CN115541755B

CN115541755B - Quality control method of nifuratel tablet

Info

Publication number: CN115541755B
Application number: CN202211218858.6A
Authority: CN
Inventors: 陈妙秀; 蓝永锋; 李慧敏; 梁嘉琪; 吴儒超
Original assignee: GUANGDONG HENGJIAN PHARMACEUTICAL CO Ltd
Current assignee: GUANGDONG HENGJIAN PHARMACEUTICAL CO Ltd
Priority date: 2022-09-29
Filing date: 2022-09-29
Publication date: 2023-10-27
Anticipated expiration: 2042-09-29
Also published as: CN115541755A

Abstract

The invention belongs to the technical field of medicine quality control, and particularly relates to a quality control method of nifuratel tablets, which adopts high performance liquid chromatography, and the conditions are set as follows: octadecyl bonded silica gel chromatographic column, column temperature 30deg.C, sample injection amount 10μl, flow rate 1.0ml/min, detection wavelength 210nm, and eluting with organic phase-water phase as mobile phase. The high performance liquid chromatography provided by the invention has good repeatability, stability and instrument and chromatographic condition adaptability, the detection sensitivity and separation degree of six impurities or components such as oxidized impurity II, oxidized impurity III, impurity A, impurity B, impurity C and nifuratel in the nifuratel tablet are high, the signal to noise ratio (S/N) is more than 10.0, the RSD is less than 10%, the measurement result is ensured to have good stability, the detection durability of the nifuratel tablet can be obviously improved, and the method is simple, quick and sensitive, and the impurity level in the product can be effectively controlled.

Description

Quality control method of nifuratel tablet

Technical Field

The invention belongs to the technical field of medicine quality control, and particularly relates to a quality control method of nifuratel tablets.

Technical Field

Nifuratel is a broad-spectrum antibiotic, clinically used as a gynecological antibacterial drug for treating bacterial vaginitis. The structural formula is as follows:

the synthetic route of the nifuratel which is mature in industry at present is shown as follows:

intermediate IP01 is prepared from starting material SM01 (impurity C) under the condition of sulfuric acid, intermediate IP02 (impurity B) is prepared from starting material SM02 under the condition of dimethyl carbonate, and then intermediate IP01 and intermediate IP02 are condensed under the condition of sulfuric acid to prepare nifuratel. However, due to the oxidizing nature of sulfuric acid, the thioethers in nifuratel may be further oxidized to form oxidized impurities II and III. The structural formula is as follows:

in the preparation of nifuratel from starting materials, multi-step reactions are involved, and there is a risk of residual starting materials and intermediates in the final nifuratel product, and at the same time, there is a risk of increased levels of oxidized impurities during the preparation and storage of nifuratel tablets. The above impurity information is as follows:

the polarity difference of the impurities is large, at present, few reports are about a method for simultaneously detecting various impurities in a nifuratel drug, for example, chinese patent CN201910052941.2 discloses an impurity control method for nifuratel vaginal tablets, which detects nifuratel, 5-nitrofurfural diacetate, 5-nifuratel pyridazine, nifuratel oxidized impurities and photodegradation impurities contained in nifuratel vaginal tablets by high performance liquid chromatography, but the separation degree of the substances obtained by the method is low, cross coincidence exists between impurity peaks, and meanwhile, the specific structures of the oxidized and degraded impurities and photodegradation impurities are not definitely detected by the method, so that better quality control is difficult to obtain; sun Guoxiang et al, HPLC content determination of 4 intermediates in nifuratel preparation process, including 2- (methylthiomethyl) -oxirane, 3-methylthio-2-hydroxy-propylhydrazine, N-amino-5-methylthiomethyl-2-oxazolidinone, 5-nitrofurfural, but this document mainly aims to solve the problem of product purity control in nifuratel synthesis process, it is difficult to perform more comprehensive quality control on nifuratel drug storage process (Sun Guoxiang, deng Haiying, lifei. HPLC method to determine the content of 4 intermediates of nifuratel and related substances [ J ]. J.North-West pharmaceutical J, 2011,26 (005): 334-337); yinghua the preparation and quality control of nifuratel vaginal tablet are studied, and high performance liquid chromatography is adopted to detect nifuratel and 5-nitrofurfural diacetate in nifuratel vaginal tablet (Yinghua. Preparation and quality control of nifuratel vaginal tablet [ J ]. Chinese medical journal, 2016,8:852-853,857), but since nifuratel tablet can produce degradation, oxidation and the like in the preparation and storage process, the impurity content is more, the literature only detects single impurity in the preparation process, and the comprehensive quality control of nifuratel drug is difficult, therefore, a simple, rapid and sensitive detection method is developed, and a plurality of impurities in nifuratel drug are detected simultaneously, thus providing important basis for the quality control of nifuratel drug.

