Method for detecting content of isomer impurities in sitafloxacin

Abstract

The invention discloses a method for detecting the content of isomer impurities in sitafloxacin. The method comprises respectively preparing control solutions of isomers and sitafloxacin and a test sample solution, respectively detecting the control solutions and the test sample solution through a capillary electrophoresis method, and calculating contents of isomer impurities through an external standard method according to a peak area or a standard curve of the peak area and the concentration. The method has the advantages of low cost, simple processes, high resolution degree, good flexibility, good linearity, specificity, precision, stability, sensitivity, repeatability, high sample recovery rate and accurate and reliable detection result. The method realizes simultaneous separation of sitafloxacin and its isomers such as IMA, IMB, IMC, IMD and IME, provides an effective method for sitafloxacin product quality monitoring and has a practical value.

Description

technical field [0001] The invention relates to a method for detecting the content of isomer impurities in sitafloxacin, belonging to the technical field of chemical analysis. Background technique [0002] It is well known in the art that the impurities in the drug are the main factors affecting the purity of the drug. If the impurities contained in the drug exceed the limit requirements specified in the quality standards, it is very likely to cause changes in the appearance, shape and physical and chemical parameters of the drug, and even affect the stability of the drug. , will lead to decreased drug activity and increased toxic and side effects, seriously endangering the product quality of the drug and the drug safety of patients; at the same time, the impurities in the drug cover a very wide range, not only including impurities with different molecular formulas in the conventional sense, but for chiral drugs , including impurities of drug isomers; more than 80% of the dr...

AI Technical Summary

Problems solved by technology

[0011] At present, the analysis method of sitafloxacin isomers mainly adopts HPLC chiral analysis method. For example, Zhang Qiujia et al. used octadecylsilane bonded silica gel column as chromatographic column, and selected D-phenylalanine as chiral additive. Copper sulfate is used as a coordination metal to separate the chiral drug sitafloxacin by HPLC method (determination of sitafloxacin isomers by HPLC method, Zhang Qiujia, Chen Lei, Zou Dechao, Zhang Meng, Chinese Journal of Antibiotics, Volume 37, March 2012 Phase 3), this method has defects such as expensive chromatographic column, long equilibration time of chromatographic column, short service life, low column efficiency, and only two isomer impurities of IMA and IMB in sitafloxacin isomers can be separated; Zhu Ziwei et al. used octadecylsilane bonded silica gel column as a chromatographic column, selected L-phenylalanine as a chiral additive, and copper sulfate as a coordination metal to separate sitafloxacin isomers by HPLC (HPLC method Research on the method for determining the isomers of sitafloxacin tablets, Zhu Ziwei, Mi Yinxiao, Zhang Xiaoli, Ye Hong, Chinese Journal of Antibiotics, Volume 40, Issue 12, December 2015), although the resolution of this method has been improved, but Only three isomer impurities of IMA, IMB and IMC in sitafloxacin can be separated

[0012] In addition to the chiral HPLC method, it has also been reported that chiral separation of sitafloxacin isomers by capillary electrophoresis was reported. For example, Zhuang Xiaoqing et al. used β-cyclodextrin and sulfated β-cyclodextrin as chiral additives. Separation of sitafloxacin STX and its three isomers IMA, IMB and IMC by electrophoresis (capillary electrophoresis chiral separation of sitafloxacin isomers, Xiaoqing Zhuang, Populus tomentosa, Bin Di, Shuanglu Xie, Journal of Pharmaceutical Analysis Chin J Pharm Anal 2012, 32 (8)), although the separation degree of this method has been improved, the separation degree is still low and the reproducibility is poor. Qualitative and quantitative analysis of IMD and IME isomers in Xingzhong

[0013] In summary, although there are currently many chiral analysis and detection methods for sitafloxacin isomers, there are problems such as high detection and analysis costs, complicated operations, low resolution, and poor flexibility. At most, only sitafloxacin can be separated The IMA, IMB and IMC impurities in the isomers cannot realize the qualitative and quantitative analysis of the IMD and IME isomer impurities in sitafloxacin, and cannot realize the accurate monitoring of the quality of sitafloxacin

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