Method for detecting related substances of 4-trifluoromethoxyaniline

Abstract

The invention relates to the technical field of pharmaceutical analysis, and particularly discloses a method for detecting related substances of 4-trifluoromethoxyaniline. According to the method disclosed by the invention, a capillary column which takes 2, 3-di-O-acetyl-6-0-TBDMS-gamma-cyclodextrin as a stationary liquid is used for carrying out gas chromatographic analysis on a 4-trifluoromethoxyaniline sample; according to the method, the four related substances in the 4-trifluoromethoxyaniline, namely trifluoromethoxybenzene, p-nitro trifluoromethoxybenzene, 2-trifluoromethoxyaniline and 3-trifluoromethoxyaniline, and the contents of the four related substances are accurately detected at the same time. The detection method is high in specificity, low in detection limit and quantification limit, good in linear relation, high in recovery rate, good in repeatability, high in stability, good in durability, easy and rapid to operate, low in detection cost and accurate and reliable in detection result, and guarantees can be provided for monitoring the quality stability and clinical medication safety of riluzole.

Description

Technical Field

[0001] The present invention relates to the technical field of pharmaceutical analysis, and particularly relates to a method for detecting related substances of 4-trifluoromethoxyaniline. Background Art

[0002] 4-Trifluoromethoxyaniline is a colorless transparent liquid and can be used as an intermediate in organic synthesis, and is often used as a fluorination reagent in organic synthesis reactions. In the synthesis process of 4-trifluoromethoxyaniline, related substances such as trifluoromethoxybenzene, p-nitrotrifluoromethoxybenzene, 2-trifluoromethoxyaniline, and 3-trifluoromethoxyaniline will inevitably be generated. Among them, trifluoromethoxybenzene and p-nitrotrifluoromethoxybenzene are material residues in the synthesis process, and 2-trifluoromethoxyaniline and 3-trifluoromethoxyaniline are isomeric impurities generated in the synthesis process.

[0003] The specific process route diagram of the synthesis of 4-trifluoromethoxyaniline is as follows:

[0004]

[0005] When 4-trifluoromethoxyaniline is used as the starting material of riluzole, its quality directly affects the purity of its finished product. Therefore, the content of related substances of 4-trifluoromethoxyaniline needs to be strictly controlled. At present, there is no detection method for related substances of 4-trifluoromethoxyaniline (trifluoromethoxybenzene, p-nitrotrifluoromethoxybenzene, 2-trifluoromethoxyaniline, 3-trifluoromethoxyaniline). It is very necessary to develop a detection method for related substances of 4-trifluoromethoxyaniline. Summary of the Invention

[0006] Aiming at the problem that related substances of 4-trifluoromethoxyaniline cannot be effectively detected in the prior art, the present invention provides a method for detecting related substances of 4-trifluoromethoxyaniline.

[0007] To solve the above technical problems, the technical solution provided by the present invention is:

[0008] A method for detecting related substances of 4-trifluoromethoxyaniline, wherein the related substances of 4-trifluoromethoxyaniline include trifluoromethoxybenzene, p-nitrotrifluoromethoxybenzene, 2-trifluoromethoxyaniline, and 3-trifluoromethoxyaniline, and gas chromatography is used for detection, comprising the following steps:

[0009] Preparation of test solution: Dissolve the 4-trifluoromethoxyaniline sample in a solvent to obtain a test solution;

[0010] Preparation of reference solution: Dissolve the reference substances of trifluoromethoxybenzene, p-nitrotrifluoromethoxybenzene, 2-trifluoromethoxyaniline, and 3-trifluoromethoxyaniline in a solvent to obtain a reference solution;

[0011] The reference solution and the test solution are detected by gas chromatography. The chromatographic conditions of the gas chromatography include:

[0012] Chromatographic column: a capillary column using 2,3-di-O-acetyl-6-O-TBDMS-γ-cyclodextrin as the stationary liquid;

[0013] The temperature programming is as follows: the initial temperature is 38 °C to 42 °C, maintained for 2 min to 4 min, and then heated at a rate of 8 °C / min to 12 °C / min to 195 °C to 205 °C, and maintained for 8 to 12 min;

[0014] The inlet temperature is 195 °C to 205 °C;

[0015] The detector temperature is 245 °C to 255 °C.