Disclosure of Invention

Aiming at the problems in the prior art, the invention provides a quality control method of nifuratel tablets, and the detection method has the advantages of simple and quick sample treatment, sensitivity, easy operation and good method adaptability, can effectively detect a plurality of impurities in nifuratel tablets at the same time, and has excellent separation and detection effects.

In a first aspect, the invention provides a quality control method of nifuratel tablets, wherein the quality control method is high performance liquid chromatography.

Further, the conditions of the high performance liquid chromatography adopted by the invention are as follows:

chromatographic column: adopting octadecyl bonded silica gel chromatographic column;

column temperature: 25-35 ℃;

flow rate: 0.8 ml/min-1.2 ml/min;

sample injection amount: 5-20 mu l;

detection wavelength: 205nm to 215nm;

mobile phase: mixing organic phase and water phase;

the mobile phase programming is shown in table 1:

table 1: mobile phase procedure

Time (min)	Aqueous phase (%)	Organic phase (%)
			0	90～70	10～30
2	90～70	10～30
			13	50～30	50～70
13.1	90～70	10～30
			20	90～70	10～30

In a second aspect, the invention provides specific steps of a quality control method of the nifuratel tablet:

s1, preparing a blank solution: acetonitrile and water are mixed according to the volume ratio of 40:60, uniformly mixing to prepare a blank solution;

s2, reference substance stock solution: precisely weighing oxidized impurity II, oxidized impurity III, impurity A, impurity B, impurity C and nifuratel reference substances, respectively placing into a measuring flask, dissolving and diluting with acetonitrile to scale, and shaking uniformly to obtain oxidized impurity II, oxidized impurity III, impurity A, impurity B, impurity C and nifuratel reference substance stock solution;

s3, reference substance solution: precisely measuring oxidized impurities II, oxidized impurities III, impurities A, impurities B, impurities C and nifuratel reference substance stock solution in the step S2, placing the stock solution in the same measuring flask, diluting to scale with blank solution, shaking uniformly to obtain reference substance solution, and sampling under the set high performance liquid chromatography condition to complete analysis;

s4, sample solution: grinding nifuratel tablet into powder, placing into a measuring flask, adding a small amount of acetonitrile, performing ultrasonic dissolution, diluting with acetonitrile to scale, filtering, placing the filtrate into the measuring flask, diluting with blank solution to scale, shaking to obtain sample solution, and performing sample injection under the set high performance liquid chromatography condition to complete analysis.

