WO2022151842A1 - Gas-phase chromatography detection method for dicyclohexylamine in favipiravir - Google Patents

Abstract

A gas-phase detection method for dicyclohexylamine in favipiravir that has a short analysis time, high sensitivity and good reproducibility. A 30% sodium hydroxide solution that has a mass percentage concentration unit of g/g is used, heated and set aside, so that the interference of a matrix on a detection substance dicyclohexylamine may be eliminated with good linearity and quantitative accuracy. Adding the 30% sodium hydroxide solution may eliminate the reaction and adsorption of phenolic hydroxyl groups on the detection substance. Once a sample is treated by adding alkali and set aside, the sample is injected. The results are accurate and reproducible.

Description

A kind of gas chromatography detection method of dicyclohexylamine in favipiravir technical field

The invention relates to the field of chemical analysis and detection, in particular to a gas chromatography detection method for the content of dicyclohexylamine in favipiravir.

Background technique

Favipiravir (T-705), whose chemical name is 6-fluoro-3-hydroxypyrazine-2-carboxamide, is a novel RNA-dependent RNA polymerase (RdRp) inhibitor class of broad-spectrum antiviral drugs. It has a good therapeutic effect on influenza A (including avian influenza and influenza A H1N1 infection) virus, and its structural formula is as follows

The dicyclohexylamine used in the synthetic route of favipiravir is a flammable and highly toxic substance. It is very important to accurately and rapidly quantitatively detect these toxic substances in the production process so as to effectively remove them in the product. Control product quality. The conventional gas chromatographic detection method of dicyclohexylamine content in favipiravir has problems such as low recovery rate of dicyclohexylamine after being dissolved in organic solvent and then injected.

SUMMARY OF THE INVENTION

In order to overcome the problem of low recovery rate of dicyclohexylamine in conventional gas chromatography detection methods, the invention provides a gas chromatography detection method for dicyclohexylamine in favipiravir with short analysis time, high sensitivity and good reproducibility .

A gas chromatography detection method of dicyclohexylamine in favipiravir, which is realized by the following scheme, the detection sample in the gas chromatography detection is pretreated by adding sodium hydroxide solution, and the sodium hydroxide solution is a mass percentage The concentration unit is g/g of 30% sodium hydroxide aqueous solution, and the pretreatment is heating at 80° C. for 1 h.

Further, in the gas chromatography detection method of dicyclohexylamine in favipiravir, the concentration of dicyclohexylamine in the detection sample in the detection sample is 4ppm-30ppm.

Further, a gas chromatographic detection method of dicyclohexylamine in favipiravir, comprising the following steps:

1) Preparation of standard samples: take dicyclohexylamine, add diluent N,N dimethylacetamide to dissolve, and configure it into a linear dicyclohexylamine reference solution with a linear concentration range; take the linear dicyclohexylamine reference solution respectively In the injection bottle, add 30% sodium hydroxide solution with a mass percentage concentration unit of g/g, mix well, seal and shake;

2) Preparation of test samples: Weigh the favipiravir sample, add diluent N,N dimethylacetamide to dissolve, then add 30% sodium hydroxide solution to mix, seal and shake; heat at 80°C for 1 hour, take out and cool To room temperature, centrifuge to take the supernatant, transfer the supernatant to the injection bottle; wait for the injection to detect;

3) Gas chromatographic detection: carry out gas chromatographic detection with the above-mentioned standard sample and the detection sample, take the concentration of the linear control solution as the abscissa and the peak area as the ordinate, and draw the standard curve of the linear equation; calculate the bicyclic ring in favipiravir by the external standard method Hexylamine content.

Further, the detection limit concentration of the dicyclohexylamine is 0.096 μg/ml.

Further, the concentration range of the linear dicyclohexylamine control solution in the step (1) is: 0.32 μg/ml～3.20 μg/ml; in the step (1), the linear dicyclohexylamine control solution and 30% hydrogen The volume ratio of sodium oxide is 20:3.

Further, in described step (2), the weight volume ratio of favipiravir sample and N,N dimethylacetamide is 80:1, unit mg/ml; described N,N dimethylacetamide and 30 The volume ratio of % sodium hydroxide is 20:3.

Further, the chromatographic column detected by gas chromatography in the step (3) is: Agilent HP-5 gas chromatographic column, and the stationary phase is (5%-phenyl)-methyl polysiloxane, specification: 30m×0.53 mm × 5.00 μm, and the carrier gas is nitrogen.