[0016] The detection method for impurities in 4-trifluoromethoxyaniline provided by the present invention uses a capillary column with 2,3-di-O-acetyl-6-O-TBDMS-γ-cyclodextrin as the stationary liquid as the chromatographic column to perform gas chromatography analysis on the 4-trifluoromethoxyaniline sample, realizing the accurate detection of four related substances, namely trifluoromethoxybenzene, p-nitrotrifluoromethoxybenzene, 2-trifluoromethoxyaniline, and 3-trifluoromethoxyaniline, and their contents in 4-trifluoromethoxyaniline. By limiting the temperature programming of the gas chromatography and the temperatures of the inlet and detector, etc., the present invention improves the peak response intensity of the test solution and the reference solution, thereby improving the detection accuracy. This detection method has strong specificity, low detection limit and quantification limit, good linear relationship, high recovery rate, good repeatability, strong stability, good durability, and is simple and fast to operate, with low detection cost and accurate and reliable detection results. It can provide data support for the effective control of the quality of 4-trifluoromethoxyaniline during the production process. As the starting material of riluzole, 4-trifluoromethoxyaniline provides guarantee for the quality stability and clinical medication safety of riluzole.

[0017] Preferably, the solvent is dichloromethane.

[0018] Preferably, the specification of the chromatographic column is 30 m × 0.25 mm, and the filler diameter is 0.25 μm.

[0019] More preferably, the chromatographic column is a Merk Gamma DEX-225 chromatographic column.

[0020] Preferably, the concentration of 4-trifluoromethoxyaniline in the test solution is 8 mg / mL to 12 mg / mL.

[0021] Preferably, the concentration of trifluoromethoxybenzene in the reference solution is 28 μg / mL to 30 μg / mL.

[0022] Preferably, the concentration of p-nitrotrifluoromethoxybenzene in the reference solution is 28 μg / mL to 30 μg / mL.

[0023] Preferably, the concentration of 2-trifluoromethoxyaniline in the reference solution is 28 μg / mL to 30 μg / mL.

[0024] Preferably, the concentration of 3-trifluoromethoxyaniline in the reference solution is 28 μg / mL to 30 μg / mL.

[0025] Preferably, the chromatographic conditions of the gas chromatography further include: the detector is a flame ionization detector.

[0026] Preferably, the chromatographic conditions of the gas chromatography further include: the carrier gas is nitrogen.

[0027] Preferably, the chromatographic conditions of the gas chromatography further include: the column flow rate is 1.8 mL / min to 2.2 mL / min.

[0028] Preferably, the chromatographic conditions of the gas chromatography further include: the injection volume is 0.8 μL to 1.2 μL.

[0029] Preferably, the chromatographic conditions of the gas chromatography further include: the split ratio is (5 - 15):1.

[0030] The detection method of the present invention using gas chromatography can accurately detect the related substances of 4-trifluoromethoxyaniline, and is applicable to the detection of trifluoromethoxybenzene, p-nitrotrifluoromethoxybenzene, 2-trifluoromethoxyaniline and 3-trifluoromethoxyaniline in 4-trifluoromethoxyaniline, solving the problem that trifluoromethoxybenzene, p-nitrotrifluoromethoxybenzene, 2-trifluoromethoxyaniline and 3-trifluoromethoxyaniline in 4-trifluoromethoxyaniline cannot be effectively controlled at present. And this detection method is simple to operate and has high precision, having the value of popularization and practical application. Description of the Drawings

[0031] Figure 1 Is the gas chromatogram of the blank solvent in Example 1, wherein, peak 1 is dichloromethane;

[0032] Figure 2 Is the gas chromatogram of the reference solution in Example 1, wherein, peak 1 is dichloromethane, peak 2 is trifluoromethoxybenzene, peak 3 is 2-trifluoromethoxyaniline, peak 4 is 3-trifluoromethoxyaniline, and peak 5 is p-nitrotrifluoromethoxybenzene;

[0033] Figure 3It is the gas chromatogram of the test sample solution in Example 1. Among them, peak 1 is dichloromethane, peak 3 is 2-trifluoromethoxyaniline, peak 4 is 3-trifluoromethoxyaniline, and peak 6 is 4-trifluoromethoxyaniline;

[0034] Figure 4 It is the gas chromatogram of the spiked test sample solution in Example 1. Among them, peak 1 is dichloromethane, peak 2 is trifluoromethoxybenzene, peak 3 is 2-trifluoromethoxyaniline, peak 4 is 3-trifluoromethoxyaniline, peak 5 is p-nitrotrifluoromethoxybenzene, and peak 6 is 4-trifluoromethoxyaniline;