Preparing a positioning solution, a sensitivity solution and a separation degree solution according to the experimental conditions and the method respectively:

(1) Positioning solution: respectively measuring the reference stock solutions of the oxidized impurities II, the oxidized impurities III, the impurities A, the impurities B and the impurities C in the step S2, respectively placing the reference stock solutions in a measuring flask, diluting the reference stock solutions to scale with acetonitrile, and shaking the reference stock solutions uniformly to obtain positioning solutions of the oxidized impurities II, the oxidized impurities III, the impurities A, the impurities B and the impurities C;

(2) Sensitivity solution: precisely measuring the reference substance solution in the step S3, placing the reference substance solution in a measuring flask, diluting the reference substance solution to a scale with a blank solution, and shaking the solution uniformly to obtain a sensitivity solution;

(3) Degree of separation solution: and (3) placing nifuratel powder in the step (S4) in a measuring flask, adding a small amount of acetonitrile, carrying out ultrasonic dissolution, diluting to a scale with acetonitrile, filtering, placing the subsequent filtrate in the measuring flask, precisely measuring the reference substance positioning solutions of oxidized impurities II, oxidized impurities III, impurities A, impurities B and impurities C, placing the reference substance positioning solutions in the 10ml measuring flask, fully mixing, diluting to the scale with a blank solution, and shaking uniformly to obtain a separation degree solution (100% of the solution for adding the standard sample).

The molecular structural formulas of the oxidized impurities II, III, A, B and C are as follows:

oxidizing impurity II:

oxidizing impurity III:

impurity A: 5-Nifuropyridazine (Process impurity in preparation)

Impurity B: 2-amino-5-methylthiomethyl-2-oxazolidinone (intermediate in the preparation process)

Impurity C: 5-Nitrofurfural diacetate (starting Material impurity during preparation)

The quality control method of the nifuratel tablet provided by the invention is not limited to the quality control of the nifuratel tablet, and can also comprise other dosage forms, such as capsules, pills and the like.

Compared with the prior art, the invention has the following beneficial effects:

the high performance liquid chromatography provided by the invention has good repeatability, good stability of the solution of the test sample, good adaptability of instruments and chromatographic conditions, high detection sensitivity and separation degree of six impurities or components such as oxidized impurity II, oxidized impurity III, impurity A, impurity B, impurity C, nifuratel and the like in the nifuratel tablet, and a signal to noise ratio (S/N) of more than 10.0, RSD of less than 10%, good stability of a measurement result, and capability of greatly improving the detection durability of the nifuratel tablet, and the quality control method of the nifuratel tablet is successfully developed.

Drawings

FIG. 1 is a chromatogram of a hollow white solution of example 1.

FIG. 2 is a chromatogram of the control solution in example 1.

FIG. 3 is a chromatogram of the sensitivity solution in example 1.

FIG. 4 is a chromatogram of the sample solution in example 1.

FIG. 5 is a chromatogram of the resolution solution of example 1.

FIG. 6 is a chromatogram of the resolution solution of example 2.

FIG. 7 is a chromatogram of the resolution solution of example 3.

FIG. 8 is a chromatogram of the resolution solution of example 6.

FIG. 9 is a chromatogram of the resolution solution of example 7.

FIG. 10 is a chromatogram of the resolution solution of example 8.

FIG. 11 is a chromatogram of the resolution solution of example 9.

FIG. 12 is a chromatogram of the resolution solution of example 10.

FIG. 13 is a chromatogram of the resolution solution of example 11.

FIG. 14 is a chromatogram of the resolution solution of example 12.

FIG. 15 is a chromatogram of the resolution solution of example 13.

Detailed Description

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. The terminology used in the description of the invention herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention.

The present invention will be further described in detail with reference to the following embodiments, in order to make the objects, technical solutions and advantages of the present invention more apparent. It should be understood that the description is only illustrative and is not intended to limit the scope of the invention. In addition, in the following description, descriptions of well-known structures and techniques are omitted so as not to unnecessarily obscure the present invention.

All other embodiments obtained by persons of ordinary skill in the art without making any creative effort based on the embodiments of the present invention are within the protection scope of the present invention, and the following embodiments are further described for the present invention, but are not meant to limit the protection scope of the present invention.