Further, the conditions for gas chromatography detection in the step (3) are: flow rate 3.5～4.5ml/min, initial column temperature 35°C～45°C, split ratio 0.8:1～1.2:1; temperature program: 40°C Hold for 3min, heat up to 200°C at 10°C/min, hold for 5min; heat up to 220°C at 20°C/min, hold for 10min.

As a further preference, the gas chromatography conditions in the step (3) are: the flow rate is 4.0ml/min, the initial column temperature is 40°C, and the split ratio is 1:1.

The difficulty of gas chromatography detection of dicyclohexylamine in favipiravir samples is: the concentration of dicyclohexylamine control solution is low, and the corresponding signal is weak; the matrix in the sample in favipiravir sample solution will affect the volatilization of dicyclohexylamine analyze. The invention adopts 30% sodium hydroxide solution with mass percentage concentration unit of g/g as pretreatment, which can eliminate the interference of the matrix on the detection substance dicyclohexylamine, has good linearity and accurate quantification; at the same time, there are phenolic hydroxyl groups in the favipiravir structure , it has a reactive adsorption effect on the test substance dicyclohexylamine, which will cause inaccurate test results; adding 30% sodium hydroxide solution can eliminate the reactive adsorption effect of phenolic hydroxyl groups on the test substance. Accurate and reproducible.

Description of drawings

Fig. 1 is a graph of the linear equation standard curve in the preparation example of the standard curve of the present invention.

Fig. 2 is the superimposed spectrum of the dicyclohexylamine control solution, blank solution, sample solution and sample spiked solution in the comparative example of the present invention.

FIG. 3 is the superimposed spectrum of the dicyclohexylamine control solution, blank solution, sample solution and sample spiked solution in Example 1 of the present invention.

Detailed ways

The gas chromatographic detection instrument used in the present invention is: Agilent 7890 gas chromatograph.

The gas chromatography column and chromatographic conditions used are: Agilent HP-5 gas chromatography column, stationary phase is (5%-phenyl)-methyl polysiloxane, size: 30m×0.53mm×5.00μm, carrier gas is nitrogen ; Chromatographic conditions are carrier gas flow rate: 4.0 ml/min, split ratio: 1:1, injection volume: 3.0 μl, and injection port temperature: 250°C.

Detector temperature: 300°C/hydrogen flame ionization detector (FID).

Column temperature: hold at 40°C for 3 minutes, raise the temperature to 200°C at 10°C/min and hold for 5 minutes; raise the temperature at 20°C/min to 220°C and hold for 10 minutes.

The standard used is: dicyclohexylamine, AR reagent of Sinopharm Chemical Reagent Co., Ltd.

Diluent: N,N dimethylacetamide, TEDIA chemical reagent.

Preparation of 30% sodium hydroxide solution: Weigh 30g of sodium hydroxide, add 70g of water to dissolve and mix.

Determination of recovery rate of dicyclohexylamine: Weigh 80 mg of favipiravir sample, add 1.0 ml of dicyclohexylamine control solution to dissolve, add 150 μl of 30% sodium hydroxide solution with a mass percentage concentration unit of g/g, mix well, seal and shake After shaking for 1 min, place it in an oven at 80°C for 1 h; after taking it out and placing it at room temperature, transfer the liquid to a direct injection bottle; centrifuge for 10 min at 1000 r/min, and take the supernatant for injection.

Example of standard curve preparation:

Chromatographic conditions: Agilent HP-5 gas chromatography column, stationary phase is (5%-phenyl)-methyl polysiloxane, size: 30m×0.53mm×5.00μm, flow rate is 4.0ml/min, split ratio is 1 : 1; programmed temperature rises to 40°C for 3min, 10°C/min to 200°C and hold for 5min; 20°C/min to 220°C for 10min;

The diluent is N,N dimethylacetamide;

Preparation of linear dicyclohexylamine solution: take 16mg of dicyclohexylamine, accurately weigh and place it in a 100ml volumetric flask, dissolve and dilute to the mark with diluent, and mix well; accurately transfer 2.0ml into a 100ml volumetric flask, and dilute with diluent to scale, and mix well; then precisely pipette 2.0ml, 5.0ml, 8.0ml, 10.0ml, and 15.0ml into four 20ml volumetric flasks, dilute to the mark with diluent, and mix well; obtain 0.32, 0.80, and 1.28 , 1.60, 2.40, 3.20 μg/ml linear solutions; precisely pipette 1.0 ml of each linear solution into the injection bottle, then add 150 μl of 30% sodium hydroxide solution to mix well, take the linear solution concentration as the abscissa and the peak area as the vertical Coordinates, draw the standard curve of the linear equation.

