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Method for determining impurities in febuxostat and its preparation through high performance liquid chromatography

A technology of high-performance liquid chromatography and febuxostat, which is applied in the field of high-performance liquid chromatography to determine impurities in febuxostat and its preparations, can solve the problems of unsuitable analysis, unspecified, unsuitable detection process impurities and degradation Impurities and other issues

Active Publication Date: 2013-06-26
PHARMA RES INST OF BENCAO TIANYUAN OF BEIJING
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] In the prior art, there are many detection and analysis methods about febuxostat and impurities in its preparations, but they are not suitable for detecting the process impurities and degradation impurities that exist in the febuxostat prepared by the synthesis process that the inventor adopts (see table 1 list of impurities)
For example, patent 200910087796.8 provides a method for the determination of febuxostat related substances by high performance liquid chromatography, but it does not specify which impurities can be analyzed by this method, nor does it point out the specificity and sensitivity of the chromatographic method ; Patent 200910031295.8 provides a method for separating and analyzing febuxostat by high-performance liquid chromatography. Although the method points out which process impurities can be separated and analyzed, there are different process impurities due to different drug production processes. It is not applicable to the analysis of impurities and defects of febuxostat prepared by other synthetic processes; The method given in "method research" does not specify which impurities can be detected; the method given in "Determination of Related Substances of Febuxostat by HPLC" in "Strait Pharmacy" 2011, Volume 23, Issue 8, Page 76-78 It can only detect the four designated intermediate impurities. Whether it can detect other process impurities and degradation impurities needs further research; The method given in "Determination of Febuxostat Content and Related Substances" does not specify which impurities can be detected

Method used

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  • Method for determining impurities in febuxostat and its preparation through high performance liquid chromatography
  • Method for determining impurities in febuxostat and its preparation through high performance liquid chromatography
  • Method for determining impurities in febuxostat and its preparation through high performance liquid chromatography

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0092] Homemade febuxostat crude as raw material

[0093] Chromatographic conditions: chromatographic column with octadecylsilane bonded silica gel as filler; 0.01% triethylamine buffer solution as A mobile phase, methanol as B mobile phase, wherein the ratio range of A mobile phase to B mobile phase is 10: 90; detection wavelength 220nm; column temperature 30°C.

[0094] Preparation of impurity reference solution: take p-nitrobenzonitrile, 4-isobutoxy-1,3-benzenedicarbonitrile, 3-cyano-4-isobutoxythiobenzamide, 2- [3-cyano-4-isobutoxyphenyl]-4-methylthiazole-5-ethyl carboxylate, 4-isobutoxy-1,3-bis(4-methylthiazole-5-carboxylate Acid-2-yl)benzene, 2-[3 cyano-4-(2-methylpropoxy)phenyl]-4-methylthiazole, 2-[3-formamido-4-(2- Methylpropoxy)phenyl]-4-methylthiazole-5-carboxylic acid reference substance into a measuring bottle, add mobile phase to dilute to the mark, shake well as impurity reference solution.

[0095] Preparation of the test solution: Accurately weigh an approp...

Embodiment 2

[0100] Homemade febuxostat crude as raw material

[0101] Chromatographic conditions: octadecylsilane bonded silica gel as a chromatographic column; 0.05% triethylamine buffer solution is A mobile phase, methanol is B mobile phase, and the ratio range of A mobile phase to B mobile phase is 25: 75; detection wavelength 317nm; column temperature 30°C.

[0102] Preparation of impurity reference solution: take p-nitrobenzonitrile, 4-isobutoxy-1,3-benzenedicarbonitrile, 3-cyano-4-isobutoxythiobenzamide, 2- [3-cyano-4-isobutoxyphenyl]-4-methylthiazole-5-ethyl carboxylate, 4-isobutoxy-1,3-bis(4-methylthiazole-5-carboxylate Acid-2-yl)benzene, 2-[3 cyano-4-(2-methylpropoxy)phenyl]-4-methylthiazole, 2-[3-formamido-4-(2- Methylpropoxy)phenyl]-4-methylthiazole-5-carboxylic acid reference substance into a measuring bottle, add mobile phase to dilute to the mark, shake well as impurity reference solution.

[0103] Preparation of the test solution: Accurately weigh an appropriate amount o...

Embodiment 3

[0108] Homemade febuxostat crude as raw material

[0109] Chromatographic conditions: chromatographic column with octadecylsilane bonded silica gel as filler; 0.10% triethylamine buffer solution as A mobile phase, methanol as B mobile phase, wherein the ratio range of A mobile phase to B mobile phase is 40: 60; detection wavelength 310nm; column temperature 30°C.

[0110] Preparation of impurity reference solution: take p-nitrobenzonitrile, 4-isobutoxy-1,3-benzenedicarbonitrile, 3-cyano-4-isobutoxythiobenzamide, 2- [3-cyano-4-isobutoxyphenyl]-4-methylthiazole-5-ethyl carboxylate, 4-isobutoxy-1,3-bis(4-methylthiazole-5-carboxylate Acid-2-yl)benzene, 2-[3 cyano-4-(2-methylpropoxy)phenyl]-4-methylthiazole, 2-[3-formamido-4-(2- Methylpropoxy)phenyl]-4-methylthiazole-5-carboxylic acid reference substance into a measuring bottle, add mobile phase to dilute to the mark, shake well as impurity reference solution.

[0111] Preparation of the test solution: Accurately weigh an approp...

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Abstract

The invention relates to a medicine analysis method, and especially relates to a method for determining impurities in febuxostat and its preparation through high performance liquid chromatography. The method for detecting and analyzing impurities in febuxostat is established through treating an octadecylsilane bonded silica gel as a filler and a mixed solution comprising a triethylamine buffer solution and methanol as a mobile phase, and is sensitive, specific and comprehensive. The change of the impurities in the production and storage processes of febuxostat can be effectively detected through adopting the method, so the method is of great practical importance for the quality control of febuxostat and its preparation.

Description

technical field [0001] The invention relates to a drug analysis method, in particular to a method for measuring febuxostat and impurities in its preparations by high performance liquid chromatography. Background technique [0002] Febuxostat, chemical name: 2-[3-cyano-4-isobutoxyphenyl]-4-methylthiazole-5-carboxylic acid, is a new generation of non-purine xanthine oxidase inhibitors, can Significantly reduce blood uric acid concentration. In October 2004, the phase III clinical trial data released by the American College of Rheumatology showed that the curative effect of febuxostat is better than allopurinol, the current gold standard treatment drug for anti-gout. On May 5, 2008, IPSEN Company obtained the EU marketing authorization (trade name: ADENURIC, tablet, specifications: 80mg and 120mg), and on February 16, 2009, Takeda Pharmaceutical North America Company of Japan was approved by the U.S. FDA to go on the market in the United States ( Trade name: ULORIC, tablet, s...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N30/02
Inventor 顾群孙学伟李志刚肖万宏
Owner PHARMA RES INST OF BENCAO TIANYUAN OF BEIJING
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