Method used for measuring (E)3, 4, 5-triethoxy cinnamoyl chloride with LC-MS/MS

Abstract

The invention belongs to the technical field of medicine impurity analysis, and more specifically discloses a method used for measuring (E)3, 4, 5-triethoxy cinnamoyl chloride with LC-MS / MS. Accordingto the method, the method is invented based on the principle that (E)3, 4, 5-triethoxy cinnamoyl chloride is capable of reacting with diethylamine to generate stable compound (E) N, N-dimethyl-3, 4,5-triethoxy cinnamamide. A derivatization product is subjected to liquid chromatography tandem mass spectrometry analysis, and the conditions are as following: chromatographic column Agilent Poroshell120 EC-C18(100*2.1mm, 2.7<mu>m); mobile phase methanol-0.1% formic acid (V / V, 50:50); flow speed 0.4ml / min; column temperature 35 DEG C; sample introduction volume 5<mu>l; ion source electrospray iontrap (ESI); detection method positive ion multi-reaction monitoring mode; the monitoring ion pairs of (E) N, N-dimethyl-3, 4, 5-triethoxy cinnamamide are m / s 294.0 / 221.0 and 294.0 / 190.0. The method is high in specificity, low in detection limit, high in stability, high in recovery rate, and can be used for quality control of impurity (E)3, 4, 5-triethoxy cinnamoyl chloride in cinepazide maleate production process.

Description

technical field [0001] The invention belongs to the field of drug impurity analysis, and specifically discloses an analysis method for impurity (E) 3,4,5-trimethoxycinnamoyl chloride in cinepazide maleate. Background technique [0002] The chemical name of cinepazide maleate is (E)1-[(pyrrolidinecarbonyl)methyl]-4-(3,4,5-trimethoxycinnamoyl)piperazine maleate, commercial product Kelinao, a piperazine calcium antagonist [1] , has a variety of pharmacological effects, such as the synergistic effect of adenosine [2] , Vasodilator effect [3] , improve blood rheology [4] , widely used in the treatment of cardiovascular and cerebrovascular diseases [5～9] , first produced by the French Sanofi-Anentis company in 1970, and widely used in developed countries such as Europe and Japan, and launched in China in 2002 [1] . [0003] There are four main synthetic routes of cinepazide maleate, and (E)3,4,5-trimethoxycinnamoyl chloride is used as the raw material for the intermediate re...

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Problems solved by technology

[0029] In order to solve the deficiency that (E) 3,4,5-trimethoxycinnamoyl chloride impurity test method is difficult to reach the detection limit requirement in existing cinepazide, the present invention innovatively provides a kind of LC-MS / MS method to measure ( E) the method of 3,4,5-trimethoxycinnamoyl chloride, the test sample suspected of containing (E) 3,4,5-trimethoxycinnamoyl chloride is derivatized with diethylamine, and the derivatized test sample is obtained. Test samples, followed by LC-MS / MS for determination:

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