Method for detecting residual solvent in febuxostat bulk drug by GC (Gas Chromatography)

Abstract

According to the detection method for determining the residual solvent in the febuxostat bulk drug by GC, a specific chromatographic column is used for heating according to a program, and the chromatography has high separation efficiency; headspace sampling is used; taking a proper amount of a residual solvent reference substance, preparing a system applicability solution, and detecting the separation degree, the tailing factor and the number of theoretical plates by using the system applicability solution; the method comprises the following steps: taking a febuxostat bulk drug, precisely weighing the febuxostat bulk drug, placing the febuxostat bulk drug in a headspace bottle, precisely adding dimethyl sulfoxide, and sealing to obtain a test sample; taking a proper amount of residual solvent reference substances, precisely weighing, dissolving with dimethyl sulfoxide, quantitatively diluting, preparing a reference substance mixed solution with a certain concentration, precisely measuring the solution, putting into a headspace bottle, and sealing to obtain a reference substance sample; obtaining chromatograms of the test solution and the reference solution under qualified separation conditions, and quantitatively determining the amount of each residual solvent by an external standard method; through the steps, pretreatment of the sample and chromatographic analysis under specific conditions, the quality of the febuxostat bulk drug is ensured, and the safety of clinical medication is improved.

Description

Technical Field

[0001] The present invention discloses a technical field related to pharmaceutical detection, and relates to a detection method for residual solvents in febuxostat API by GC. Background Art

[0002] Hyperuricemia is the cause of various symptoms (gout arthritis and gout nodules) caused by urate deposition represented by gout. The higher the serum uric acid value, the higher the incidence of gout arthritis, and it can cause kidney damage. Therefore, it is more important to eliminate various symptoms caused by hyperuricemia early, prevent recurrence and disease progression, and more importantly, start treatment before symptoms appear. In addition, in recent years, as one of the lifestyle diseases, there have been more and more reports suggesting its association with hypertension and hyperlipidemia. It is a marker of metabolic syndrome and may also be a risk factor for arteriosclerosis. Therefore, the importance of its treatment is increasing.

[0003] The treatment of hyperuricemia mainly focuses on reducing uric acid. Since 1988, Teijin Limited (now Teijin Pharma Limited) has started research on uric acid-lowering drugs and discovered a novel xanthine oxidase inhibitor without a purine skeleton, febuxostat, in 1991. This product started phase I clinical trials in Japan in 1995, then phase II clinical trials, and successfully passed phase III clinical trials. In 2010, the long-term administration trial was completed, and a total of 1027 hyperuricemia patients including those with gout who were given this product were evaluated. The results confirmed the effectiveness and safety of this product for hyperuricemia patients including those with gout. In January 2011, this product was approved for marketing in Japan. The license holder is Teijin Pharma Limited, and the trade name is Feburic. The dosage form is tablets, and the specifications are 10mg, 20mg, and 40mg[1].[[]END]]

[0004] Febuxostat tablets were launched in the United States in February 2009 under the trade name ULORIC. The license holder is Takeda Pharmaceuticals USA Inc. The dosage form is tablets, and the specifications are 40mg and 80mg, with the status of RLD.

[0005] In the synthesis process of febuxostat API, alcohols, acetone, isopropanol, ethyl acetate, and N,N-dimethylformamide are used. Detecting the residual amounts of these solvents is very important for the safety of drug use. However, there is currently no good method to detect the residual amounts of these solvents, and it is impossible to ensure the quality of febuxostat API and thus guarantee the safety of clinical medication. Summary of the Invention

[0006] In view of this, the present application provides a method for detecting residual solvents in febuxostat raw materials by GC, through special steps, including sample pretreatment and chromatographic analysis under specific conditions.

[0007] According to one aspect of the present application, there is provided a method for detecting residual solvents in febuxostat raw materials by GC. The residual solvents are ethanol, acetone, isopropanol, ethyl acetate, and N,N-dimethylformamide. It is characterized by including sample pretreatment and chromatographic analysis under specific conditions, wherein: Step 1: Use a specific chromatographic column with programmed temperature rise, and the chromatography has high separation efficiency; Step 2: Use headspace injection; Step 3: Take appropriate amounts of reference substances of ethanol, acetone, isopropanol, ethyl acetate, and N,N-dimethylformamide to prepare a system suitability solution, and use the system suitability solution to detect the resolution, tailing factor, and theoretical plate number.