[0035] Figure 5 It is the gas chromatogram of the standard solution in Comparative Example 1. Among them, 2 is trifluoromethoxybenzene, 3 is 2-trifluoromethoxyaniline, 4 is 3-trifluoromethoxyaniline, 5 is p-nitrotrifluoromethoxybenzene, and 6 is 4-trifluoromethoxyaniline;

[0036] Figure 6 It is the gas chromatogram of the standard solution of 3-trifluoromethoxyaniline and 4-trifluoromethoxyaniline in Comparative Example 2. Among them, 4 is 3-trifluoromethoxyaniline and 6 is 4-trifluoromethoxyaniline. Detailed implementation manners

[0037] The technical solutions of the present invention will be clearly and completely described below. It should be understood that the specific embodiments described herein can enable those skilled in the art to understand the present invention more comprehensively, but do not limit the present invention within the scope of the described embodiments.

[0038] Example 1

[0039] This example provides a detection method for related substances of 4-trifluoromethoxyaniline, which specifically includes the following steps:

[0040] (1) Solution preparation

[0041] Blank solvent: Dichloromethane;

[0042] Test sample solution: Accurately weigh 100 mg of 4-trifluoromethoxyaniline sample, add dichloromethane to a 10 mL volumetric flask for volume fixation to prepare a 10 mg / mL test sample solution of 4-trifluoromethoxyaniline;

[0043] Reference stock solution: Take appropriate amounts of trifluoromethoxybenzene, p-nitrotrifluoromethoxybenzene, 2-trifluoromethoxyaniline, and 3-trifluoromethoxyaniline, accurately weigh them, and prepare a mixed solution containing approximately 300 μg of each in 1 mL with dichloromethane as the stock solution;

[0044] Reference solution: Take an appropriate amount of the stock solution and prepare a mixed solution containing about 30 μg of benzotrifluoride, p-nitrobenzotrifluoride, 2-(trifluoromethoxy)aniline, and 3-(trifluoromethoxy)aniline in each 1 mL with dichloromethane as the reference solution.

[0045] Spiked test solution: Take 100 mg of 4-(trifluoromethoxy)aniline sample, accurately weigh it, place it in a 10 mL volumetric flask, add 1 mL of the stock solution, dissolve it with dichloromethane and dilute to the mark, shake well to obtain the spiked test solution.

[0046] (2) The chromatographic conditions of the specific gas chromatography method include:

[0047] Use a Merk Gamma DEX-225 chromatographic column (30 m × 0.25 mm, 0.25 μm);

[0048] The temperature programming of the gas chromatography is as follows: the initial temperature is 40 °C, maintained for 3 min, then heated at a rate of 10 °C / min to 200 °C and maintained for 10 min;

[0049] The detector is a flame ionization detector (FID), the injection port temperature is 200 °C, and the detector temperature is 250 °C;

[0050] The carrier gas is nitrogen;

[0051] Column flow rate: 2 mL / min;

[0052] The injection volume is 1 μL;

[0053] The split ratio is 10:1.

[0054] Example 2

[0055] Use the above gas chromatography method to detect the above blank solvent, test solution, reference solution, and spiked test solution. Among them, the gas chromatogram results of the blank solvent, reference solution, test solution, and spiked test solution are as Figures 1-4 shown. Test the resolution of each impurity in the spiked test solution, and the test results are shown in Table 1. It can be seen from Figures 1-4 and Table 1 that for the method for detecting impurities in 4-(trifluoromethoxy)aniline provided in this example, the blank solvent does not interfere with the detection of each component, the resolution between each component meets the requirements, and the method has good specificity.

