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A kind of detection method of quinazoline-7-ether compound and its related substances

A technology of ether compounds and related substances, applied in the field of chemical analysis, can solve problems such as high structural similarity, low chromatographic peak separation, difficult detection of quinazoline-7-ether compounds, and achieve high peak symmetry and high The effect of system adaptability and high precision

Active Publication Date: 2020-07-14
JIANGSU KANION PHARMA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, the most widely used method for quantitative detection of compounds is chromatography, but due to the high structural similarity of quinazoline-7-ether compounds and their related substances, quinazoline-7-ether compounds and their related The separation of chromatographic peaks in the process is low, which makes it difficult for existing chromatographic detection methods to be used for the detection of quinazoline-7-ether compounds and their related substances

Method used

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  • A kind of detection method of quinazoline-7-ether compound and its related substances
  • A kind of detection method of quinazoline-7-ether compound and its related substances
  • A kind of detection method of quinazoline-7-ether compound and its related substances

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0070] Determination of related substances in quinazoline-7-ether compound products

[0071] Instrument: Agilent High Performance Liquid Chromatograph

[0072] Column: Gemini C18 (4.6×150mm, 5μm)

[0073] Mobile phase A: 10mM ammonium acetate buffer solution (adjust the pH value to 5.0 with phosphoric acid)

[0074] Mobile phase B: methanol

[0075] Mobile Phase C: Acetonitrile

[0076] Detection wavelength: 253nm

[0077] Flow rate: 1.0ml / min

[0078] Injection volume: 20μl

[0079] Column temperature: 30℃

[0080] Dilution solvent: 10mM ammonium acetate buffer solution (adjust the pH to 5.0 with phosphoric acid), methanol and acetonitrile in a volume ratio of 55:30:15.

[0081] The elution procedure is shown in Table 1:

[0082] Table 1 Elution procedure

[0083] Time (min) Mobile phase A (%) Mobile phase B (%) Mobile phase C (%) 0553015 1544560 2035650 2510900

[0084] Test solution: Take 25 mg of the quinazoline-7-ether compound sample, put it in a 25ml measuring flask, add a diluent so...

Embodiment 2

[0093] System adaptability detection of detection method

[0094] 1. Prepare the solution

[0095] 1) Dilute solution: mix 10mM ammonium acetate buffer solution (adjust the pH value to 5.0 with phosphoric acid), methanol and acetonitrile according to the volume ratio of 55:30:15 and mix well;

[0096] 2) Blank solution: dilute solution;

[0097] 3). Impurity stock solution: take 5mg of impurity A (structure compound of formula (II)), impurity B (structure compound of formula (III)), and impurity C (structure compound of formula (IV)), accurately weigh and place them in the same Dissolve and dilute to the mark with a blank solution in a 20ml measuring flask, shake well;

[0098] 4) Resolution solution: Take about 25mg of quinazoline-7-ether compound, put it in a 25ml measuring flask, add 0.1ml of impurity stock solution, dissolve it with the diluted solution and dilute to the mark, shake it well.

[0099] 2. Chromatographic detection:

[0100] Inject the above blank solution and resolutio...

Embodiment 3

[0106] Specificity testing of testing methods

[0107] The strong degradation test is to accelerate the destruction of quinazoline-7-ether compounds under strong conditions, such as strong acid, strong alkali, strong oxidation, high temperature, and strong light. The purpose is to investigate the degradation products and The separation of main peaks and known impurities is compared with the amount of impurities produced and the reduction of main components to evaluate the effectiveness and applicability of the analytical method. At the same time, the DAD detector is used to check the peak purity: in the spectrum obtained from the degradation test, when the purity factor of the main component is greater than the threshold, it meets the requirements, that is, the main peak does not contain other unknown impurities.

[0108] According to the chromatographic conditions of Example 1, the samples treated with different strong degradation conditions were tested by high performance liquid ...

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Abstract

The invention relates to the field of chemical analysis, in particular to a detection method for a quinazoline-7-ether compound and related substances thereof. The detection method comprises the following step: detecting the content of a to-be-tested sample with the synthetic quinazoline-7-ether compound by using high performance liquid chromatography to respectively obtain the contents of the quinazoline-7-ether compound and the related substances thereof in the to-be-tested sample, wherein the quinazoline-7-ether compound has a structure shown in the formula I; the related substances of thequinazoline-7-ether compound comprise one or more of structural compounds shown in the formulas (II) to (IV); and a mobile phase used in the high performance liquid chromatography detection process isan ammonium acetate-phosphate buffer solution, methanol and acetonitrile. According to the detection method of the quinazoline-7-ether compound, disclosed by the invention, an ammonium acetate-phosphate buffer solution-methanol-acetonitrile elution system is adopted, so that the detection of the quinazoline-7-ether compound and other related substances is benefited. (The formula is shown in the description).

Description

Technical field [0001] The invention belongs to the field of chemical analysis, and particularly relates to a method for detecting quinazoline-7-ether compound and related substances. Background technique [0002] Quinazoline-7-ether compound, chemical name is (E)-4-(3-chloro-4-fluorophenyl)amino)-6-{[4-(N,N-dimethylamino)-1 -Oxo-2-buten-1-yl]amino}-7-((S)(3-oxabicyclo[3.1.0]hexane-6-methoxy)-quinazoline, its structure As shown in the following formula: [0003] [0004] The quinazoline-7-ether compound is a new compound modified by afatinib, and its preclinical pharmacodynamics shows strong activity. In July 2013, the US FDA approved quinazoline-7-ether compound pharmaceutical products for the treatment of advanced (metastatic) non-small cell lung cancer (NSCL) patients with epidermal growth factor receptor (EGFR) gene mutations. [0005] Quinazoline-7-ether compounds will inevitably produce intermediates and side-reaction products during the synthesis process. These intermediate...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): G01N30/02
CPCG01N30/02
Inventor 萧伟陈保来仲艳刘永友李家春郭庆明王振中
Owner JIANGSU KANION PHARMA CO LTD
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