The specific sources and types of partial raw materials and instruments used in the invention are shown in table 1:

example 1

The chromatographic conditions set in the high performance liquid chromatography method are as follows:

instrument: thermo U3000 high performance liquid chromatograph;

chromatographic column: octadecyl bonded silica gel column (specification: 150 x 4.6mm,5 um);

column temperature: 30 ℃;

sample injection amount: 10 μl;

flow rate: 1.0ml/min;

detection wavelength: 210nm;

mobile phase: the organic phase is acetonitrile, the aqueous phase is ultrapure water, and the specific table 2 shows;

table 2:

time (min)	Ultrapure water (%)	Acetonitrile (%)
			0	80	20
2	80	20
			13	40	60
13.1	80	20
			20	80	20

The specific experimental steps are as follows:

s1, blank solution: acetonitrile-water (volume ratio 40:60);

s2, reference substance stock solution: precisely weighing 20mg of oxidized impurity II, oxidized impurity III, impurity A, impurity B, impurity C and nifuratel reference substance respectively, putting into 100ml measuring flask, respectively, dissolving and diluting with acetonitrile to scale, shaking uniformly to obtain oxidized impurity II, oxidized impurity III, impurity A, impurity B, impurity C and nifuratel reference substance stock solution with concentration of 200 mug/ml;

s3, reference substance solution: precisely measuring 1.0ml of each of the oxidized impurity II, oxidized impurity III, impurity A, impurity B, impurity C and nifuratel reference substance stock solution in the step S2, placing the stock solutions in a same 100ml measuring flask, diluting to a scale with a blank solution, and shaking uniformly to obtain a reference substance solution with the concentration of 2 mug/ml;

s4, sample solution: taking 20 nifuratel tablets (200 mg in specification), grinding into powder, weighing 1000mg of powder (400 mg containing nifuratel), placing into a 100ml measuring flask, adding a small amount of acetonitrile, carrying out ultrasonic treatment to dissolve, and diluting with acetonitrile to a scale. Filtering, collecting 2.5ml of the filtrate, placing in a 10ml measuring flask, diluting to scale with blank solution, and shaking to obtain sample solution with concentration of 1 mg/ml.

Preparing blank solution, positioning solution, sensitivity solution and separation degree solution according to the experimental conditions and methods:

(1) Positioning solution: respectively measuring 1.0ml of each of the reference stock solutions of the oxidized impurities II, the oxidized impurities III, the impurities A, the impurities B and the impurities C in the step S2, respectively placing in a 10ml measuring flask, diluting to a scale with acetonitrile, and shaking uniformly to obtain positioning solutions of the oxidized impurities II, the oxidized impurities III, the impurities A, the impurities B and the impurities C with the concentration of 20 mug/ml respectively;

(2) Sensitivity solution: precisely measuring 2.5ml of the reference substance solution in the step S3, placing in a 10ml measuring flask, diluting to a scale with a blank solution, and shaking uniformly to obtain a sensitivity solution with the concentration of 0.5 mug/ml;

(3) Degree of separation solution: taking about 1000mg (about 400mg containing nifuratel) of the powder in the step S4, placing the powder in a 100ml measuring flask, adding a small amount of acetonitrile, carrying out ultrasonic treatment to dissolve, diluting with acetonitrile to a scale, filtering, taking 2.5ml of the subsequent filtrate, placing the filtrate in a 10ml measuring flask, precisely measuring 1ml of each of oxidized impurity II, oxidized impurity III, impurity A, impurity B and impurity C reference substance positioning solutions, placing the obtained solution in the 10ml measuring flask, mixing, diluting with a blank solution to the scale, shaking uniformly, and taking the obtained solution as a separation degree solution (100% of the standard sample solution).

The prepared blank solution, reference solution, sample solution, sensitivity solution and separation degree solution were subjected to high performance liquid chromatography under the above chromatographic conditions, and chromatograms were recorded, and the results are shown in fig. 1 (blank solution), fig. 2 (reference solution), fig. 3 (sensitivity solution), fig. 4 (sample solution) and fig. 5 (separation degree solution), and the minimum separation degree of the separation degree solution obtained by using the high performance liquid chromatography conditions of this example 1 was 4.02, and the minimum signal to noise ratio of the sensitivity solution was 58.0.