[0056] Table 1 Detection results of the resolution of each component

[0057] Component Retention time (min) Resolution Dichloromethane 2.127 -- Trifluoromethoxybenzene 4.698 24.888 2-Trifluoromethoxyaniline 11.273 87.284 3-Trifluoromethoxyaniline 13.306 36.181 4-Trifluoromethoxyaniline 13.631 2.559 p-Nitrophenyl trifluoromethyl ether 14.216 4.494 Unknown impurity 1 14.357 2.126 Unknown impurity 2 16.562 32.613

[0058] Example 3

[0059] Detection limit and quantification limit:

[0060] (1) Detection method:

[0061] Take appropriate amounts of trifluoromethoxybenzene, p-nitrotrifluoromethoxybenzene, 2-trifluoromethoxyaniline, 3-trifluoromethoxyaniline, and 4-trifluoromethoxyaniline, accurately weigh them, and prepare a solution containing approximately 300 μg of each in 1 mL of dichloromethane. Accurately measure appropriate amounts of the mixed solution respectively, perform serial dilution, and detect. When the peak height of the chromatogram is about 3 times the baseline noise, it is the detection limit; when the peak height of the chromatogram is about 10 times the baseline noise, it is the quantitation limit. The maximum RSD of the peak areas of each component measured 6 times is 5.78%, indicating that the method provided by this scheme has good repeatability of the quantitation limit.

[0062] The results of the detection limit and quantitation limit are shown in Tables 2 - 3:

[0063] Table 2 Results of the quantitation limit and detection limit tests

[0064]

[0065] Table 3 Results of the repeatability test of the quantitation limit

[0066]

[0067]

[0068] Example 4

[0069] Linearity investigation:

[0070] Accurately weigh appropriate amounts of the reference substances of trifluoromethoxybenzene, p-nitrotrifluoromethoxybenzene, 2-trifluoromethoxyaniline, and 3-trifluoromethoxyaniline, prepare a series of reference substance solutions according to the preparation method of Example 1, and perform detection according to the detection method and chromatographic conditions of Example 1 of the present invention. As can be seen from Tables 4 - 8, the linear relationships of each component are good, indicating that the method provided by this scheme has a good linear relationship.

[0071] The linearity results are shown in Tables 4 - 8:

[0072] Table 4 Results of the linearity test of trifluoromethoxybenzene

[0073]

[0074] Table 5 Results of the linearity test of 2-trifluoromethoxyaniline

[0075]

[0076] Table 6 Results of the linearity test of 3-trifluoromethoxyaniline

[0077]

[0078] Table 7 Linear test results of 4-trifluoromethoxyaniline

[0079]

[0080] Table 8 Linear test results of p-nitrotrifluoromethoxybenzene

[0081]

[0082]

[0083] Example 5

[0084] Investigation of recovery rate:

[0085] Prepare the reference substance stock solution according to the method of Example 1. Take 100 mg of 4-trifluoromethoxyaniline sample, accurately weigh it, place it in a 10 mL volumetric flask, accurately add appropriate volumes of the mixed stock solution respectively and dilute to the mark, shake well. Each concentration is in parallel for 3 portions as the test solutions with low, medium and high recovery rates. Carry out the detection according to the detection method and chromatographic conditions of Example 1 of the present invention. As can be seen from Tables 9 - 12, the recovery rates of trifluoromethoxybenzene, p-nitrotrifluoromethoxybenzene, 2-trifluoromethoxyaniline and 3-trifluoromethoxyaniline in the present invention are all between 80% and 120%, and the maximum RSD is 7.80%, indicating that the method provided by the present invention has good accuracy.

[0086] Table 9 Detection results of the recovery rate of trifluoromethoxybenzene

[0087]

[0088] Table 10 Detection results of the recovery rate of 2-trifluoromethoxyaniline

[0089]

[0090] Table 11 Detection results of the recovery rate of 3-trifluoromethoxyaniline

[0091]

[0092] Table 12 Detection results of the recovery rate of p-nitrotrifluoromethoxybenzene

[0093]

[0094] Example 6

[0095] Repeatability:

[0096] Accurately weigh the 4-trifluoromethoxyaniline sample, prepare the test solution according to the method provided in Example 1, and perform the detection under the gas chromatography conditions provided in Example 1. From the data in Table 13, it can be seen that the detection results of the related substances in the same batch of 4-trifluoromethoxyaniline detected by the detection method provided by the present invention are basically the same, with good repeatability.

[0097] The repeatability results are shown in Table 13:

[0098] Table 13 Repeatability Results

[0099]

[0100]

[0101] Example 7

[0102] Investigation on solution stability:

[0103] Accurately weigh 4-trifluoromethoxyaniline and related substances, prepare the test solution and the reference solution according to the preparation method provided in Example 1, and perform the detection under the chromatographic conditions provided in Example 1 after standing at room temperature for 0 h, 2 h, 4 h, 8 h, and 14 h respectively. From Tables 14 - 15, it can be seen that after standing at room temperature for 14 h, the RSD of the peak areas of each component is less than 10%; there is no obvious difference in the detection results of the test solution and the reference solution at each time point.

