Method for measuring content of succinic acid in trelagliptin succinate

Abstract

The invention relates to a method for measuring the content of succinic acid in trelagliptin succinate. According to the method, high performance liquid chromatography (HPLC) is adopted to measure thecontent of succinic acid in trelagliptin succinate. The method is simple and accurate, the sensitivity is high, and the repeatability is good. The method has been testified and can be applied to common analysis and quality control during the preparation process of trelagliptin succinate.

Description

technical field [0001] The invention belongs to the field of analytical chemistry, and in particular relates to a high-performance liquid chromatography method for determining the content of succinic acid in trexagliptin succinate. Background technique [0002] Trelagliptin Snccinate, the chemical name is 2-({6-[(3R)-3-aminopiperidin-1-yl]-3-methyl-2,4-dioxo-3, 4-dihydropyrimidine-1 (2 H )-yl}methyl)-4-fluorobenzonitrile succinate is an oral hypoglycemic drug developed by Takeda Corporation of Japan that can be taken once a week. In March 2015, it was approved for marketing in Japan for 2 type diabetes treatment. The structural formula of trexagliptin succinate is as follows: [0003] . [0004] In trexagliptin succinate, succinic acid and trexagliptin form a salt at a ratio of 1:1. Accurate determination of the content of succinic acid is of great significance to the quality control of trexagliptin succinate. There are many detection methods for related substances of...

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Problems solved by technology

[0004] In trexagliptin succinate, succinic acid and trexagliptin form a salt at a ratio of 1:1. Accurate determination of the content of succinic acid is of great significance to the quality control of trexagliptin succinate. Much is the related substance detection method of succinate trexagliptin, as CN104237421A, CN106546689A; There is not yet the content determination method report of succinic acid in succinate trexagliptin

At the same time, succinic acid is a commonly used medicinal raw material, and there are not many reports on its content determination method. What is often used at present is the determination method of succinic acid in the fourth part of the "Chinese Pharmacopoeia" 2015 edition. It is determined by NaOH (0.1mol / L ) titration solution to titrate the content of succinic acid, but when it is actually used to measure the content of succinic acid in Trexagliptin succinate, it is found that the measurement results are not accurate, which will affect the results of drug development or production; there are also patents CN103267755B, CN102323263A reported using Determination of succinic acid content by layer plate or scanning method, these methods have the disadvantage of inaccuracy

In addition, there are documents "Determination of succinic acid in shellfish ("Food Processing and Safety" Academic Symposium and 2010 Guangdong Provincial Food Society Annual Conference Proceedings, 294-298)", "Determination of succinic acid in pinellia (Chinese Journal of Hospital Pharmacy, 2015, 25(11): 1038-1039)", "Comparison of three assay methods for ferrous succinate tablets (Chinese Pharmacy, 2010, 21(21): 1994-1996)" and other reports , these documents use high performance liquid chromatography to determine the content of succinic acid in different categories, but they all use C18 columns. In the experiment, when C18 columns are used to detect succinate trexagliptin, there are poor peak shapes and incomplete peaks. Separation and other problems, so it is also not suitable for the determination of succinic acid content in trexagliptin succinate

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