Example 2

instrument: thermo U3000 high performance liquid chromatograph;

chromatographic column: octadecyl bonded silica gel chromatographic column (150 x 4.6mm,5 um)

Column temperature: 30 DEG C

Sample injection amount: 10 μl of

Flow rate: 1.0ml/min

Detection wavelength: 210nm of

Mobile phase: the organic phase is acetonitrile, the aqueous phase is ultrapure water, and the specific table 3 shows;

table 3:

time (min)	Ultrapure water (%)	Acetonitrile (%)
			0	70	30
2	70	30
			13	30	70
13.1	70	30
			20	70	30

The specific experimental procedure is the same as in example 1, the blank solution and the separation degree solution are respectively taken, high performance liquid chromatography analysis is carried out under the chromatographic conditions, the chromatogram is recorded, the separation degree solution result is shown in fig. 6, the minimum separation degree in fig. 6 is 2.49, and the separation degree meets the requirement.

Example 3

instrument: thermo U3000 high performance liquid chromatograph;

column temperature: 30 ℃;

sample injection amount: 10 μl;

flow rate: 1.0ml/min;

detection wavelength: 210nm;

mobile phase: the organic phase is acetonitrile, the aqueous phase is ultrapure water, and the specific table 4 shows;

table 4:

time (min)	Ultrapure water (%)	Acetonitrile (%)
			0	90	10
2	90	10
			13	50	50
13.1	90	10
			20	90	10

The experimental procedure is the same as in example 1, the blank solution and the separation degree solution are respectively taken, high performance liquid chromatography analysis is carried out under the chromatographic conditions, the chromatogram is recorded, the separation degree solution result is shown in fig. 7, the minimum separation degree in fig. 7 is 3.72, and the separation degree meets the requirement.

Examples 1 to 3 are optimized processes of elution systems in the high performance liquid chromatography method, separation can be achieved by 3 elution systems, the retention time of each impurity is greatly influenced by different elution systems, the influence of the baseline on the impurities in example 1 is smaller than that in examples 2 and 3, and finally the high performance liquid chromatography method in example 1 is preferred.

Example 4

The chromatographic conditions set in the high performance liquid chromatography method were the same as in example 1;

the experimental steps are as follows:

the preparation methods of the blank solution, the reference solution, the test sample solution and the separation degree solution (100% of the labeled test sample solution) are the same as those of example 1, wherein 6 parts of the separation degree solution (100% of the labeled test sample solution) are prepared in parallel to be used as 1-6 parts of the 100% of the labeled solution.

Taking blank solution, reference solution, test solution and 100% standard test solution 1-6 respectively, performing high performance liquid chromatography under the above chromatographic conditions, recording the chromatogram, and the results are shown in Table 5 below;

table 5: yield results of addition of the mark

As shown in Table 5, the recovery rate of the 100% standard solution of 6 parts was 93.6% -106.2%, the recovery rate was 90% -108%, and the RSD (n=6) was 1.6% -4.2% < 10.0%, which meets the requirements.

Example 5

the experimental steps are as follows:

the preparation method of the blank solution and the sensitivity solution is the same as that of example 1, and high performance liquid chromatography analysis is carried out under the chromatography condition, wherein the sensitivity solution is injected in parallel for 6 times, and the result is shown in the following table 6;

table 6: sensitivity results

As shown in Table 6, the peak area RSD (n=6) of the sensitive solution is 0.5% -3.8% < 10.0%, and the signal to noise ratio (S/N) is 58.0-176.5 >10.0, which indicates that the high performance liquid chromatography p-nifuratel tablet has good detection precision and sensitivity for each impurity.

