Method for separating related substances from rivaroxaban

A separation method and technology for related substances, applied in the field of pharmaceutical analysis, can solve the problems of complicated gradient programming, and achieve the effects of good peak shape, good resolution and simple mobile phase composition.

Active Publication Date: 2020-02-28
HUNAN JIUDIAN PHARMA +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This method detects many related substances, but only detects one alkali-degraded impurity, and the gradient program design is complicated

Method used

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  • Method for separating related substances from rivaroxaban
  • Method for separating related substances from rivaroxaban
  • Method for separating related substances from rivaroxaban

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] Preparation of the test sample: Take 5 rivaroxaban tablets and place them in a 100ml measuring bottle, add an appropriate amount of diluent (mobile phase A:mobile phase B=40:60) about 70ml, ultrasonicate for 15min to dissolve, cool to room temperature, and dilute with Dilute the solution to the mark, shake well, filter, and take the continued filtration solution.

[0038] Mixed solution: Weigh about 25mg of rivaroxaban, put it in a 25ml measuring bottle, add an appropriate amount of diluent to dissolve, add acetooxamide, dioxalamide-urea, dechlorinated compound, 4,5-dichloro compound, oxygen Add appropriate amount of impurity solutions such as substituted phthalimide, diamide, triamide, intermediate 1, intermediate 3, impurity K and impurity M, and dilute to the mark with diluent to obtain the product.

[0039] Chromatographic conditions: mobile phase A is 0.01mol / L phosphoric acid solution, mobile phase B is acetonitrile, pH value of mobile phase A is 1.8, flow rate is...

Embodiment 2

[0046] Need testing solution and mixed solution preparation are consistent with embodiment 1.

[0047] Chromatographic conditions: mobile phase A is 0.01mol / L phosphoric acid solution, mobile phase B is acetonitrile, pH value of mobile phase A is 1.8, flow rate is 1.0ml / min, column temperature is 45°C, wavelength: 250nm;

[0048] time (min) A B 0 95% 5% 3 95% 5% 20 49% 51% 25 95% 5% 30 95% 5%

[0049] Get need testing solution, each 5ul of mixed solution inject high performance liquid chromatograph, and record chromatogram, obtain attached image 3 and 4 .

[0050] peak number keep time Peak height Peak area Tailing factor Resolution USP Theoretical plate number USP 1 10.122 0.272 1.552 1.068 / 71558.3 2 11.202 0.169 0.807 0.840 7.379 100504.5 3 11.323 0.393 1.899 1.134 0.887 123007.9 4 12.860 0.086 0.795 1.060 7.869 38713.0 5 13.184 0.343 2.603 0.847 1.506 98...

Embodiment 3

[0054] Need testing solution and mixed solution preparation are consistent with embodiment 1.

[0055] Chromatographic conditions: mobile phase A is 0.01mol / L phosphoric acid solution, mobile phase B is acetonitrile, pH value of mobile phase A is 2.0, flow rate is 1.0ml / min, column temperature is 45°C, wavelength: 250nm;

[0056] time (min) A B 0 92% 8% 12 65% 35% 20 49% 51% 24 92% 8% 30 92% 8%

[0057] Get need testing solution, each 5ul of mixed solution inject high performance liquid chromatograph, and record chromatogram, obtain attached Figure 5 and 6 .

[0058] peak number keep time Peak height Peak area Tailing factor Resolution USP Theoretical plate number USP 1 6.546 0.247 1.503 1.057 / 25413.0 2 7.705 0.154 0.853 0.982 7.403 43229.2 3 7.925 0.346 1.797 1.099 1.527 51313.6 4 9.657 0.076 0.710 1.296 8.937 24265.9 5 10.042 0.326 2.534 0.842 1.762 44299...

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Abstract

The invention relates to a method for separating related substances from rivaroxaban. The method uses high-performance liquid chromatography, the chromatographic column is a C18 column, and a mixed solution of a phosphoric acid solution and acetonitrile is used as a mobile phase for gradient elution. The method can separate and detect rivaroxaban and related substances in rivaroxaban tablets at the same time. The related substances comprise process impurities introduced in the synthesis of raw materials, and process degradation impurities generated in the preparation process of the preparation. Compared with the prior art, the impurity research is more comprehensive, and the separation method has the advantages of simple and convenient operation, good impurity separation, high sensitivity,and environmental friendliness.

Description

technical field [0001] The invention belongs to the field of medical analysis, in particular to a method for separating and detecting related substances in rivaroxaban by high performance liquid chromatography. Background technique [0002] Rivaroxaban (rivaroxban) is the world's first orally bioavailable factor Xa inhibitor, jointly developed by Johnson & Johnson and Bayer. The product name is Xarelto, which has been approved for marketing in more than 120 countries around the world. For the prevention and treatment of venous thrombosis. Compared with commonly used warfarin drugs, rivaroxaban has better absorption, stable blood drug concentration, less interference from drugs and food, quick onset and quick excretion, and does not need to go to the hospital regularly for blood coagulation tests, generally not The dosage is adjusted, and it is convenient for patients to use. The chemical name of rivaroxaban is: 5-chloro-nitrogen-({(5S)-2-oxo-3-[-4-(3-oxo-4-morpholinyl)phe...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N30/02G01N30/06G01N30/34
CPCG01N30/02G01N30/06G01N30/34
Inventor 邹金球张国丽何莉
Owner HUNAN JIUDIAN PHARMA
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