Quantitative limit solution: Precisely pipette 1.0ml of 0.32μg/ml linear solution into the injection bottle, then add 150μl of 30% sodium hydroxide solution and mix well.

Detection limit solution: Precisely pipette 3.0ml of 0.32μg/ml linear solution into a 10ml volumetric flask, dilute to the mark with diluent, and mix well; then take 1.0ml into the injection bottle, and then add 150μl of 30% sodium hydroxide solution Mix well.

Result: The linear equation is y=21.5418x-0.7581, and the correlation coefficient is 0.9990. See Table 1 and Figure 1 for details.

Table 1 Dicyclohexylamine standard curve

Concentration (μg/ml)	Peak area
0.32	7.04866
0.80	15.78306
1.28	25.82713
1.60	34.19762
2.40	51.12500
3.20	68.27133

The S/N ratios of dicyclohexylamine in the quantification limit solution were 20.1, 17.9, 18.8, 17.8, 18.1, 19.3.

The S/N ratios of dicyclohexylamine in the detection limit solution were 5.9 and 3.8.

Recycling Example

Chromatographic conditions: Agilent HP-5 gas chromatography column, stationary phase is (5%-phenyl)-methyl polysiloxane, size: 30m×0.53mm×5.00μm, flow rate is 4.0ml/min, split ratio is 1 : 1; programmed temperature rises to 40°C for 3min, 10°C/min to 200°C and hold for 5min; 20°C/min to 220°C for 10min;

Dicyclohexylamine sample recovery experiment: Weigh 80 mg of favipiravir sample, add 1.0 ml of dicyclohexylamine solution with dicyclohexylamine content of 0.32 μg/ml, 1.60 μg/ml, 2.40 μg/ml N-dimethylacetamide was dissolved as a diluent); then 150 μl of 30% sodium hydroxide solution was added to mix, sealed and shaken; heated at 80°C for 1 h, taken out and placed at room temperature, then pipetted the liquid into a sample bottle; centrifuged The supernatant was taken and injected; 3 copies were prepared for each concentration. The experimental design and results are shown in Table 2.

Table 2 Dicyclohexylamine recovery rate

Analysis of the recovery rate data shows that: the concentration of dicyclohexylamine in the added sample is 0.32 μg/ml (equivalent to 4ppm of the concentration of the sample solution), and the average recovery rate is 82.63%; the concentration of dicyclohexylamine in the added sample is 1.60 μg/ml (equivalent to 20ppm of the sample solution concentration), the average recovery rate is 91.66%; adding the dicyclohexylamine concentration in the sample 2.40μg/ml (equivalent to 30ppm of the sample solution concentration), the average recovery rate is 82.37%. Among them, 1ppm is equivalent to 1 μg/g, which means that each g of favipiravir contains 1 μg of dicyclohexylamine.

Comparative ratio:

Chromatographic conditions: Agilent HP-5 gas chromatography column, stationary phase is (5%-phenyl)-methyl polysiloxane, size: 30m×0.53mm×5.00μm, flow rate is 4.0ml/min, split ratio is 1 : 1; programmed temperature rises to 40°C for 3min, 10°C/min to 200°C for 12min; diluent: N,N dimethylacetamide;

Dicyclohexylamine control solution: prepare 1.6μg/ml dicyclohexylamine control solution;

Sample solution: Weigh 80 mg of favipiravir sample and add 1.0 ml of diluent N,N dimethylacetamide to dissolve and mix;

Dicyclohexylamine sample recovery experiment: Weigh 80 mg of favipiravir sample, add 1.0 ml of 1.60 μg/ml dicyclohexylamine control solution to dissolve and mix;

Results: The recovery rate of dicyclohexylamine was only 50%; it indicated that favipiravir was injected after using the diluent solution, and the sample matrix had an influence on the recovery rate of dicyclohexylamine; the limit of dicyclohexylamine was low, and the interference of the sample matrix was large, see Figure 2.