Example 6

The column temperature was set to 25 ℃ in the chromatographic conditions set in the high performance liquid chromatography method, and other chromatographic conditions were the same as in example 1;

the experimental steps are as follows:

the preparation method of the sensitivity solution and the separation degree solution is the same as that of example 1, high performance liquid chromatography analysis is carried out under the chromatographic conditions, and a chromatogram is recorded, and the result is shown in fig. 8;

as can be seen from the chromatogram in fig. 8, the minimum separation of the separation solution obtained by setting the column temperature to 25 ℃ in this example was 4.08, and the minimum signal-to-noise ratio of the sensitivity solution was 34.9, compared with the column temperature set to 30 ℃ (example 1).

Example 7

The column temperature was set to 35 ℃ in the chromatographic conditions set in the high performance liquid chromatography method, and other chromatographic conditions were the same as in example 1;

the experimental steps are as follows:

the preparation method of the sensitivity solution and the separation degree solution is the same as that of example 1, high performance liquid chromatography analysis is carried out under the chromatographic conditions, and a chromatogram is recorded, and the result is shown in fig. 9;

as can be seen from the results of fig. 9, the minimum separation of the separation solution obtained by setting the column temperature to 35 c in this example was 3.93 and the minimum signal-to-noise ratio of the sensitivity solution was 44.6, compared to the column temperature set to 30 c (example 1).

Example 8

The flow rate was set to 0.8ml/min in the chromatographic conditions set in the high performance liquid chromatography method, and the other chromatographic conditions were the same as in example 1;

the experimental steps are as follows:

the preparation method of the sensitivity solution and the separation degree solution is the same as that of example 1, high performance liquid chromatography analysis is carried out under the chromatographic conditions, and a chromatogram is recorded, and the result is shown in fig. 10;

as can be seen from the results of FIG. 10, the minimum separation of the separation solution obtained by setting the flow rate to 0.8ml/min in this example was 4.01 and the minimum signal-to-noise ratio of the sensitivity solution was 38.7, compared to the case where the flow rate was set to 1.0ml/min (example 1).

Example 9

The flow rate was set to 1.2ml/min in the chromatographic conditions set in the high performance liquid chromatography method, and the other chromatographic conditions were the same as in example 1;

the experimental steps are as follows:

the preparation method of the sensitivity solution and the resolution solution is the same as that of example 1, high performance liquid chromatography analysis is carried out under the chromatographic conditions, and a chromatogram is recorded, and the result is shown in fig. 11;

as can be seen from the results of FIG. 11, the minimum separation of the separation solution obtained by setting the flow rate to 1.2ml/min in this example was 4.00 and the minimum signal-to-noise ratio of the sensitivity solution was 36.4, compared to the case where the flow rate was set to 1.0ml/min (example 1).

Example 10

The sample injection amount was set to 5. Mu.l in the chromatographic conditions set in the high performance liquid chromatography method, and the other chromatographic conditions were the same as in example 1;

the experimental steps are as follows:

the preparation method of the sensitivity solution and the separation degree solution is the same as that of example 1, high performance liquid chromatography analysis is carried out under the chromatographic conditions, and a chromatogram is recorded, and the result is shown in fig. 12;

as can be seen from the results of FIG. 12, the minimum separation of the separation solution obtained by setting the sample amount to 5. Mu.l in this example was 6.91 and the minimum signal to noise ratio of the sensitivity solution was 15.4, compared with the sample amount set to 10. Mu.l (example 1).

Example 11

The sample injection amount was set to 20. Mu.l in the chromatographic conditions set in the high performance liquid chromatography method, and the other chromatographic conditions were the same as in example 1;

the experimental steps are as follows:

the preparation method of the sensitivity solution and the separation degree solution is the same as that of example 1, high performance liquid chromatography analysis is carried out under the chromatographic conditions, and a chromatogram is recorded, and the result is shown in fig. 13;

as can be seen from the results of FIG. 13, the minimum separation of the separation solution obtained by setting the sample amount to 20. Mu.l in this example was 3.18 and the minimum signal to noise ratio of the sensitivity solution was 54.3, compared to the sample amount set to 10. Mu.l (example 1).

