Detection method and application of 2-methoxyethylamine related substances

Abstract

The invention discloses a 2-methoxyethylamine related substance detection method and application, and the method comprises the following steps: S1, solution preparation, S2, interference peak elimination, S3, system adaptability verification, S4, impurity content detection, and S5, system performance re-confirmation: taking a proper amount of impurity reference substances, adding the impurity reference substances into a quantitative 2-methoxyethylamine reference substance volumetric flask at the same time, adding a proper amount of the 2-methoxyethylamine reference substance volumetric flask, and carrying out quantitative detection on the 2-methoxyethylamine reference substance volumetric flask; the components are uniformly mixed as a system applicability solution, a test solution: quantitative 2-methoxyethylamine is placed in a volumetric flask to serve as the test solution, and a reference solution: quantitative 2-methoxyethylamine is placed in the volumetric flask to serve as the reference solution. According to the detection method disclosed by the invention, the 2-methoxyethylamine and the four known impurities are relatively completely separated from each other, so that the attribution and the corresponding content of each impurity peak in the sample can be relatively accurately analyzed.

Description

Technical Field

[0001] The present invention relates to the field of detection, and in particular to a method for detecting related substances of 2-methoxyethylamine and its application. Background Art

[0002] 2-Methoxyethylamine, with the chemical formula C3H9NO, is a colorless and transparent liquid that exhibits significant basic characteristics under normal temperature and pressure. The amino unit in its molecular structure endows it with high chemical reactivity, enabling it to play a key role in a variety of chemical reactions. As an alkylamine compound, 2-methoxyethylamine not only has stable chemical properties but also is easy to undergo various derivatization reactions due to its unique structure, thus generating a variety of compounds with specific functions. As an important organic synthesis intermediate, 2-methoxyethylamine is widely used in the synthesis of fine chemicals such as pharmaceuticals, pesticides, and dyes. Its strong nucleophilicity makes it easy to undergo nucleophilic substitution reactions with various compounds, thereby introducing functional groups such as alkyl and acyl groups to construct complex molecular structures. During the process of drug research and development, 2-methoxyethylamine is often used to synthesize key structural units of target drug molecules. In the pharmaceutical field, the application of 2-methoxyethylamine is particularly extensive. It is not only an important raw material for the synthesis of various drugs but also directly used in the treatment of certain diseases due to its unique biological activity. For example, certain compounds containing the 2-methoxyethylamine structure are reported to have the function of potassium ion regulators and can be used to treat diseases related to potassium ion channels; there are also compounds as telomerase inhibitors that show good application prospects in the treatment of diseases such as cancer.

[0003] In the prior art, the detection method for 2-methoxyethylamine and related substances generally uses hydrogen flame gas chromatography. The system suitability test of this method only requires a purity ≥ 98.0% and does not study unknown impurities. Since there are many impurities generated during the production of 2-methoxyethylamine, in order to obtain 2-methoxyethylamine with high purity, the impurity points of this product have been studied. Currently, there are 4 common known impurities, and this method cannot accurately detect them. Summary of the Invention

[0004] To solve the deficiencies of the prior art, the present invention discloses a method for detecting related substances of 2-methoxyethylamine with a lower detection limit, higher resolution, simpler operation, and capable of simultaneously detecting all impurities.

[0005] The present invention discloses a method for detecting related substances of 2-methoxyethylamine and its application, which includes:

[0006] S1: Solution preparation, preparing a system suitability solution, a test solution, and a reference solution;

[0007] S2: Eliminate interference peaks. Program the temperature of the gas chromatograph without injecting the sample.

[0008] S3: Verify system suitability. Add the system suitability solution to the gas chromatograph and check the chromatogram to verify the system suitability.

[0009] S4: Detect the contents of various impurities. Add the system suitability solution, the test solution, and the reference solution to the gas chromatograph respectively, record the chromatograms respectively, and calculate the contents of various impurities according to the self-reference method of the main component.

[0010] S5: Re-confirm the system performance. Add the reference solution to the gas chromatograph and re-confirm the system suitability.

[0011] Wherein:

[0012] System suitability solution: Take appropriate amounts of each impurity reference substance and add them simultaneously to a volumetric flask containing a quantitative 2-methoxyethylamine reference substance, mix evenly to obtain the system suitability solution.