[0008] Step 4: Take febuxostat raw material, accurately weigh it, place it in a headspace vial, accurately add dimethyl sulfoxide, and seal it to obtain a test sample; Step 5: Take appropriate amounts of reference substances of ethanol, acetone, isopropanol, ethyl acetate, and N,N-dimethylformamide, accurately weigh them, dissolve them with dimethyl sulfoxide and quantitatively dilute to prepare a reference substance mixed solution with a certain concentration, and accurately measure this solution; Step 6: Obtain the chromatograms of the test solution and the reference solution under qualified separation conditions, and quantitatively determine the amounts of each residual solvent by the external standard method.

[0009] According to one aspect of the present application, take appropriate amounts of reference substances of ethanol, acetone, isopropanol, ethyl acetate, and N,N-dimethylformamide to prepare a system suitability solution, and use the system suitability solution to detect the resolution, tailing factor, and theoretical plate number. The resolution between each component peak should be greater than 1.5, the tailing factor should be between 0.8 and 1.2, and the theoretical plate number of each peak should not be less than 3000.

[0010] According to one aspect of the present application, take febuxostat raw material, accurately weigh it, place it in a headspace vial, accurately add dimethyl sulfoxide, and seal it to obtain a test sample. Take 0.1 g of febuxostat raw material and accurately add 1 ml of dimethyl sulfoxide.

[0011] According to one aspect of the present application, take appropriate amounts of reference substances of ethanol, acetone, isopropanol, ethyl acetate, and N,N-dimethylformamide, accurately weigh them, dissolve them with dimethyl sulfoxide and quantitatively dilute to prepare a mixed solution containing about 0.5 mg of ethanol, 0.5 mg of acetone, 0.5 mg of isopropanol, 0.5 mg of ethyl acetate, and 0.088 mg of N,N-dimethylformamide per 1 ml. Accurately measure 1 ml and place it in a headspace vial, and seal it to obtain a reference sample.

[0012] According to one aspect of the present application, the chromatographic column for gas chromatography detection is a capillary column with 6% cyanopropylphenyl - 94% dimethylpolysiloxane as the stationary liquid.

[0013] According to one aspect of the present application, the gas chromatography detection is a programmed temperature rise. The initial temperature is 40°C and it is maintained for 5 minutes; then it is heated at a rate of 10°C per minute to 90°C and maintained for 2 minutes, and then heated at a rate of 50°C per minute to 230°C and maintained for 5 minutes; the inlet temperature is maintained at 200°C.

[0014] According to one aspect of the present application, the flow rate of the mobile phase for the liquid chromatography detection is 0.8 - 1.2 ml / min, and the split ratio is 20:1 - 5.

[0015] According to one aspect of the present application, the liquid-gas detector is a flame ionization detector.

[0016] Advantages of the present invention: Through the above steps, the pretreatment of the sample and chromatographic analysis under specific conditions can detect the residues of ethanol, acetone, isopropanol, ethyl acetate and N, N-dimethylformamide in the febuxostat raw material drug. It has the advantages of strong specificity, high sensitivity and good precision, ensuring the quality of the febuxostat raw material drug and improving the safety of clinical medication. Description of the Drawings

[0017] Figure 1 Shows the chromatogram of the system suitability solution of Example 1 of the present application;

[0018] Figure 2 Shows the chromatogram of the system suitability solution of Example 2 of the present application;

[0019] Figure 3 Shows the chromatogram of the system suitability solution of Example 3 of the present application;

[0020] Figure 4 Shows the chromatogram of the test solution of the present application. Detailed Embodiments

[0021] The following embodiments are provided to better understand the present invention further. It is not limited to the best embodiment, and does not limit the content and protection scope of the present invention. Any product that is the same as or similar to the present invention obtained by anyone under the inspiration of the present invention or by combining the features of the present invention with other prior art features falls within the protection scope of the present invention.

[0022] For those where specific experimental steps or conditions are not indicated in the embodiments, the operations or conditions of the conventional experimental steps described in the literature in this field can be followed. For the reagents or instruments whose manufacturers are not indicated, they are all conventional reagent products that can be obtained through commercial purchase.