[0104] The stability results of the solution are shown in Tables 14 - 15:

[0105] Table 14 Stability Results of the Reference Solution

[0106]

[0107] Table 15 Stability Results of the Test Solution

[0108]

[0109] Example 8

[0110] Robustness:

[0111] Accurately weigh 4-trifluoromethoxyaniline and related substances, prepare the spiked test solution according to the preparation method provided in Example 1, change the initial temperature, heating rate, inlet temperature, and detector temperature respectively, keep other detection conditions unchanged, and perform the detection according to the detection method and chromatographic conditions of Example 1 of the present invention. From Tables 16 - 19, it can be seen that when each condition is changed, the resolution of each component meets the requirements, indicating that the method provided by this scheme has good robustness.

[0112] The final resolution results of each substance are shown in Tables 16 - 19:

[0113] Table 16 Resolution at Different Initial Temperatures

[0114] Standard conditions Initial temperature 38°C Initial temperature 42°C Dichloromethane -- -- -- Trifluoromethoxybenzene 24.48 29.708 21.575 2-Trifluoromethoxyaniline 86.903 88.909 85.642 Unknown impurity 1 12.817 13.078 13.42 3-Trifluoromethoxyaniline 17.289 17.615 18.19 4-Trifluoromethoxyaniline 2.278 2.285 2.163 p-Nitrophenyl trifluoromethyl ether 4.305 4.392 4.182 Unknown impurity 2 2.151 2.168 2.127 Unknown impurity 3 33.079 33.429 33.103 Unknown impurity 4 16.428 16.617 16.233

[0115] Table 17 Resolution at Different Heating Rates

[0116] Standard conditions Heating rate 9°C / min Heating rate 11°C / min Dichloromethane -- -- -- Trifluoromethoxybenzene 24.48 24.577 24.639 2-Trifluoromethoxyaniline 86.903 90.237 84.137 Unknown impurity 1 12.817 13.405 13.225 3-Trifluoromethoxyaniline 17.289 18.855 17.329 4-Trifluoromethoxyaniline 2.278 2.284 2.122 p-Nitrophenyl trifluoromethyl ether 4.305 4.339 4.236 Unknown impurity 2 2.151 1.668 2.549 Unknown impurity 3 33.079 33.777 32.097 Unknown impurity 4 16.428 17.705 15.705

[0117] Table 18 Resolution at Different Injector Temperatures

[0118]

[0119]

[0120] Table 19 Resolution at Different Detector Temperatures

[0121] Standard conditions Detector 245°C Detector 255°C Dichloromethane -- -- -- Trifluoromethoxybenzene 24.48 25.088 24.334 2-Trifluoromethoxyaniline 86.903 87.693 86.683 Unknown impurity 1 12.817 13.143 12.937 3-Trifluoromethoxyaniline 17.289 17.833 17.533 4-Trifluoromethoxyaniline 2.278 2.276 2.281 p-Nitrophenyl trifluoromethyl ether 4.305 4.337 4.362 Unknown impurity 2 2.151 2.151 2.144 Unknown impurity 3 33.079 33.187 32.632 Unknown impurity 4 16.428 16.41 16.599

[0122] Comparative Example 1

[0123] This comparative example provides a method for detecting related substances of 4-trifluoromethoxyaniline. Different from Example 1: The Merk Gamma DEX-225 chromatographic column was replaced with a capillary column with 100% dimethyl polysiloxane as the stationary liquid (DB-1701 chromatographic column, 30m * 0.32mm * 0.25μm), and other conditions were the same as those in Example 1;

[0124] Trifluoromethoxybenzene, 2-trifluoromethoxyaniline, 3-trifluoromethoxyaniline, 4-trifluoromethoxyaniline, and p-nitrotrifluoromethoxybenzene standard solutions were respectively prepared with dichloromethane, and the concentration of each was 1mg / mL. The above standard solutions were detected;

[0125] Detection result: 4-Trifluoromethoxyaniline and 3-trifluoromethoxyaniline completely overlapped, as specifically shown in Figure 5 shown.