[0013] Test solution: Quantitative 2-methoxyethylamine in a volumetric flask is the test solution.

[0014] Reference solution: Quantitative 2-methoxyethylamine in a volumetric flask is the reference solution.

[0015] Further, the temperature rising rate of the chromatographic column in the gas chromatograph is 5 - 30 °C / min.

[0016] Further, the specific preparation method of the system suitability solution is: Take appropriate amounts of each impurity reference substance, add them to a volumetric flask containing a quantitative 2-methoxyethylamine reference substance, mix evenly to prepare a mixed stock solution containing 25 - 35 mg of various impurities per 1 ml. Then take 20 - 25 g of 2-methoxyethylamine, place it in a 20 - 30 ml volumetric flask, add 0.8 - 1.2 ml of the mixed stock solution, make up the volume to the mark with the reference solution, and shake well to obtain the system suitability solution.

[0017] Further, the specific requirements for verifying system suitability in S3 are to verify the resolution, tailing factor, and retention time of the system suitability solution.

[0018] When preparing the system suitability solution, take appropriate amounts of each impurity reference substance. Each impurity reference substance includes impurity I, impurity II, impurity III, and impurity IV.

[0019] In the chromatogram of the system suitability solution:

[0020] The retention time of the 2-methoxyethylamine peak is 6.5 - 10.0 minutes;

[0021] The resolution between 2-methoxyethylamine and the impurity II peak is greater than 1.5%.

[0022] The tailing factor of the 2-methoxyethylamine peak is within 0.9 - 1.2;

[0023] Among them, impurity I is methanol, impurity II is N-(2-methoxyethyl)methylamine, impurity III is 2-methoxy-N,N-dimethylethylamine, and impurity IV is 2-ethoxyethylamine.

[0024] Furthermore, for the test solution: Take 20 - 25 g of 2-methoxyethylamine, place it in a 20 - 30 ml volumetric flask, and make up to the mark with 2-methoxyethylamine, then shake well to obtain the test solution;

[0025] For the reference solution: Take 20 - 25 g of 2-methoxyethylamine, place it in a 20 - 30 ml volumetric flask, and make up to the mark with the reference substance of 2-methoxyethylamine, then shake well to obtain the reference solution.

[0026] Furthermore, the calculation formula for the self-reference method of the main component is content (%) = the peak area of the impurity in the test solution / the peak area of the main peak in the reference solution × 0.1%.

[0027] Furthermore, when detecting the contents of various impurities in S4, a gas chromatograph equipped with a flame ionization detector is used for detection;

[0028] The column length of the chromatographic column is set to 20 - 40 m, the inner diameter of the chromatographic column is set to 0.30 - 0.34 mm, and the liquid film thickness of the chromatographic column is set to 0.45 - 0.55 μm;

[0029] The carrier gas of the gas chromatograph is nitrogen.

[0030] Furthermore, the hydrogen pressure of the gas chromatograph is set to 0.05 - 0.10 MPa, the air pressure of the gas chromatograph is set to 0.05 - 0.10 MPa, the column inlet pressure of the gas chromatograph is set to 0.05 - 0.10 MPa, and the make-up gas pressure of the gas chromatograph is set to 0.05 - 0.10 MPa;

[0031] The sensitivity of the detector is set to 105 - 110, and the attenuation of the detector is set to 0.5 - 10;

[0032] The initial temperature of the column temperature of the chromatographic column is 10 - 100 °C, the retention time is 1 - 3 min, the vaporization temperature of the injection port is set to 100 - 250 °C, the detection temperature of the detector is set to 100 - 250 °C, then it is heated to 200 - 250 °C and held for 5 - 10 min, and the running time is 20 - 30 min;

[0033] The injection volume is 0.8 - 1.2 μl, and the split ratio is 47 - 53:1.

[0034] Furthermore, the application of the detection method for related substances of 2-methoxyethylamine in drug research and development, production, environmental monitoring, preparation of food contact materials, and academic research.