[0023] According to one aspect of the present application, a detection method for residual solvents in febuxostat raw material by GC is provided. The residual solvents are ethanol, acetone, isopropanol, ethyl acetate and N, N-dimethylformamide. It is characterized in that it includes pretreatment of the sample and chromatographic analysis under specific conditions, wherein: Step 1: Use a specific chromatographic column with a programmed temperature rise, and the chromatography has high separation efficiency; Step 2: Use headspace injection; Step 3: Take appropriate amounts of reference substances of ethanol, acetone, isopropanol, ethyl acetate and N, N-dimethylformamide to prepare a system suitability solution, and use the system suitability solution to detect the resolution, tailing factor and theoretical plate number; Step 4: Take febuxostat raw material, weigh it precisely, place it in a headspace bottle, precisely add dimethyl sulfoxide, and seal it to obtain a test sample; Step 5: Take appropriate amounts of reference substances of ethanol, acetone, isopropanol, ethyl acetate and N, N-dimethylformamide, weigh them precisely, dissolve them with dimethyl sulfoxide and quantitatively dilute to prepare a reference substance mixed solution with a certain concentration, and precisely measure this solution; Step 6: Obtain the chromatograms of the test sample solution and the reference substance solution under qualified separation conditions, and quantify by the external standard method to determine the amounts of each residual solvent.

[0024] Preferably, in Step 2: Use headspace injection, which can avoid the interference of non-volatile substances on chromatographic detection.

[0025] Furthermore, take appropriate amounts of reference substances of ethanol, acetone, isopropanol, ethyl acetate and N, N-dimethylformamide to prepare a system suitability solution, and use the system suitability solution to detect the resolution, tailing factor and theoretical plate number. The resolution between each component peak should be greater than 1.5, the tailing factor should be between 0.8 and 1.2, and the theoretical plate number of each peak should not be less than 3000.

[0026] In an achievable embodiment, take febuxostat raw material, weigh it precisely, place it in a headspace bottle, precisely add dimethyl sulfoxide, and seal it to obtain a test sample. And take 0.1 g of febuxostat raw material and precisely add 1 ml of dimethyl sulfoxide.

[0027] Furthermore, take appropriate amounts of reference substances of ethanol, acetone, isopropanol, ethyl acetate and N, N-dimethylformamide, weigh them precisely, dissolve them with dimethyl sulfoxide and quantitatively dilute to prepare a mixed solution containing about 0.5 mg of ethanol, 0.5 mg of acetone, 0.5 mg of isopropanol, 0.5 mg of ethyl acetate and 0.088 mg of N, N-dimethylformamide per 1 ml. Precisely measure 1 ml and place it in a headspace bottle, and seal it to obtain a reference substance sample.

[0028] In an achievable embodiment, the chromatographic column for gas chromatography detection is a capillary column with 6% cyanopropylphenyl-94% dimethylpolysiloxane as the stationary liquid.

[0029] In one possible embodiment, the gas chromatography detection is a programmed temperature rise, starting at 40 °C and maintaining for 5 minutes; heating at a rate of 10 °C per minute to 90 °C and maintaining for 2 minutes, then heating at a rate of 50 °C per minute to 230 °C and maintaining for 5 minutes; the inlet temperature is maintained at 200 °C.

[0030] Furthermore, the flow rate of the mobile phase for the gas chromatography detection is 0.8 - 1.2 ml / min, and the split ratio is 20:1 - 5.

[0031] Preferably, the flow rate of the mobile phase can be 0.8 ml / min, 0.9 ml / min, 1.0 ml / min, 1.1 ml / min or 1.2 ml / min.

[0032] According to one aspect of the present application, the liquid-gas detector is a flame ionization detector.

[0033] Example 1

[0034] A method for determining the residues of ethanol, acetone, isopropanol, ethyl acetate and N, N-dimethylformamide in febuxostat API by GC includes the following steps:

[0035] Step 1: Prepare the system suitability solution: Take appropriate amounts of ethanol, acetone, isopropanol, ethyl acetate and N, N-dimethylformamide, accurately weigh them, dissolve with dimethyl sulfoxide and quantitatively dilute to prepare a mixed solution containing about 0.5 mg of ethanol, 0.5 mg of acetone, 0.5 mg of isopropanol, 0.5 mg of ethyl acetate and 0.088 mg of N, N-dimethylformamide per 1 ml. Accurately measure 1 ml and place it in a headspace vial, then seal it; use the system suitability solution to detect the resolution, tailing factor and theoretical plate number. Among them, the resolution between the chromatographic peaks of each residual solvent should be greater than 1.5, the tailing factor should be between 0.8 - 1.2, and the theoretical plate number should not be less than 3000;

