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Method for detecting initial material II in apixaban through reversed-phase high performance liquid chromatography

A reversed-phase high-performance liquid chromatography and chromatographic detection technology is applied in the field of reversed-phase high-performance liquid chromatography to detect the starting material II of apixaban, which can solve the problems of cumbersome operation, fast peak output, long system equilibration time, etc. Accurate test results, enhanced control, and simple composition

Active Publication Date: 2015-11-11
CHENGDU BAIYU PHARMA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] Apixaban and its starting material II are weakly polar compounds, and the impurities in them are usually detected by reversed-phase high-performance liquid chromatography. For example, the quality standard of apixaban tablets uses octadecylsilane bonds The related substances in apixaban tablets are detected by reversed-phase high performance liquid chromatography with silica gel as filler. This method adopts gradient elution, the preparation of mobile phase is complicated, the system equilibration time is long, and the operation is cumbersome. The detection of Ⅱ, the peak is too fast, it is not suitable for the quality control of the starting material Ⅱ

Method used

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  • Method for detecting initial material II in apixaban through reversed-phase high performance liquid chromatography
  • Method for detecting initial material II in apixaban through reversed-phase high performance liquid chromatography
  • Method for detecting initial material II in apixaban through reversed-phase high performance liquid chromatography

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0039] 1. Determine the detection wavelength

[0040] Accurately weigh an appropriate amount of starting material II, and use mobile phase (acetonitrile-0.02mol / L potassium dihydrogen phosphate = 45:55) to prepare a solution with a concentration of 20 μg / ml as the test solution.

[0041] Take the above-mentioned test solution and scan it in the wavelength range of 200nm to 400nm. The test results are shown in Table 1.

[0042] The ultraviolet scanning result of the present invention of table 1

[0043] project

Peak wavelength(nm)

the peak

Valley wavelength(nm)

valley

Test solution

225.2

0.5711

241.8

0.0210

[0044] The test results show that the detection wavelength in the range of 220nm-230nm is suitable for the HPLC detection method of the present invention; preferably, the detection wavelength is 225±2nm.

[0045] 2. High performance liquid chromatography detection method

[0046] Detection by reversed-phase high-pe...

Embodiment 2

[0146] Embodiment 2 adopts reverse-phase high-performance liquid chromatography to detect:

[0147] Filler of the chromatographic column: the model of the chromatographic column is WatersSymmetryC18, the specifications are: the inner diameter is 4.6mm, the length is 150mm, and the particle size of the filler is 5μm;

[0148] Mobile phase: acetonitrile-0.02mol / L potassium dihydrogen phosphate (volume ratio 45:55);

[0149] Column temperature: 35°C;

[0150] Flow rate: 1.0ml / min;

[0151] Detection wavelength: 225nm;

[0152] Injection volume: 20 μl.

[0153] Prepare test solution according to the method of Example 1 and sample injection measurement, the result shows: starting material II (retention time is 23.253min) and the degree of separation of adjacent impurity is 52.578, theoretical plate number (calculated by starting material II ) is 144820, and the peak purity index of the starting material II is 1.000000. The reversed-phase high performance liquid chromatography o...

Embodiment 3

[0154] Embodiment 3 adopts reverse-phase high performance liquid chromatography to detect:

[0155] Filler of the chromatographic column: the model of the chromatographic column is WatersSymmetryC18, the specifications are: the inner diameter is 4.6mm, the length is 150mm, and the particle size of the filler is 5μm;

[0156] Mobile phase: acetonitrile-0.02mol / L potassium dihydrogen phosphate (volume ratio is 40:60);

[0157] Column temperature: 35°C;

[0158] Flow rate: 1.0ml / min;

[0159] Detection wavelength: 225nm;

[0160] Injection volume: 20 μl. .

[0161] Prepare test solution according to the method of Example 1 and sample injection measurement, the result shows: starting material II (retention time is 28.612min) and the degree of separation of adjacent impurities is 66.003, theoretical plate number (calculated by starting material II ) is 15827, and the peak purity index of the starting material II is 1.000000. The reversed-phase high performance liquid chromatog...

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Abstract

The invention discloses a method for detecting an initial material II in apixaban through reversed-phase high performance liquid chromatography. The method comprises the following steps: 1, preparing a sample solution; 2, detecting the sample through reversed-phase high performance liquid chromatography; and 3, calculating the content of every impurity and the content of total impurities in the sample through an area normalization technique. The method for detecting initial material II related substances in apixaban through reversed-phase high performance liquid chromatography realizes complete separation of the chromatographic peaks of the initial material II and all the impurities through a simple mobile phase component; and the detection result of the method is accurate and reliable, so the method makes control of the quality of the initial material in the apixaban synthesis process possible.

Description

technical field [0001] The invention relates to a method for detecting starting material II in apixaban by reverse-phase high-performance liquid chromatography. Background technique [0002] The chemical name of Apixaban is: 1-(4-methoxyphenyl)-7-oxo-6-[4-(2-oxo-piperidin-1-yl)phenyl]-4, 5,6,7-Tetrahydro-1H-pyrazol[3,4-C]-pyridine-3-carboxamide, molecular formula: C 25 h 25 N 5 o 4 , molecular weight: 459.50, the structural formula is as follows: [0003] [0004] Apixaban is not currently on the market in China, and the apixaban products that are currently on the market include Apixaban Tablets. Apixaban tablets are recorded in the "Registration Standards for Imported Drugs" of the State Food and Drug Administration, standard number: JX20120076. [0005] During the synthetic process of apixaban, two starting materials were used for directional synthesis, namely starting material I and starting material II. The chemical name of starting material I was: 1-[4-(2-oxopi...

Claims

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Application Information

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IPC IPC(8): G01N30/89
Inventor 孙毅宋务雄
Owner CHENGDU BAIYU PHARMA CO LTD
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