Method for detecting Apixaban intermediate II through reversed-phase high-performance liquid chromatogram

A reversed-phase high-performance liquid phase and chromatographic detection technology, which is applied in the field of reversed-phase high-performance liquid chromatography to detect intermediate II in the synthesis process of apixaban, can solve the problems of cumbersome operation, fast peak generation, and long system equilibrium time, and achieve The composition of the mobile phase is simple, the detection result is accurate, and the effect of strengthening the control

Active Publication Date: 2015-09-30
CHENGDU BAIYU PHARMA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0013] Apixaban and its intermediate 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 bonding Reversed-phase high-performance liquid chromatography with silica gel as a ...

Method used

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  • Method for detecting Apixaban intermediate II through reversed-phase high-performance liquid chromatogram
  • Method for detecting Apixaban intermediate II through reversed-phase high-performance liquid chromatogram
  • Method for detecting Apixaban intermediate II through reversed-phase high-performance liquid chromatogram

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0045] 1. Determine the detection wavelength

[0046] Accurately weigh an appropriate amount of Apixaban Intermediate II, and use the mobile phase (methanol-0.03mol / L disodium hydrogen phosphate=35:65) to prepare a solution with a concentration of 20μg / ml as the test solution.

[0047] Take the above-mentioned test solution and scan in the wavelength range of 200nm~400nm. The test results are shown in Table 1.

[0048] Table 1 UV scanning results of the present invention

[0049] Sample name

Peak wavelength nm / absorbance A

Valley wavelength nm / absorbance A

Intermediate II

279.0nm / 0.655

252nm / 0.517

[0050] The test results show that the detection wavelength is within the range of 270nm-290nm, which is suitable for the high performance liquid chromatography detection method of the present invention; preferably, the detection wavelength is 280±2nm.

[0051] 2. High performance liquid chromatography detection method

[0052] Use reversed-phase high performance liquid chromatograp...

Embodiment 2

[0151] Example 2 uses reversed-phase high performance liquid chromatography for detection:

[0152] Filler of the chromatographic column: The model of the chromatographic column is Welch Ultimate XB-C18, the specifications are: the inner diameter is 4.6mm, the length is 250mm, and the particle size of the filler is 5μm;

[0153] Mobile phase: methanol-0.03mol / L disodium hydrogen phosphate (volume ratio 30:70);

[0154] Column temperature: 35℃;

[0155] Flow rate: 1.0ml / min;

[0156] Detection wavelength: 280nm;

[0157] Injection volume: 20μl.

[0158] The test solution was prepared and sampled according to the method of Example 1. The results showed that the retention time of Apixaban Intermediate II was 25.113 min, the separation degree from adjacent impurities was 4.011, and the theoretical plate number (according to Intermediate II Calculated) is 38871, and the peak purity index of Apixaban Intermediate II is 1.000000. The reversed-phase high performance liquid chromatography of the ...

Embodiment 3

[0159] Example 3 uses reversed-phase high performance liquid chromatography for detection:

[0160] Filler of the chromatographic column: The model of the chromatographic column is Welch Ultimate XB-C18, the specifications are: the inner diameter is 4.6mm, the length is 250mm, and the particle size of the filler is 5μm;

[0161] Mobile phase: methanol-0.03mol / L disodium hydrogen phosphate (volume ratio 40:60);

[0162] Column temperature: 35℃;

[0163] Flow rate: 1.0ml / min;

[0164] Detection wavelength: 280nm;

[0165] Injection volume: 20μl.

[0166] The test solution was prepared and measured according to the method of Example 1. The results showed that the retention time of Apixaban Intermediate II was 15.013 min, the separation degree from adjacent impurities was 1.723, and the theoretical plate number (calculated according to Intermediate II) It is 64122 and the peak purity index of Apixaban Intermediate II is 1.000000. The reversed-phase high performance liquid chromatography of t...

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Abstract

The invention belongs to the field of analysis detection, and relates to a method for detecting an Apixaban intermediate II through a reversed-phase high-performance liquid chromatogram. The method includes the following steps of firstly, preparing a test solution; secondly, detecting the test solution through the reversed-phase high-performance liquid chromatogram; thirdly, calculating the content of each single impurity and all the impurities in the test solution according to an area normalization method. By means of the method, through simple mobile-phase components, the intermediate II can be completely separated from chromatographic peaks of all the impurities; meanwhile, the method is accurate and reliable in detection result and provides possibility for controlling the quality of the intermediate product in the Apixaban synthesis process.

Description

Technical field [0001] The invention relates to a method for detecting intermediate II in the synthesis process of 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-pyrazole[3,4-C]-pyridine-3-carboxamide, molecular formula: C 25 H 25 N 5 O 4 , Molecular weight: 459.50, the structural formula of apixaban is as follows: [0003] [0004] Apixaban is not currently on the market in China; apixaban products currently on the market include apixaban tablets, which are included in the "Registration Standards for Imported Drugs" of the State Food and Drug Administration. Standard number: JX20120076. [0005] In the synthesis process of apixaban, the starting material I and the starting material II are used for directional synthesis, the intermediate I is prepared through the reaction, and then the intermediate II is further obtai...

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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