[0036] Step 2: Prepare the test solution: Take about 0.1 g of the test sample, accurately weigh it, place it in a headspace vial, and accurately add 1 ml of dimethyl sulfoxide, then seal it;

[0037] Step 3: Prepare the reference solution: Use the same preparation method as the system suitability solution;

[0038] Step 4: Obtain the chromatograms of the test solution and the reference solution under qualified chromatographic separation conditions, and determine the residue amounts of each solvent by the external standard method;

[0039] In this example, the solvents described in the above Step 1, Step 2 and Step 3 are dimethyl sulfoxide;

[0040] Chromatographic conditions:

[0041] Chromatographic column: A capillary column with 6% cyanopropylphenyl - 94% dimethylpolysiloxane as the stationary phase is used as the chromatographic column (DB624, 60 m × 0.32 mm, 1.8 μm or a chromatographic column with equivalent efficiency); FID detector, flow rate: 1.0 ml / min, inlet temperature: 200 °C, detector temperature: 250 °C, split ratio 20:1, carrier gas: nitrogen; headspace injection mode, headspace equilibrium temperature 80 °C, sample equilibrium time 30 minutes, quantitative loop temperature: 90 °C; transfer line temperature: 100 °C. Column temperature program: The initial temperature is 40 °C, maintained for 5 minutes, heated at a rate of 10 °C per minute to 90 °C, maintained for 2 minutes, and then heated at a rate of 150 °C per minute to 230 °C, maintained for 5 minutes.

[0042] Example 2

[0043] A method for determining the residues of ethanol, acetone, isopropanol, ethyl acetate and N,N - dimethylformamide in febuxostat API by GC, comprising the following steps:

[0044] Step 1: Prepare the system suitability solution: Take appropriate amounts of ethanol, acetone, isopropanol, ethyl acetate and N,N - dimethylformamide, accurately weigh, dissolve with dimethyl sulfoxide and quantitatively dilute to prepare a mixed solution containing about 0.5 mg of ethanol, 0.5 mg of acetone, 0.5 mg of isopropanol, 0.5 mg of ethyl acetate and 0.088 mg of N,N - dimethylformamide per 1 ml. Accurately measure 1 ml and transfer it to a headspace vial, then seal it. Use the system suitability solution to detect the resolution, tailing factor and theoretical plate number. Among them, the resolution between the chromatographic peaks of each residual solvent should be greater than 1.5, the tailing factor should be between 0.8 - 1.2, and the theoretical plate number should not be less than 3000;

[0045] Step 2: Prepare the test solution: Take about 0.1 g of the test sample, accurately weigh, transfer it to a headspace vial, accurately add 1 ml of dimethyl sulfoxide, and seal it;

[0046] Step 3: Prepare the reference solution: The same method as for preparing the system suitability solution;

[0047] Step 4: Obtain the chromatograms of the test solution and the reference solution under qualified chromatographic separation conditions, and determine the residues of each solvent by the external standard method;

[0048] In this example, the solvents described in the above Step 1, Step 2 and Step 3 are dimethyl sulfoxide;

[0049] Chromatographic conditions:

[0050] Chromatographic column: A capillary column with 6% cyanopropylphenyl - 94% dimethylpolysiloxane as the stationary liquid is used as the chromatographic column (DB624, 60 m × 0.32 mm, 1.8 μm or a chromatographic column with equivalent efficiency); FID detector, flow rate: 1.0 ml / min, inlet temperature: 200 °C, detector temperature: 250 °C, split ratio 10:1, carrier gas: nitrogen; headspace injection mode, headspace equilibrium temperature 80 °C, sample equilibrium time 30 minutes, quantitative loop temperature: 90 °C; transfer line temperature: 100 °C. Column temperature program: The initial temperature is 40 °C, maintained for 5 minutes, heated at a rate of 10 °C per minute to 90 °C, maintained for 2 minutes, and then heated at a rate of 150 °C per minute to 230 °C, maintained for 5 minutes.