[0126] Comparative Example 2

[0127] This comparative example provides a method for detecting related substances of 4-trifluoromethoxyaniline. Different from Example 1: The Merk Gamma DEX-225 chromatographic column was replaced with a capillary column with 2,6-di-O-pentyl-3-methoxy-β-cyclodextrin as the stationary liquid (B-DA chromatographic column, 30m * 0.25mm * 0.12μm), and other conditions were the same as those in Example 1;

[0128] Prepare standard solutions of trifluoromethoxybenzene, 2-trifluoromethoxyaniline, 3-trifluoromethoxyaniline, 4-trifluoromethoxyaniline, and p-nitrotrifluoromethoxybenzene in dichloromethane respectively, with a concentration of 1 mg / mL for each, and detect the above standard solutions;

[0129] Test results: 4-trifluoromethoxyaniline completely coincides with 3-trifluoromethoxyaniline, as specifically shown in Figure 6 the following.

[0130] The above-described embodiments are only preferred embodiments of the present invention and are not intended to limit the protection scope of the present invention. Any modifications, equivalent substitutions, or improvements made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A method for detecting related substances of 4-trifluoromethoxyaniline, characterized in that: The 4-trifluoromethoxyaniline-related substances include trifluoromethoxybenzene, p-nitrotrifluoromethoxybenzene, 2-trifluoromethoxyaniline and 3-trifluoromethoxyaniline, and are detected by gas chromatography, comprising the following steps: Preparation of test solution: Dissolve 4-trifluoromethoxyaniline sample in solvent to obtain test solution; Preparation of reference solution: dissolving trifluoromethoxybenzene reference substance, p-nitrotrifluoromethoxybenzene reference substance, 2-trifluoromethoxyaniline reference substance and 3-trifluoromethoxyaniline reference substance in a solvent to obtain a reference solution; The reference solution and the test solution are detected by gas chromatography, and the chromatographic conditions of the gas chromatography include: Chromatographic column: a capillary column using 2,3-di-O-acetyl-6-0-TBDMS-γ-cyclodextrin as the stationary phase; The heating program is as follows: starting temperature 38°C to 42°C, maintaining for 2 min to 4 min, heating to 195°C to 205°C at a rate of 8°C / min to 12°C / min, maintaining for 8 to 12 min; The injection port temperature is 195℃~205℃; The detector temperature is 245°C to 255°C.

2. The method for detecting related substances of 4-trifluoromethoxyaniline according to claim 1, characterized in that: The solvent is dichloromethane.

3. The method for detecting related substances of 4-trifluoromethoxyaniline according to claim 1, characterized in that: The specification of the chromatographic column is 30m×0.25mm, and the filler diameter is 0.25μm.

4. The method for detecting related substances of 4-trifluoromethoxyaniline according to claim 1 or 3, characterized in that: The chromatographic column is a Merk Gamma DEX-225 chromatographic column.

5. The method for detecting related substances of 4-trifluoromethoxyaniline according to claim 1, characterized in that: The concentration of 4-trifluoromethoxyaniline in the test solution is 8 mg / mL to 12 mg / mL.

6. The method for detecting related substances of 4-trifluoromethoxyaniline according to claim 1, characterized in that: The concentration of trifluoromethoxybenzene in the reference solution is 28 μg / mL to 30 μg / mL; and / or The concentration of p-nitrotrifluoromethoxybenzene in the reference solution is 28 μg / mL to 30 μg / mL.

7. The method for detecting related substances of 4-trifluoromethoxyaniline according to claim 1, characterized in that: The concentration of 2-trifluoromethoxyaniline in the reference solution is 28 μg / mL to 30 μg / mL; and / or The concentration of 3-trifluoromethoxyaniline in the reference solution is 28 μg / mL to 30 μg / mL.

8. The method for detecting related substances of 4-trifluoromethoxyaniline according to claim 1, characterized in that: The chromatographic conditions of the gas chromatography also include: the detector is a hydrogen flame ionization detector.

9. The method for detecting related substances of 4-trifluoromethoxyaniline according to claim 1, characterized in that: The chromatographic conditions of the gas chromatography method also include: a column flow rate of 1.8 mL / min to 2.2 mL / min.

10. The method for detecting related substances of 4-trifluoromethoxyaniline according to claim 1, characterized in that: The chromatographic conditions of the gas chromatography method also include: the injection volume is 0.8 μL to 1.2 μL; and / or The chromatographic conditions of the gas chromatography method also include: the split ratio is (5-15):1.

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