Liquid chromatography method for detecting parecoxib sodium and related substances in synthesis intermediate

Abstract

The invention discloses a liquid chromatography method for detecting parecoxib sodium and related substances in a synthesis intermediate. A reverse phase efficient liquid chromatography method is adopted, pentafluorophenyl bonded silica gel and octadecyl silane bonded silica gel are taken as chromatographic column fillers, an ultraviolet detector is adopted, a mobile phase containing potassium dihydrogen phosphate is selected to carry out elution, the related substances, i.e., first related substances and second related substances, in parecoxib sodium intermediate valdecoxib and parecoxib aremeasured in two times; the mobile phases of the first related substances and the second related substances are both a mixed solution of methyl alcohol and a monopotassium phosphate aqueous solution. Two gradient methods of the liquid chromatography method are combined to finish simultaneously detecting 11 types of parecoxib sodium and the related substances of the intermediate of the parecoxib sodium, wherein fives types of position isomer impurities which are difficult to separate are contained. The liquid chromatography method has the advantages of high sensitivity, good repeatability and high accuracy.

Description

Technical field [0001] The invention belongs to the field of medical analysis, and specifically relates to a method for simultaneously detecting 12 related substances in parecoxib sodium and its synthetic intermediates by liquid chromatography, especially 5 positional isomers. Background technique [0002] The mechanism of action of non-steroidal anti-inflammatory drugs (NSAID) is to inhibit prostaglandin synthesis by inhibiting the activity of cyclooxygenase (COX), thereby exerting anti-inflammatory, antipyretic and analgesic effects. Conventional non-steroidal anti-inflammatory drugs inhibit constitutively expressed COX-1, while inhibiting inflammation-related or inducible COX-2. COX-1 will catalyze the production of prostaglandins required for normal cell function, so the application of conventional NSAIDs will inhibit COX-1 and cause certain side effects. In contrast, if the drug can selectively inhibit COX-2 but does not substantially inhibit COX-1, it will obtain anti-infl...

AI Technical Summary

Problems solved by technology

[0005] Although parecoxib sodium can now be produced on a large scale, the analysis and detection methods for related substances of parecoxib sodium have not yet been included in the pharmacopoeias of various countries, and the import registration standard of parecoxib sodium for injection mainly focuses on parecoxib sodium. The degradation impurities of coxib sodium cannot effectively separate some process impurities in raw materials and synthetic intermediates of raw materials, let alone accurately and quantitatively detect these impurities, so the quality of raw materials and preparations cannot be effectively guaranteed

After searching, the current related patents (such as CN201510181846.4) for the analysis method of related substances of parecoxib sodium can effectively separate and quantify some process impurities, but the control of positional isomers produced during the synthesis process is not sufficient

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