[0035] Beneficial effects:

[0036] The detection method and application of related substances of 2-methoxyethylamine in the present invention can completely separate 2-methoxyethylamine and four known impurities from each other. Therefore, it can accurately analyze the attribution and corresponding content of each impurity peak in the sample. In addition, this detection method also has the characteristics of high accuracy, good sensitivity, small blank interference, high stability, and low detection limit. Under the conditions of specific column temperature and heating rate, each substance peak in this detection method still has a large response and a good peak shape, and the known impurity peaks and unknown impurity peaks can be effectively separated, indicating that this method has strong adaptability and low requirements for working conditions. The gas chromatography analysis method established in the present invention for directly quantitatively determining the purity of 2-methoxyethylamine and related substances can obtain stable analysis results, which can guide the research and production of 2-methoxyethylamine; this method is simple, reliable, and has a low test price, suitable for enterprises to conduct routine analysis, and has practical value. Description of the drawings

[0037] Figure 1 It is the chromatogram of the systematic solution of the detection method for related substances of 2-methoxyethylamine in an embodiment of this application.

[0038] Figure 2 It is the chromatogram of the quantitation limit of the detection method for related substances of 2-methoxyethylamine in an embodiment of this application.

[0039] Figure 3 It is the chromatogram of the detection limit of the detection method for related substances of 2-methoxyethylamine in an embodiment of this application.

[0040] Figure 4 It is the chromatogram of the repeated experiments of an embodiment of the detection method for related substances of 2-methoxyethylamine in an embodiment of this application.

[0041] Figure 5 It is the chromatogram of the repeated experiments of an embodiment of another detection method for related substances of 2-methoxyethylamine in an embodiment of this application.

[0042] Figure 6 It is the chromatogram of the repeated experiments of an embodiment of another detection method for related substances of 2-methoxyethylamine in an embodiment of this application.

[0043] Figure 7 It is the chromatogram of the repeated experiments of an embodiment of another detection method for related substances of 2-methoxyethylamine in an embodiment of this application.

[0044] Figure 8It is the chromatogram of the comparative experiment of the detection method for related substances of 2-methoxyethylamine in the embodiments of the present application. Detailed implementation manners

[0045] In order to enable those skilled in the art to better understand the solution of the present invention, the technical solutions in the specific implementation manners of the present invention will be clearly and completely described below.

[0046] The present invention discloses a detection method and application for related substances of 2-methoxyethylamine, which includes:

[0047] S1: Solution preparation, preparing a system suitability solution, a test solution and a reference solution.

[0048] S2: Eliminating interference peaks, performing a programmed temperature rise on the gas chromatograph without injecting a sample. By performing a programmed temperature rise on the gas chromatograph without injecting a sample, any potential interference peaks from the solvent or instrument background can be effectively excluded. This step ensures that each peak in the subsequent chromatogram represents a real chemical component, rather than instrument noise or other non-specific signals.

[0049] S3: Verifying system suitability, adding the system suitability solution to the gas chromatograph, checking the chromatogram to verify the system suitability. Injecting the system suitability solution before the formal analysis of the sample can confirm whether the separation ability and stability of the chromatographic system meet the expected standards.

[0050] S4: Detecting the contents of various impurities, adding the system suitability solution, the test solution and the reference solution to the gas chromatograph respectively, recording the chromatograms respectively, and calculating the contents of various impurities according to the self-reference method of the main component. Using the self-reference method of the main component to calculate the impurity content, this method is based on the relative peak area comparison between the test solution and the reference solution, and can provide more accurate impurity quantification results.

[0051] S5: Reconfirming system performance, adding the reference solution to the gas chromatograph, and reconfirming the system suitability. After all sample analyses are completed, injecting the reference solution again to re-verify the system suitability. This double confirmation mechanism not only ensures the good state of the system at the beginning of the experiment, but also proves the stability and consistency of the system throughout the analysis process.

[0052] Among them, the system suitability solution: Take appropriate amounts of each impurity reference substance and add them simultaneously to a volumetric flask containing a quantified 2-methoxyethylamine reference substance, and mix evenly to obtain the system suitability solution; the test solution: Quantified 2-methoxyethylamine in a volumetric flask is the test solution; the reference solution: Quantified 2-methoxyethylamine in a volumetric flask is the reference solution. In order to improve the accuracy and reliability of the detection, the concentration of the test solution should be close to that of the reference solution to reduce the error caused by the difference in solution concentration. If the concentration of the test solution differs significantly from that of the reference solution, it may lead to deviation and unreliability of the detection results. This application combines system suitability verification, interference peak elimination, multiple confirmation mechanisms, and precise impurity content calculation to ensure efficient and accurate detection of 2-methoxyethylamine and its related substances.

