Method for simultaneously determining contents of coexisting impurities in 2, 4-difluoroaniline

A technology for difluoroaniline and impurity content, which is applied in the field of analysis and detection in chemical medicine, can solve problems such as affecting the quality of medicines, patients' health, etc., and achieves the effects of easy control, accurate detection results, and simple operation.

Active Publication Date: 2019-12-31
HINYE PHARM CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] Limited by the current production technology and control technology level, there are often various impurities in the 2,4-difluoroaniline obtained in actual production, such as 1,3-dichlorobenzene, 2,6-difluoroaniline, 2,6 -Difluoronitrobenzene, 2,4-difluoronitrobenzene, 2,6-dichloronitrobenzene, 2,4-dichloronitrobenzene, etc., these impurities participate with 2,4-difluoroaniline In the subsequent drug synthesis, it will seriously affect the quality of the drug and the health of the patient
[0005] However, there is no relevant report on the quality control method of 2, 4-difluoroaniline at present. In order to comprehensively control the impurities in 2, 4-difluoroaniline and ensure that 2, 4-difluoroaniline is synthesized as a starting material In order to ensure the quality of flubenzylic acid and toloxacin, and to further ensure the drug safety of patients, it is necessary to invent a new and reasonable detection method, which can effectively control the content of impurities in 2, 4-difluoroaniline

Method used

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  • Method for simultaneously determining contents of coexisting impurities in 2, 4-difluoroaniline
  • Method for simultaneously determining contents of coexisting impurities in 2, 4-difluoroaniline
  • Method for simultaneously determining contents of coexisting impurities in 2, 4-difluoroaniline

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Experimental program
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Effect test

Embodiment 1

[0026] The raw materials used in the specific examples of the present invention are all known products, obtained by purchasing commercially available products, and the specific information is as follows in Table 1;

[0027] Table 1 Raw material information table

[0028]

[0029] A method for simultaneously detecting the content of coexisting impurities in 2,4-difluoroaniline provided by the present invention, the specific steps are as follows;

[0030] Chromatographic conditions

[0031] Instrument: Agilent 7890B Gas Chromatograph

[0032] Chromatographic column: 100% dimethylpolysiloxane (DB-1 30m×0.32mm×1.0μm or similar in polarity) as the stationary liquid

[0033] Detector: FID detector 250°C

[0034] Carrier gas: nitrogen

[0035] Carrier gas flow rate: 0.8ml / min

[0036] Diluent: Methanol

[0037] Injection port temperature: 200°C

[0038] Injection volume: 1.0μl

[0039] Heating program: the initial temperature is 50°C, maintained for 2 minutes, raised to 11...

Embodiment 2

[0053] System suitability test:

[0054] Add impurity need testing solution: preparation method is as embodiment 1.

[0055] Get and add impurity need testing solution, according to the chromatographic condition in the embodiment 1 continuous sample injection 6 needles, record chromatogram, detection result is shown in Table 4.

[0056] As can be seen from Table 4, in the 6 parts of continuous sampling adding impurity need testing solution, 2,6-difluoroaniline, 2,4-difluoroaniline, 1,3-dichlorobenzene, 2,6- The retention time RSDs of difluoronitrobenzene, 2,4-difluoronitrobenzene, 2,6-dichloronitrobenzene, and 2,4-dichloronitrobenzene peaks were all less than 0.1%, and the peak area RSDs were all less than 2.0%, indicating that the system suitability of each impurity under this method meets the requirements.

[0057] Table 4: System Suitability Test Results

[0058]

Embodiment 3

[0060] Detection limit:

[0061] Preparation of LOQ solution: Take 2,6-difluoroaniline, 2,4-difluoroaniline, 1,3-dichlorobenzene, 2,6-difluoronitrobenzene, 2,4-difluoronitrobenzene, 2,6-dichloronitrobenzene and 2,4-dichloronitrobenzene reference substances were diluted with methanol to make each 1ml contain about 0.4543μg of 2,6-difluoroaniline and 2,4-difluoroaniline About 0.5350 μg of aniline, about 0.9064 μg of 1,3-dichlorobenzene, about 0.7353 μg of 2,6-difluoronitrobenzene, about 0.7848 μg of 2,4-difluoronitrobenzene, about 0.7848 μg of 2,6-dichloronitrobenzene A mixed solution of about 0.5306 μg of benzene and about 0.8222 μg of 2,4-dichloronitrobenzene is obtained.

[0062] Get above-mentioned LOQ solution, measure by the chromatographic condition in the embodiment 1, detection result is as shown in table 5;

[0063] Table 5 Analysis of detection limit detection results

[0064]

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Abstract

The invention discloses a method for simultaneously determining contents of coexisting impurities in 2, 4-difluoroaniline. According to the method, the contents of coexisting impurities in 2, 4-difluoroaniline are detected by gas chromatography. With the method, the chromatographic peaks are high in separation degree and no mutual interference exists; the peak pattern is good and impurities such as 2, 6-difluoroaniline, 1, 3-dichlorobenzene, 2, 6-difluoronitrobenzene, 2, 4-difluoronitrobenzene, 2, 6-dichloronitrobenzene and 2, 4-dichloronitrobenzene can be accurately detected at the same time.The detection method is operated simply and is easy to control with the low detection cost; the method has a good linear relation, high specificity, precision, stability, sensitivity and repeatability, and high sample adding recovery rate and the detection result is accurate. The quality stability and clinical medication safety of new drugs such as diflunisal and tosufloxacin prepared by taking 2, 4-difluoroaniline as a starting material can be guaranteed.

Description

technical field [0001] The invention belongs to the field of analysis and detection in chemical medicine, and in particular relates to a method for simultaneously measuring the content of coexisting impurities in 2,4-difluoroaniline. [0002] technical background [0003] 2, 4-Difluoroaniline is a commonly used starting material in the organic synthesis of medicines. It is mainly used for the preparation of new drugs such as flufenesalic acid and toloxacin. Currently, there are three main synthetic methods reported in the literature. m-dichlorobenzene as raw material, prepared after nitration, fluorination, and reduction; or 1, 2, 4-trichlorobenzene as raw material, prepared after nitration, fluorination, and hydrogenolysis; and m-difluorobenzene as The raw material is obtained after low-temperature nitration and reduction with fuming nitric acid. [0004] Limited by the current production technology and control technology level, there are often various impurities in the 2,4...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): G01N30/02G01N30/06G01N30/30G01N30/32G01N30/60
CPCG01N30/02G01N30/06G01N30/30G01N30/32G01N30/6052G01N2030/324
Inventor 刘栋华廖漾匡前龙高玉贺程雪清
Owner HINYE PHARM CO LTD
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