[0051] Example 3

[0052] A method for determining the residues of ethanol, acetone, isopropanol, ethyl acetate and N,N - dimethylformamide in febuxostat API by GC, comprising the following steps:

[0053] Step 1: Prepare the system suitability solution: Take appropriate amounts of ethanol, acetone, isopropanol, ethyl acetate and N,N - dimethylformamide, accurately weigh them, dissolve with dimethyl sulfoxide and quantitatively dilute to prepare a mixed solution containing about 0.5 mg of ethanol, 0.5 mg of acetone, 0.5 mg of isopropanol, 0.5 mg of ethyl acetate and 0.088 mg of N,N - dimethylformamide per 1 ml. Accurately measure 1 ml and transfer it into a headspace vial, then seal it. Use the system suitability solution to detect the resolution, tailing factor and theoretical plate number. The resolution between the chromatographic peaks of each residual solvent should be greater than 1.5, the tailing factor should be between 0.8 - 1.2, and the theoretical plate number should not be less than 3000 for all.

[0054] Step 2: Prepare the test solution: Take about 0.1 g of the test sample, accurately weigh it, transfer it into a headspace vial, accurately add 1 ml of dimethyl sulfoxide, and then seal it.

[0055] Step 3: Prepare the reference solution: Follow the same preparation method as the system suitability solution.

[0056] Step 4: Obtain the chromatograms of the test solution and the reference solution under qualified chromatographic separation conditions, and determine the residues of each solvent by the external standard method.

[0057] In this example, the solvents mentioned in the above Step 1, Step 2 and Step 3 are dimethyl sulfoxide.

[0058] Chromatographic conditions:

[0059] Chromatographic column: A capillary column with 6% cyanopropylphenyl - 94% dimethylpolysiloxane as the stationary phase is used as the chromatographic column (DB624, 60 m × 0.32 mm, 1.8 μm or a chromatographic column with equivalent performance); FID detector, flow rate: 1.0 ml / min, inlet temperature: 200 °C, detector temperature: 250 °C, split ratio 20:1, carrier gas: nitrogen; headspace injection mode, headspace equilibrium temperature 100 °C, sample equilibrium time 30 minutes, quantitative loop temperature: 90 °C; transfer line temperature: 100 °C. Column temperature program: The initial temperature is 40 °C, maintained for 5 minutes, heated at a rate of 10 °C per minute to 90 °C, maintained for 2 minutes, and then heated at a rate of 150 °C per minute to 230 °C, maintained for 5 minutes.

[0060] Table 1 shows the system suitability results under the chromatographic conditions of Example 1:

[0061]

[0062] Table 2 shows the system suitability results under the chromatographic conditions of Example 2:

[0063]

[0064] Table 3 shows the system suitability results under the chromatographic conditions of Example 3:

[0065]

[0066]

[0067] Table 4 shows the test results of febuxostat API (batch number: FA230909A) under these chromatographic conditions:

[0068] Ethanol (%) Acetone (%) Isopropanol (%) Ethyl acetate (%) N,N-Dimethylformamide (%) 0.003 ＜0.00025 0.01 ＜0.00025 ＜0.0044

[0069] It can be seen that through the steps and various defined values of Examples 1, 2, and 3, the residual amounts of ethanol, acetone, isopropanol, ethyl acetate, and N,N - dimethylformamide in febuxostat API can be accurately detected by GC.

[0070] In this application, by using a specific chromatographic column with a programmed temperature rise, the chromatography has high separation efficiency; headspace injection is used. Appropriate amounts of ethanol, acetone, isopropanol, ethyl acetate, and N,N-dimethylformamide reference substances are taken to prepare a system suitability solution, and the resolution, tailing factor, and theoretical plate number are detected with the system suitability solution. Take febuxostat raw material medicine, weigh it precisely, place it in a headspace vial, precisely add dimethyl sulfoxide, and seal it to obtain a test sample; take appropriate amounts of ethanol, acetone, isopropanol, ethyl acetate, and N,N-dimethylformamide reference substances, weigh them precisely, dissolve them with dimethyl sulfoxide and quantitatively dilute them, mix them with N,N-dimethylformamide, precisely measure them, place them in a headspace vial, and seal it to obtain a reference sample; obtain the chromatograms of the test solution and the reference solution under qualified separation conditions, and quantitatively determine the amounts of each residual solvent by the external standard method. Through the sample pretreatment and chromatographic analysis under specific conditions in the above steps, the detection of the residues of ethanol, acetone, isopropanol, ethyl acetate, and N,N-dimethylformamide in febuxostat raw material medicine can be carried out, which has the advantages of strong specificity, high sensitivity, and good precision, ensuring the quality of febuxostat raw material medicine and thus improving the safety of clinical medication, and solving the technical problems that there is no good method to detect the residue amounts of these solvents, unable to ensure the quality of febuxostat raw material medicine and thus illegally ensuring the safety of clinical medication.