[0053] As an implementation method, the heating rate of the chromatographic column in the gas chromatograph is 5 - 30 °C / min. Different compounds have different volatilities and retention characteristics at different temperatures. By adjusting the heating rate, the optimal separation conditions for the target compound and its impurities can be found, thereby improving the separation efficiency. A slower heating rate helps to better separate those compounds with close boiling points or difficult to separate, while a faster rate is suitable for rapid screening and preliminary identification. For some relatively simple samples or cases with more known components, using a higher heating rate such as 20 - 30 °C / min can significantly shorten the analysis time while ensuring the separation effect, improving work efficiency. A moderate heating rate such as 10 - 20 °C / min can ensure a smooth transition of the temperature gradient while maintaining a good separation effect, avoiding abnormal peak shapes or decreased sensitivity caused by too rapid temperature changes. The flexible heating rate design not only improves the separation efficiency, shortens the analysis time, enhances the resolution and sensitivity, but also greatly increases the adaptability of the method and the simplicity of operation. This makes the method have broad application prospects and practical value in fields such as drug research and development and quality control.

[0054] As an implementation method, the specific preparation method of the system suitability solution is as follows: Take appropriate amounts of each impurity reference substance and add them to a volumetric flask containing a quantitative 2-methoxyethylamine reference substance. Mix evenly to prepare a mixed stock solution containing 25 - 35 mg of various impurities per 1 ml. Then, take 20 - 25 g of 2-methoxyethylamine, place it in a 20 - 30 ml volumetric flask, add 0.8 - 1.2 ml of the mixed stock solution, and make up to the mark with the reference substance solution. Shake well to obtain the system suitability solution. By adding appropriate amounts of each impurity reference substance to a volumetric flask containing a quantitative 2-methoxyethylamine reference substance and mixing evenly, a mixed stock solution containing 25 - 35 mg of various impurities per 1 ml is ensured. This method guarantees the uniform distribution of impurities in the solution and reduces the possibility of too high or too low local concentrations. The preparation method of the system suitability solution ensures the efficiency and reliability of the experiment by precisely controlling the impurity concentration, providing a flexible operation range, simplifying the preparation process, and enhancing the detection accuracy. It not only improves the adaptability of the system and the simplicity of operation but also lays a solid foundation for subsequent sample analysis.

[0055] As an implementation method, the specific requirements for verifying the system suitability in S3 are to verify the resolution, tailing factor, and retention time of the system suitability solution. When preparing the system suitability solution, take appropriate amounts of each impurity reference substance, and each impurity reference substance includes impurity I, impurity II, impurity III, and impurity IV. In the chromatogram of the system suitability solution: the retention time of the 2-methoxyethylamine peak is 6.5 - 10.0 minutes, the resolution between the 2-methoxyethylamine peak and the impurity II peak is greater than 1.5%, and the tailing factor of the 2-methoxyethylamine peak is within 0.9 - 1.2. Among them, impurity I is methanol, impurity II is N-(2-methoxyethyl)methylamine, impurity III is 2-methoxy-N,N-dimethylethylamine, and impurity IV is 2-ethoxyethylamine.

[0056] When performing the system suitability test, if the resolution is less than 1.5%, change the column temperature and carrier gas flow rate until the column type is adjusted to achieve the best separation effect. The column temperature has a greater impact on the separation effect than the carrier gas flow rate. When the above parameters are abnormal, the following can be done:

[0057] Lower the column temperature: Appropriately lowering the column temperature can slow down the volatilization rate of the sample, reduce the intermolecular interaction, and avoid the appearance of tailing.

[0058] Replace the column: When the column has been used for too long, it must be replaced in a timely manner to ensure the accuracy of the analysis results.

[0059] Select a suitable column: Select a corresponding column according to the properties and molecular weight of the sample to ensure the separation effect of the sample in the column.