Example 1

Chromatographic conditions: Agilent HP-5 gas chromatography column, stationary phase is (5%-phenyl)-methyl polysiloxane, size: 30m×0.53mm×5.00μm, flow rate is 4.0ml/min, split ratio is 1 : 1; programmed temperature rises to 40°C for 3min, 10°C/min to 200°C for 12min; diluent: N,N dimethylacetamide;

Dicyclohexylamine control solution: prepare 1.6μg/ml dicyclohexylamine solution, take 1.0ml into the injection bottle, then add 100μl of 30% sodium hydroxide solution and mix well;

Sample solution: Weigh 80 mg of favipiravir sample, add 1.0 ml of diluent N,N dimethylacetamide to dissolve, and then add 100 μl of 30% sodium hydroxide solution to mix well. After shaking, a large amount of solid precipitates out. clear liquid injection;

Dicyclohexylamine sample recovery experiment: Weigh 80 mg of favipiravir sample, add 1.0 ml of dicyclohexylamine control solution to dissolve; then add 100 μl of 30% sodium hydroxide solution and mix well. Take the supernatant for injection.

Results: The recovery rate of dicyclohexylamine was 89%; it was shown that the sample solution was treated with alkali solution, and the recovery rate of dicyclohexylamine was obviously improved, as shown in Figure 3.

Embodiment 2: compare the volume of adding lye, stand time, stand temperature parameter comparison

Chromatographic conditions Agilent HP-5 gas chromatography column, stationary phase is (5%-phenyl)-methyl polysiloxane, size: 30m×0.53mm×5.00μm, flow rate is 4.0ml/min, split ratio is 1: 1; Program temperature at 40°C for 3min, 10°C/min to 200°C, hold for 12min; diluent: N,N dimethylacetamide;

The first group: Dicyclohexylamine control solution: prepare 1.6μg/ml dicyclohexylamine solution; take 1.0ml of this solution, add 60mg solid NaOH, seal and shake;

Sample solution: Weigh 80 mg of favipiravir sample, add 1.0 ml of N,N dimethylacetamide to dissolve; add 60 mg of solid NaOH, seal and shake;

Dicyclohexylamine sample recovery solution: Weigh 80 mg of favipiravir sample, add 1.0 ml of dicyclohexylamine control solution to dissolve; add and weigh 60 mg of solid NaOH, seal and shake.

The second group: Dicyclohexylamine control solution: prepare 1.6μg/ml dicyclohexylamine solution; take 1.0ml of this solution and add 100μL of 30% NaOH solution, seal and shake;

Sample solution: Weigh 80 mg of favipiravir sample, add 1.0 ml of N,N dimethylacetamide to dissolve; add 100 μL of 30% NaOH solution, seal and shake, centrifuge to take the supernatant for injection;

Dicyclohexylamine sample recovery solution: Weigh 80 mg of favipiravir sample, add 1.0 ml of dicyclohexylamine control solution to dissolve; add 100 μL of 30% NaOH solution, seal and shake, centrifuge to take the supernatant for injection.

The third group: Dicyclohexylamine control solution: prepare 1.6μg/ml dicyclohexylamine solution; take 1.0ml of this solution and add 200μL of 30% NaOH solution, seal and shake;

Sample solution: Weigh 80 mg of favipiravir sample, add 1.0 ml of N,N dimethylacetamide to dissolve; add 200 μL of 30% NaOH solution, seal and shake, and centrifuge to take the supernatant for injection;

Dicyclohexylamine sample recovery solution: Weigh 80 mg of favipiravir sample, add 1.0 ml of dicyclohexylamine control solution to dissolve; add 200 μL of 30% NaOH solution, seal and shake, and centrifuge to take the supernatant for injection.

Group 4: Dicyclohexylamine control solution: prepare 1.6μg/ml dicyclohexylamine solution; take 1.0ml of this solution, add 150μL of 30% NaOH solution, seal and shake;

Sample solution: Weigh 80 mg of favipiravir sample, add 1.0 ml of N,N dimethylacetamide to dissolve; add 150 μL of 30% NaOH solution, seal and shake, and place overnight at room temperature without centrifugation;

Dicyclohexylamine sample recovery solution: Weigh 80 mg of favipiravir sample, add 1.0 ml of dicyclohexylamine control solution to dissolve; add 150 μL of 30% NaOH solution, seal and shake, and place overnight at room temperature without centrifugation.

