Center of Yangtze River Delta region, Zhejiang University of Technology, Hangzhou, 310014, China.
  • 2 Zhejiang Chinese Medical University, Hangzhou, 310053, China.
  • 3 School of Medicine, Zhejiang University, Hangzhou, 310058, China.
  • 4 Key Laboratory for Core Technology of Generic Drug Evaluation National Medical Product Administration, Zhejiang Institute for Food and Drug Control, Hangzhou, 310052, China.
  • 5 Green Pharmaceutical Collaborative Innovation Center of Yangtze River Delta region, Zhejiang University of Technology, Hangzhou, 310014, China; Key Laboratory for Core Technology of Generic Drug Evaluation National Medical Product Administration, Zhejiang Institute for Food and Drug Control, Hangzhou, 310052, China. Electronic address: wangjianhw2000@163.com.
PMID: 34052548 DOI: 10.1016/j.jpba.2021.114148
Abstract

Toxic impurities were found in leucomycin and its preparation, however the content determination of impurities was challengeable due to the lacking of their Reference Standards. In this study, we developed high-performance liquid chromatography method coupled with charged aerosol detection (CAD) for the quantification of related substance of leucomycin (kitasamycin) bulk drugs and tablets, however, the CAD was not yet popular. In order to carry out quantitation work conveniently in the laboratory without CAD instruments, a high-performance liquid chromatography method coupled with ultraviolet (UV) detection was developed with the assistant of the HPLC-CAD results. The relative response of impurities on CAD chromatogram was used for guiding the establishment of HPLC-UV method, which could achieve the quantitation task in the absence of impurity Reference Standards. The developed HPLC-UV method was validated according to the ICH guideline and showed good precision, reproducibility and linearity with determination coefficient higher than 0.9999. The limit of detection and quantitation were 0.3 and 0.5 μg mL-1, respectively. The recoveries were 92.9 %-101.5 % at the spiked concentration levels of 0.1 %, 0.8 %, 1.0 and 1.2 % with relative standard deviations (RSDs, n = 3) lower than 2.0 %. Finally, the developed HPLC-CAD and -UV methods were compared by the determination of impurities in several batches of leucomycin bulk drugs and tablets. The results demonstrated that the developed HPLC-UV method was simple and reliable. This study developed methods to quantify the related substance in leucomycin and tablets, and discussed a strategy of the conversion of HPLC-CAD method to HPLC-UV method. The developed methods could be considered for implementation into pharmacopeial monographs in the future.

Keywords

Charged aerosol detection; Kitasamycin; Leucomycin; Quantitative; Ultraviolet detection.

Figures
Products