Method for detecting Afatinib and relevant substances thereof

A detection method and technology of related substances, which are applied in the detection of afatinib cis-isomers, afatinib and its related substances, can solve the problems of poor practicability and applicability, lack of universal adaptability, Heptafluorobutyric acid is expensive, etc., to achieve the effect of good peak shape, strong specificity and high sensitivity

Inactive Publication Date: 2016-03-23
HEBEI SHINEWAY PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0010] The instruments and equipment used in this method are expensive and do not have universal adaptability, and have strict requirements on the reagents and chromatographic columns used, among which heptafluorobutyric acid is expensive
In addition, when this method detects afatinib, there are few types of impurities that can be detected, and the resolution is poor.
It can be seen that the practicability and applicability of this method are poor

Method used

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  • Method for detecting Afatinib and relevant substances thereof
  • Method for detecting Afatinib and relevant substances thereof
  • Method for detecting Afatinib and relevant substances thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] (1) Detection conditions

[0038] Instrument: waters2695 high performance liquid chromatography, 2996PDA detector, detection wavelength: 260nm;

[0039] Chromatographic column: Phenomenex C18 (250mm×4.6mm, 5μm) chromatographic column;

[0040] Diluent: 30% acetonitrile;

[0041] Mobile phase: an aqueous solution of 0.2% formic acid+0.1% trifluoroacetic acid (take 2ml of formic acid and 1ml of trifluoroacetic acid solution and mix them in 1000ml of water) as mobile phase A, and acetonitrile as mobile phase B;

[0042] Flow rate: 1.0ml / min;

[0043] Column temperature: 40°C;

[0044] Injection volume: 10uL;

[0045] Carry out linear gradient elution according to Table 1.

[0046] Table 1

[0047]

[0048] (2) Detection steps

[0049] Preparation of resolution solution: Accurately weigh the cis-isomer (RC1), afatinib maleate, RC3 and RC4 and mix them in a certain proportion to form a resolution solution.

[0050] Preparation of reference solution: Take an ap...

Embodiment 2

[0055] According to the similar detection method of Example 1, wherein the detection wavelength is replaced by 255nm. The chromatogram of its reference substance is shown in Figure 5 , The chromatogram of the test product see Figure 6 .

Embodiment 3

[0057] According to the similar detection method of Example 1, wherein the detection wavelength is replaced by 265nm. The chromatogram of its reference substance is shown in Figure 7 , The chromatogram of the test product see Figure 8 .

[0058] Methodology Validation Test Results

[0059] According to the "Chinese Pharmacopoeia" 2015 edition guideline 9101 drug quality standard analysis method validation guideline part, the method validation test was carried out, and the chromatographic conditions for durability investigation included flow rate ± 0.1mL / min, column temperature ± 5 ℃, mobile phase Ratio ±2%, wavelength ±2nm. The results are shown in Table 2.

[0060] Table 2

[0061]

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Abstract

The invention relates to a method for detecting Afatinib, relevant substances thereof, and especially cis-isomers thereof. The method comprises the following steps: carrying out gradient elution by using a high performance liquid chromatograph, wherein Phenomenex C18 (250mm*4.6mm, 5[mu]m) is adopted as a chromatographic column, an aqueous solution containing 0.2% of formic acid and 0.1% of trifluoroacetic acid is adopted as a mobile phase A, acetonitrile is adopted as a mobile phase B, the detection wavelength is 255-265nm, and the column temperature is 35-45DEG C; and carrying out gradient elution under certain conditions. The method can effectively separate and detect Afatinib, relevant substances thereof, and especially cis-isomers thereof.

Description

technical field [0001] The invention relates to a detection method for afatinib and related substances thereof, in particular to a detection method for the cis-isomer of afatinib, which belongs to the technical field of pharmacy. Background technique [0002] Afatinib is an irreversible inhibitor of epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (Her-2) tyrosine kinases, and its dimaleate is indicated for the treatment of advanced Diseases such as non-small cell lung cancer (NSCLC). The chemical name of the compound is (2E)-4-[(3-chloro-4-fluorophenyl)amino]-6-{[4-(N,N-dimethylamino)-1-oxo-2 -buten-1-yl]amino}-7-((3S)-tetrahydrofuran-3-yloxy)-quinazoline, the structural formula is as follows: [0003] [0004] WO2007 / 085638A discloses a preparation method of afatinib, the synthesis route of which is as follows: [0005] [0006] The obtained afatinib crude product can be further refined and reacted with maleic acid to generate a...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N30/02
CPCG01N30/02G01N2030/027
Inventor 郑永亮张艳侠郝福康旺余大海
Owner HEBEI SHINEWAY PHARMA
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