Group 5: Dicyclohexylamine control solution: prepare 1.6μg/ml dicyclohexylamine solution; take 1.0ml of this solution, add 150μL of 30% NaOH solution, seal and shake;

Sample solution: Weigh 80 mg of favipiravir sample, add 1.0 ml of N,N dimethylacetamide to dissolve; add 150 μL of 30% NaOH solution, seal and shake, heat at 80 °C for 1 h, centrifuge and take the supernatant for injection ;

Dicyclohexylamine sample recovery solution: Weigh 80 mg of favipiravir sample, add 1.0 ml of dicyclohexylamine control solution to dissolve; add 150 μL of 30% NaOH solution, seal and shake, heat at 80 °C for 1 h, and centrifuge to remove Clear liquid injection.

Group 6: Dicyclohexylamine control solution: prepare 1.6μg/ml dicyclohexylamine solution; take 1.0ml of this solution, add 150μL of 30% NaOH solution, seal and shake;

Sample solution: Weigh 80 mg of favipiravir sample, add 1.0 ml of N,N dimethylacetamide to dissolve; add 150 μL of 30% NaOH solution, seal and shake, heat at 80 °C overnight, and centrifuge to take the supernatant for injection ;

Dicyclohexylamine sample recovery solution: Weigh 80 mg of favipiravir sample, add 1.0 ml of dicyclohexylamine control solution to dissolve; add 150 μL of 30% NaOH solution, seal and shake, heat at 80 °C overnight, and centrifuge Clear liquid injection.

Group 7: Dicyclohexylamine control solution: prepare 1.6μg/ml dicyclohexylamine solution; take 1.0ml of this solution, add 150μL of 30% NaOH solution, seal and shake;

Sample solution: Weigh 80 mg of favipiravir sample, add 1.0 ml of N,N dimethylacetamide to dissolve; add 150 μL of 30% NaOH solution, seal and shake, heat at 60 °C for 1 h, centrifuge and take the supernatant for injection ;

Dicyclohexylamine sample recovery rate solution: Weigh 80 mg of favipiravir sample, add 1.0 ml of dicyclohexylamine control solution to dissolve; add 150 μL of 30% NaOH solution, seal and shake, heat at 60 °C for 1 h, and centrifuge to remove Clear liquid injection.

Group 8: Dicyclohexylamine control solution: prepare 1.6μg/ml dicyclohexylamine solution; take 1.0ml of this solution, add 150μL of 30% NaOH solution, seal and shake;

Sample solution: Weigh 80 mg of favipiravir sample, add 1.0 ml of N,N dimethylacetamide to dissolve; add 150 μL of 30% NaOH solution, seal and shake, heat at 100 °C for 30 min, and centrifuge to take the supernatant for injection ;

Dicyclohexylamine sample recovery rate solution: Weigh 80 mg of favipiravir sample, add 1.0 ml of dicyclohexylamine control solution to dissolve; add 150 μL of 30% NaOH solution with a mass percentage concentration of g/g, seal and shake, at 100 ° C Heating in medium for 30 min, centrifuging to take the supernatant for injection.

The above results are shown in Table 3:

table 3

Conclusion: Through the analysis of eight groups of comparative experiments, the optimized parameters of the volume of alkali solution added to the sample solution, the placing time and the placing temperature are: 150 μl of 30% sodium hydroxide solution, mix well, seal and shake, and place in an 80 ℃ oven for 1 hour; take out and place After room temperature, pipette the liquid into the direct injection bottle; centrifugal injection can eliminate the interference analysis of the sample matrix on dicyclohexylamine. This method has a good recovery rate.

Example 3

Chromatographic conditions: Agilent HP-5 gas chromatography column, stationary phase is (5%-phenyl)-methyl polysiloxane, size: 30m×0.53mm×5.00μm, flow rate is 4.0ml/min, split ratio is 1 : 1; programmed temperature rises to 40°C for 3min, 10°C/min to 200°C and hold for 5min; 20°C/min to 220°C for 10min;

Diluent: N,N dimethylacetamide;

30% sodium hydroxide solution: Weigh 30g of sodium hydroxide, add 70g of water to dissolve and mix.

Blank solution: Pipette 1.0 ml of diluent into the direct injection bottle, add 150 μl of 30% sodium hydroxide solution and mix well.

Dicyclohexylamine reference solution: take 16mg of dicyclohexylamine, accurately weighed, put it in a 100ml volumetric flask to dissolve with diluent and dilute to the mark, and mix well; accurately pipette 1.0ml into a 100ml volumetric flask, dilute with diluent to Scale, mix well; take 1.0ml into the direct injection bottle, add 150μl of 30% sodium hydroxide solution, mix well, and inject directly.