[0071] As described above, it is only the preferred specific embodiment of the present invention, but the protection scope of the present invention is not limited thereto. Any person skilled in the art within the scope disclosed by the present invention, according to the technical solution and its concept of the present invention, makes equivalent substitutions or changes, and all should be covered within the protection scope of the present invention.

Claims

1. A GC method for determining residual solvents in Febuxostat API, wherein the residual solvents are ethanol, acetone, isopropanol, ethyl acetate and N,N-dimethylformamide, characterized in that: It includes sample pretreatment and chromatographic analysis under specific conditions, including: Step 1: Use a specific chromatographic column and increase the temperature according to a program. Chromatography has high separation efficiency. Step 2: Use headspace injection; Step 3: Take appropriate amounts of ethanol, acetone, isopropanol, ethyl acetate and N,N-dimethylformamide reference substance to prepare a system suitability solution, and use the system suitability solution to test the resolution, tailing factor and theoretical plate number; Step 4: Take the Febuxostat API, weigh it accurately, place it in an empty bottle, accurately add dimethyl sulfoxide, seal it, and use it as the test sample; Step 5: Take appropriate amounts of ethanol, acetone, isopropanol, ethyl acetate and N,N-dimethylformamide reference substance, accurately weigh them, dissolve them with dimethyl sulfoxide and quantitatively dilute them to prepare a reference substance mixed solution of a certain concentration, accurately measure the solution, place it in an empty bottle, and seal it as a reference substance sample; Step 6: Obtain chromatograms of the test solution and the reference solution under qualified separation conditions, and quantitatively determine the amount of each residual solvent by external standard method.

2. The method for detecting residual solvents in Febuxostat bulk drug by GC according to claim 1, characterized in that: Take appropriate amounts of ethanol, acetone, isopropanol, ethyl acetate and N,N-dimethylformamide reference substance to prepare system suitability solution. Use the system suitability solution to detect the separation, tailing factor and theoretical plate number. The separation between the peaks of each component should be greater than 1.5, the tailing factor should be between 0.8-1.2, and the theoretical plate number of each peak should not be less than 3000.

3. The method for detecting residual solvents in Febuxostat bulk drug by GC according to claim 2, characterized in that: Take the Febuxostat API, accurately weigh it, place it in an empty bottle, accurately add dimethyl sulfoxide, seal it, and use it as the test sample. Take 0.1 g of the Febuxostat API and accurately add 1 ml of dimethyl sulfoxide.

4. The method for detecting residual solvents in Febuxostat bulk drug by GC according to claim 3, characterized in that: Take appropriate amounts of ethanol, acetone, isopropanol, ethyl acetate and N,N-dimethylformamide reference substances, accurately weigh them, dissolve them with dimethyl sulfoxide and quantitatively dilute them to make a mixed solution containing approximately 0.5 mg of ethanol, 0.5 mg of acetone, 0.5 mg of isopropanol, 0.5 mg of ethyl acetate and 0.088 mg of N,N-dimethylformamide per 1 ml. Accurately measure 1 ml, place it in an empty bottle, and seal it as a reference sample.

5. The method for detecting residual solvents in Febuxostat bulk drug by GC according to claim 4, characterized in that: The chromatographic column for gas chromatography detection is a capillary column with 6% cyanopropylphenyl-94% dimethylpolysiloxane as the stationary liquid.

6. The method for detecting residual solvents in Febuxostat bulk drug by GC according to claim 5, characterized in that: The gas chromatography detection is programmed temperature rising, starting at 40°C and maintained for 5 minutes; heating to 90°C at a rate of 10°C per minute, maintained for 2 minutes, and then heating to 230°C at a rate of 50°C per minute, maintained for 5 minutes; the injection port temperature is maintained at 200°C.

7. The method for detecting residual solvents in Febuxostat API by GC according to claim 6, characterized in that: The flow rate of the mobile phase for gas chromatography detection is 0.8-1.2 ml / min, and the split ratio is 20:1-5.

8. The method for detecting residual solvents in Febuxostat bulk drug by GC according to claim 8, characterized in that: The liquid-gas phase detector is a flame ionization detector.

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