A kind of detection method of impurities in parecoxib sodium synthesis process

Abstract

The invention belongs to the field of drug analysis and detection, in particular to a method for detecting impurities in a synthesis process of parecoxib sodium. The method for detecting impurities in the synthesis process of parecoxib sodium of the present invention comprises the following steps: dissolving a sample to be tested to obtain a solution to be tested; taking the solution to be tested and performing high-performance liquid chromatography analysis to obtain the content of impurities in the synthesis process; high-performance liquid chromatography The chromatographic column used in the analysis is an octadecylsilane-bonded silica gel chromatographic column, and gradient elution is adopted. The mobile phase A is disodium hydrogen phosphate solution with a pH of 2.5-3.5 and 0.01mol / L, and the mobile phase B is the volume ratio It is acetonitrile-methanol mixed solution of 75~85:15~25. The determination method can realize the accurate separation and detection of various impurities in parecoxib sodium raw materials or related products by applying the same analysis method, and has a wide coverage, especially, it can realize the detection of 4 kinds of excessively sulfonylated impurities; at the same time, the present invention The method has good separation effect, high sensitivity and accuracy, and can effectively evaluate and control the quality of parecoxib sodium.

Description

technical field [0001] The invention belongs to the field of drug analysis and detection, in particular to a method for detecting impurities in a synthesis process of parecoxib sodium. Background technique [0002] Parecoxib sodium, chemical name N-((4-(5-methyl-3-phenyl-4-isoxazolyl)phenyl)sulfonyl)propionamide sodium salt, is a Species-specific cyclooxygenase-2 (COX-2) inhibitor in the form of freeze-dried powder injection, is the first COX-2 inhibitor that can be administered intravenously and intramuscularly. The original research drug was approved for marketing in my country in 2008 and is mainly used for short-term treatment of postoperative pain. [0003] At present, in the field of drug synthesis, a common synthetic method of parecoxib sodium is as follows: [0004] [0005] The synthesis method comprises: using PRX-A as a starting material, through a sulfonylation reaction, an ammoniation reaction, an amidation reaction, a salt-forming reaction and necessary pu...

AI Technical Summary

Problems solved by technology

For example, the invention patent application with the application publication number CN108828127A discloses a liquid chromatography method for detecting related substances in parecoxib sodium and synthetic intermediates, which use pentafluorophenyl bonded silica gel and octadecylsilane bond respectively Silica gel is used as the chromatographic column filler, and the elution gradient is changed into two determinations of related substances Ⅰ and Ⅱ in parecoxib sodium intermediate valdecoxib and parecoxib. Using this method, although it can detect There are many kinds of process impurities, but the number of methods is large and the analysis cost is high, and the method has strong separation ability for the 5 positional isomers existing in the synthesis process, but it does not involve the unreacted Complete detection of starting materials, and comprehensive detection of over-sulfonylated derivative impurities that are very likely to exist in the reaction

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