[0060] Adjust the flow rate: A reasonable flow rate can ensure that the sample is fully dissolved before entering the column, avoiding tailing caused by unnecessary interactions in the column.

[0061] As an implementation method, for the test solution: Take 20 - 25 g of 2 - methoxyethylamine, place it in a 20 - 30 ml volumetric flask, and make up to the mark with 2 - methoxyethylamine, shake well to obtain the test solution. For the reference solution: Take 20 - 25 g of 2 - methoxyethylamine, place it in a 20 - 30 ml volumetric flask, and make up to the mark with the reference substance of 2 - methoxyethylamine, shake well to obtain the reference solution.

[0062] As an implementation method, the calculation formula for the self - reference method of the main component is content (%) = the peak area of the impurity in the test solution / the peak area of the main peak in the reference solution × 0.1%.

[0063] As an implementation method, in the detection of the content of each impurity in S4, a gas chromatograph equipped with a flame ionization detector is used for detection. The column length of the chromatographic column is set to 20 - 40 m, the inner diameter of the chromatographic column is set to 0.30 - 0.34 mm, the liquid film thickness of the chromatographic column is set to 0.45 - 0.55 μm, and the carrier gas of the gas chromatograph is nitrogen.

[0064] As an implementation method, the hydrogen pressure of the gas chromatograph is set to 0.05 - 0.10 MPa, the air pressure of the gas chromatograph is set to 0.05 - 0.10 MPa, the column front pressure of the gas chromatograph is set to 0.05 - 0.10 MPa, the tail gas purge pressure of the gas chromatograph is set to 0.05 - 0.10 MPa, the sensitivity of the detector is set to 105 - 110, the attenuation of the detector is set to 0.5 - 10, the initial temperature of the column temperature of the chromatographic column is 10 - 100 °C, the retention time is 1 - 3 min, the vaporization temperature of the injection port is set to 100 - 250 °C, the detection temperature of the detector is set to 100 - 250 °C, heated to 200 - 250 °C, held for 5 - 10 min, the running time is 20 - 30 min, the injection volume is 0.8 - 1.2 μl, and the split ratio is 47 - 53:1.

[0065] As an implementation method, the detection method for the related substances of 2 - methoxyethylamine is applied in drug research and development and production, environmental monitoring, the preparation of food - contact materials, and academic research.

[0066] Examples:

[0067] Example 1

[0068] S1: Weigh appropriate amounts of each impurity reference substance and add them to a volumetric flask containing a quantitative amount of 2-methoxyethylamine reference substance to prepare a mixed impurity stock solution containing 30 mg per 1 ml. Weigh 23 g of 2-methoxyethylamine reference substance and place it in a 25-ml volumetric flask. Add 1 ml of the mixed impurity stock solution and dilute to the mark with the reference substance solution, then shake well to obtain the system suitability solution.

[0069] Weigh 23.5 g of the 2-methoxyethylamine sample and place it in a 25-ml volumetric flask. Dilute to the mark with 2-methoxyethylamine and shake well to obtain the test solution.

[0070] Weigh 23.5 g of 2-methoxyethylamine reference substance and place it in a 25-ml volumetric flask. Dilute to the mark with 2-methoxyethylamine reference substance and shake well to obtain the reference substance solution.

[0071] S2: Detect interfering peaks. Without injecting the sample, perform a programmed temperature rise on the gas chromatograph to detect interfering peaks.

[0072] S3: Verify system suitability. Add the system suitability solution to the gas chromatograph and check the chromatogram to verify the system suitability.

[0073] S4: Detect the content of each impurity. Add the system suitability solution, the test solution, and the reference substance solution to the gas chromatograph respectively, record the chromatograms respectively, and calculate the content of each impurity according to the self-reference method of the main component.

[0074] S5: Reconfirm the system performance. Add the reference substance solution to the gas chromatograph and reconfirm the consistency and stability of the system performance.

[0075] The types of each impurity are shown in Table 1 below:

[0076]

[0077] Table 1

[0078] System suitability test:

[0079] In the investigation of system suitability, the resolution between 2-methoxyethylamine and the adjacent impurity peak and each known impurity peak should be greater than 1.5%.

