Hydrochloric acid cefepime raw material and method for measuring content of N-methyl pyrrolidine in preparation thereof

Abstract

The invention relates to a measurement method of N-methylpyrrolidine content of cefepime dihydrochloride material and relative agent, for evaluating the quality of cefepime dihydrochloride material and relative agent. The invention discloses a liquid chromatograph which comprises using carboxylic cationic column as analysis column, uses a conductive detector to check, preparing flow phase, preparing sample solution and reference substance solution, using test method to respectively inject the sample solution and reference substance solution into a liquid chromatograph, recording high pressure liquid chromatographs, and calculating the N-methylpyrrolidine content of the sample. The inventive chromatograph system has easy balance, short sample test time, better repeatability in preserved time, stable baseline, durable column, high quality of chromatograph peak of N-methylpyrrolidine, better repeatability, accurate, simple and reliable process.

Description

technical field [0001] The invention relates to a quality detection and determination method for cefepime hydrochloride raw materials and preparations thereof. Background technique [0002] N-methylpyrrolidine is not only the raw material in the synthesis process of cefepime hydrochloride but also its degradation product. Currently, the 2005 edition of the Chinese Pharmacopoeia does not include cefepime and its preparations. There is no determination of N-methylpyrrolidine for other species. Foreign Pharmacopoeia has only USP.26 at present, and JPXIV is recorded, and the silica gel column that is all bonded sulfonic acid groups is the high-performance liquid chromatography of analytical column, when using this method to measure, the chromatographic system is difficult to balance and the measuring time is long (detection one The sample is about two hours), the retention time reproducibility is poor, the baseline drift is obvious, and the column life is short. In the 8th is...

AI Technical Summary

Problems solved by technology

Foreign Pharmacopoeia has only USP.26 at present, and JPXIV is recorded, and the silica gel column that is all bonded sulfonic acid groups is the high-performance liquid chromatography of analytical column, when using this method to measure, the chromatographic system is difficult to balance and the measuring time is long (detection one sample about two hours), retention time reproducibility is poor, baseline drift is obvious, column life is short

In the 8th issue of volume 13 of Chinese Journal of New Drugs in 2004, "the comparison of the determination method of N-methylpyrrolidine in cefepime hydrochloride" was reported in "influenced by the main drug cephalosporin hydrochloride, N-methylpyrrolidine in the test solution The peak shape is poor, the retention time drifts greatly, and the retention time difference with the N-methylpyrrolidine peak in the reference solution is often more than 10%", "time-consuming, a sample injection takes 2h", and there are domestic literature reports Determine its content with gas chromatography, but because N-methylpyrrolidine is both a synthetic raw material and a degradation product of cefepime, and cefepime hydrochloride is an acidic substance, and N-methylpyrrolidine is an alkaline substance, the two Part of the N-methylpyrrolidine is neutralized to form a salt when they coexist, and the salt-forming N-methylpyrrolidine cannot be directly gasified. complicated

If direct sample injection is adopted, the high temperature during gasification will degrade cefepime hydrochloride, and the salted N-methylpyrrolidine cannot be gasified, thereby affecting the measurement results; Encapsulate N-methylpyrrolidine, on the other hand cefepime hydrochloride is acidic, and the extraction of N-methylpyrrolidine that forms a salt under acidic conditions is not complete, so the organic solvent extraction method cannot accurately determine the concentration of cefepime hydrochloride. Content of N-Methylpyrrolidine

At present, gas chromatography cannot accurately measure the content of trace N-methylpyrrolidine impurities in cefepime hydrochloride

Images