Sample solution: Weigh 80 mg of favipiravir sample, add 1.0 ml of diluent to dissolve, then add 150 μl of 30% sodium hydroxide solution to mix, seal and shake, and heat at 80 °C for 1 h; take out and cool to room temperature, and centrifuge to take the supernatant , pipette the supernatant into the injection bottle and inject directly; prepare 2 copies in parallel. After the system is equilibrated, inject blank solution; continuously inject 6 injections of dicyclohexylamine control solution, and then inject 1 injection of sample solution;

According to the dicyclohexylamine peak area in the chromatograms of the control solution and the sample solution, the content of dicyclohexylamine in the favipiravir sample was calculated according to the external standard method.

Results: Dicyclohexylamine was not detected in the favipiravir samples (<4ppm).

Claims (9)

1. A gas chromatographic detection method for dicyclohexylamine in favipiravir, characterized in that the detection sample in the gas chromatographic detection is pretreated by adding sodium hydroxide solution, and the sodium hydroxide solution is a mass percent concentration unit It is g/g 30% sodium hydroxide aqueous solution, and the pretreatment is heating at 80° C. for 1 h.
2. A gas chromatographic detection method for dicyclohexylamine in favipiravir according to claim 1, wherein the concentration of dicyclohexylamine in the detection sample in the detection sample is 4ppm-30ppm.
3. The gas chromatography detection method of dicyclohexylamine in a kind of favipiravir according to claim 1, is characterized in that, described gas chromatography detection method comprises the following steps:

   1) Preparation of standard samples: take dicyclohexylamine, add diluent N,N dimethylacetamide to dissolve, and configure it into a linear dicyclohexylamine reference solution with a linear concentration range; take the linear dicyclohexylamine reference solution respectively In the injection bottle, add 30% sodium hydroxide solution with a mass percentage concentration unit of g/g, mix well, seal and shake;

   2) Preparation of test samples: Weigh the favipiravir sample, add diluent N,N dimethylacetamide to dissolve, then add 30% sodium hydroxide solution to mix, seal and shake; heat at 80°C for 1 hour, take out and cool To room temperature, centrifuge to take the supernatant, transfer the supernatant to the injection bottle; wait for the injection to detect;

   3) Gas chromatographic detection: carry out gas chromatographic detection with the above-mentioned standard sample and the detection sample, take the concentration of the linear control solution as the abscissa and the peak area as the ordinate, and draw the standard curve of the linear equation; calculate the bicyclic ring in favipiravir by the external standard method Hexylamine content.
4. The gas chromatography detection method of dicyclohexylamine in favipiravir according to any one of claims 1-3, characterized in that the detection limit concentration of the dicyclohexylamine is: 0.096 μg/ml.
5. The gas chromatography detection method of dicyclohexylamine in a kind of favipiravir according to claim 3, is characterized in that, in described step (1), the concentration range of linear dicyclohexylamine control solution is: 0.32 μg/ml ~3.20 μg/ml; in the step (1), the volume ratio of the linear dicyclohexylamine control solution to 30% sodium hydroxide is 20:3.
6. The gas chromatographic detection method of dicyclohexylamine in a kind of favipiravir according to claim 3, it is characterized in that, in described step (2), the difference between favipiravir sample and N,N dimethylacetamide The weight-to-volume ratio is 80:1, in mg/ml; the volume ratio of the N,N dimethylacetamide to 30% sodium hydroxide is 20:3.
7. The gas chromatographic detection method of dicyclohexylamine in a kind of favipiravir according to claim 3, is characterized in that, the chromatographic column that the gas chromatographic detection in described step (3) is: Agilent HP-5 gas chromatograph Column, the stationary phase is (5%-phenyl)-methyl polysiloxane, size: 30m×0.53mm×5.00μm, and the carrier gas is nitrogen.
8. The gas chromatography detection method of dicyclohexylamine in a kind of favipiravir according to claim 3, is characterized in that, the condition of gas chromatography detection in described step (3) is: flow rate 3.5～4.5ml/min , the initial column temperature is 35°C to 45°C, and the split ratio is 0.8:1 to 1.2:1; programmed temperature rises: 40°C for 3min, 10°C/min to 200°C and hold for 5min; 20°C/min to 220°C for 5min 10min.
9. The gas chromatography detection method of dicyclohexylamine in a kind of favipiravir according to claim 8, is characterized in that, the condition of gas chromatography detection in described step (3) is: flow velocity is 4.0ml/min, The initial column temperature was 40°C and the split ratio was 1:1.

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