[0080] Test procedure:

[0081] Measure the system suitability solution, the test solution, and the reference substance solution respectively, inject them into the gas chromatograph, record the chromatograms, and calculate the content of each impurity according to the self-reference method of the main component:

[0082] Calculation formula: Content (%) = Peak area of the impurity in the test solution / Peak area of the main peak in the reference solution × 0.1%.

[0083] Among them, the chromatogram of the system suitability solution is asFigure 1 as shown

[0084] The differences between Examples 2 - 6 and Example 1 are shown in Table 2 below:

[0085] Table 2

[0086] Based on the spectra obtained from multiple tests, the performance of this detection method was calculated, and the detection results are shown in Table 3 below;

[0087] Table 3

[0088] The signal - to - noise ratio (S / N) of the quantitation limit of each substance is approximately 10 or greater than 10, the detection limit (S / N) is approximately 3 or greater than 3, and the quantitation limit should be at least less than one - fifth of the proposed limit; the relative standard deviation (RSD) of the peak areas of each substance in six consecutive injections of the quantitation limit solution should not exceed 15.0%.

[0089] From the data in the above table, it can be seen that the maximum quantitation limit among all substances is 90.36 pm, which is approximately 0.01% of the main component, indicating high sensitivity; the signal - to - noise ratios in the quantitation limit and detection limit of the solution in multiple tests all meet the requirements, and the RSD of each peak area in the quantitation limit solution is less than 15.0%, indicating that this method is sensitive.

[0090] Among them, the spectrum of the quantitation limit is as shown in Figure 2 and the spectrum of the detection limit is as shown in Figure 3 .

[0091] Referring to Figure 4 、 Figure 5 、 Figure 6 、 Figure 7 , the results of the test solution and the system suitability solution are calculated as shown in Table 4 below:

[0092] Table 4

[0093] Conclusion: It can be seen from the chromatogram that under the conditions of this method, the peak responses of each substance are large, the peak shapes are good, and the known impurity peaks and unknown impurity peaks can be effectively separated, indicating that this method has strong specificity.

[0094] Comparative Example:

[0095] Comparative Example 1

[0096] Chromatographic column: SE-54, capillary column length 30 m, inner diameter 0.32 mm. The analytical method used is programmed temperature detection. Specifically, the initial column temperature is 60 °C, the vaporization temperature is 250 °C, the detection temperature is 280 °C, the starting temperature is 60 °C, the holding time is 0.1 min, the heating rate is 10 °C / min, rising to 280 °C, the holding time is 11 min, the final temperature is 280 °C, the holding time is 10 min, the injection volume is 1 μl, the split ratio is 50:1, and the detector is FID.

[0097] The detected result spectrogram is as Figure 8 shown.

[0098] In Comparative Example 1, a suitable capillary column was not selected. It can be seen from the spectrogram that the peak shape has serious tailing, and the analysis effect of impurity points cannot be seen. The impurity points are included in the main peak, resulting in a relatively high product purity.

[0099] It should be understood that for those of ordinary skill in the art, improvements or transformations can be made according to the above description, and all such improvements and transformations shall fall within the protection scope of the appended claims of the present invention.

Claims

1. A method for detecting related substances of 2-methoxyethylamine and its application, characterized in that, Including: S1: Solution preparation, preparing system suitability solution, test solution and reference solution; S2: Eliminating interference peaks, performing programmed temperature rise on the gas chromatograph directly without injecting the sample; S3: Verifying system suitability, adding the system suitability solution to the gas chromatograph, and checking the chromatogram to verify the system suitability; S4: Detecting the contents of various impurities, adding the system suitability solution, test solution and reference solution to the gas chromatograph respectively, recording the chromatograms respectively, and calculating the contents of various impurities according to the self - reference method of the main component; S5: Re - confirming the system performance, adding the reference solution to the gas chromatograph, and re - confirming the system suitability; Wherein: System suitability solution: Take appropriate amounts of each impurity reference substance, and add them simultaneously to a volumetric flask containing a quantitative 2 - methoxyethylamine reference substance, and mix evenly to obtain the system suitability solution; Test solution: Quantitative 2 - methoxyethylamine in a volumetric flask is the test solution; Reference solution: Quantitative 2 - methoxyethylamine in a volumetric flask is the reference solution.

2. According to the detection method and application of related substances of 2 - methoxyethylamine described in claim 1, it is characterized in that: The heating rate of the chromatographic column in the gas chromatograph is 5 - 30 °C / min.

3. According to the detection method and application of related substances of 2 - methoxyethylamine described in claim 1, it is characterized in that: The specific preparation method of the system suitability solution is: Take appropriate amounts of each impurity reference substance, add them to a volumetric flask containing a quantitative 2 - methoxyethylamine reference substance, mix evenly to prepare a mixed stock solution containing 25 - 35 mg of various impurities per 1 ml. Then take 20 - 25 g of 2 - methoxyethylamine, place it in a 20 - 30 ml volumetric flask, add 0.8 - 1.2 ml of the mixed stock solution, and make up the volume to the scale with the reference solution, and shake well to obtain the system suitability solution.

4. According to the detection method and application of related substances of 2 - methoxyethylamine described in claim 3, it is characterized in that: The specific requirements for verifying system suitability in S3 are to verify the resolution, tailing factor and retention time of the system suitability solution; When preparing the system suitability solution, take appropriate amounts of each impurity reference substance, and each impurity reference substance includes impurity I, impurity II, impurity III and impurity IV; In the chromatogram of the system suitability solution: The retention time of the 2 - methoxyethylamine peak is 6.5 - 10.0 minutes; The resolution between the 2 - methoxyethylamine peak and the impurity II peak is greater than 1.5%; The tailing factor of the 2 - methoxyethylamine peak is within 0.9 - 1.2; Wherein, impurity I is methanol, impurity II is N - (2 - methoxyethyl) methylamine, impurity III is 2 - methoxy - N, N - dimethyl ethylamine, and impurity IV is 2 - ethoxyethylamine.

5. According to the detection method and application of related substances of 2 - methoxyethylamine described in claim 6, it is characterized in that: Test solution: Take 20 - 25 g of 2 - methoxyethylamine, place it in a 20 - 30 ml volumetric flask, and make up the volume to the scale with 2 - methoxyethylamine, and shake well to obtain the test solution; Reference solution: Take 20 - 25 g of 2 - methoxyethylamine and place it in a 20 - 30 ml volumetric flask. Dilute it to the mark with the reference substance of 2 - methoxyethylamine and shake well to obtain the reference solution.

6. The detection method and application of related substances of 2 - methoxyethylamine according to claim 1, characterized in that: The calculation formula of the main component self - control method is content (%) = the peak area of the impurity in the test solution / the peak area of the main peak in the reference solution × 0.1%.

7. The detection method and application of related substances of 2 - methoxyethylamine according to claim 1, characterized in that: In S4 for detecting the contents of various impurities, a gas chromatograph equipped with a flame ionization detector is used for detection; The column length of the chromatographic column is set to 20 - 40 m, the inner diameter of the chromatographic column is set to 0.30 - 0.34 mm, and the liquid film thickness of the chromatographic column is set to 0.45 - 0.55 μm; The carrier gas of the gas chromatograph is nitrogen.

8. The detection method and application of related substances of 2 - methoxyethylamine according to claim 7, characterized in that: The hydrogen pressure of the gas chromatograph is set to 0.05 - 0.10 MPa, the air pressure of the gas chromatograph is set to 0.05 - 0.10 MPa, the pre - column pressure of the gas chromatograph is set to 0.05 - 0.10 MPa, and the tail - blowing pressure of the gas chromatograph is set to 0.05 - 0.10 MPa; The sensitivity of the detector is set to 105 - 110, and the attenuation of the detector is set to 0.5 - 10; The initial temperature of the column temperature of the chromatographic column is 10 - 100 °C, the retention time is 1 - 3 min, the vaporization temperature of the injection port is set to 100 - 250 °C, the detection temperature of the detector is set to 100 - 250 °C, heated to 200 - 250 °C, and held for 5 - 10 min, and the running time is 20 - 30 min; The injection volume is 0.8 - 1.2 μl, and the split ratio is 47 - 53:

1.

9. The detection method and application of related substances of 2 - methoxyethylamine according to claim 1, characterized in that: The application of the detection method of related substances of 2 - methoxyethylamine in drug research and development, production, environmental monitoring, preparation of food - contact materials and academic research.

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