Example 12

The detection wavelength was set to 205nm in the chromatographic conditions set in the high performance liquid chromatography method, and the other chromatographic conditions were the same as in example 1;

the experimental steps are as follows:

the preparation method of the sensitivity solution and the separation degree solution is the same as that of example 1, high performance liquid chromatography analysis is carried out under the chromatographic conditions, and a chromatogram is recorded, and the result is shown in fig. 14;

as can be seen from the results of fig. 14, the minimum separation of the separation solution obtained by setting the detection wavelength to 205nm in this example was 4.08, and the minimum signal-to-noise ratio of the sensitivity solution was 42.0, compared to the case where the wavelength was set to 210nm (example 1).

Example 13

The detection wavelength was set to 215nm in the chromatographic conditions set in the high performance liquid chromatography method, and the other chromatographic conditions were the same as in example 1;

the experimental steps are as follows:

the preparation method of the sensitivity solution and the resolution solution is the same as that of example 1, high performance liquid chromatography analysis is carried out under the chromatographic conditions, and a chromatogram is recorded, and the result is shown in fig. 15;

as can be seen from the results of fig. 15, the minimum separation of the separation solution obtained by setting the detection wavelength to 215nm in this example was 4.09, and the minimum signal-to-noise ratio of the sensitivity solution was 35.5, compared to the detection wavelength set to 210nm (example 1).

Examples 6 to 13 are the investigation of chromatographic conditions in different durability ranges, the system applicability can meet the requirements, and the results of the examples are summarized in Table 7;

table 7: summary of results from different chromatographic conditions

It is apparent that the above examples are given by way of illustration only and are not limiting of the embodiments. Other variations or modifications of the above teachings will be apparent to those of ordinary skill in the art. It is not necessary here nor is it exhaustive of all embodiments. While still being apparent from variations or modifications that may be made by those skilled in the art are within the scope of the invention.

Claims

1. The quality control method of nifuratel tablet is characterized in that the quality control method is high performance liquid chromatography, and the mobile phase program of the liquid chromatography is set as follows:

0min: 80-90% of water phase and 10-20% of organic phase;

2min: 80-90% of water phase and 10-20% of organic phase;

13min: 40-50% of water phase and 50-60% of organic phase;

13.1min: 80-90% of water phase and 10-20% of organic phase;

20min: 80-90% of water phase and 10-20% of organic phase;

the organic phase is acetonitrile;

the high performance liquid chromatography adopts octadecyl bonded silica gel chromatographic column;

the quality control process is that high performance liquid chromatography detects nifuratel and five impurity components therein simultaneously, the five impurity components include: the impurity A is 5-nifuradazine, the impurity B is 2-amino-5-methylthiomethyl-2-oxazolidone, and the impurity C is 5-nitrofurfural diacetate, oxidized impurity II and oxidized impurity III;

the structural formula of the oxidized impurity II is；

The structural formula of the oxidized impurity III is。

2. The quality control method of nifuratel tablet according to claim 1, characterized in that the column temperature of said high performance liquid chromatography is 25-35 ℃.

3. The quality control method of nifuratel tablet according to claim 1, characterized in that the flow rate of said high performance liquid chromatography is 0.8ml/min to 1.2ml/min.

4. The quality control method of nifuratel tablet according to claim 1, characterized in that the sample injection amount of the high performance liquid chromatography is 5-20 μl.

5. The quality control method of nifuratel tablet according to claim 1, characterized in that the detection wavelength of said high performance liquid chromatography is 205 nm-215 nm.

6. The quality control method of nifuratel tablet according to any one of claims 1 to 5, characterized by comprising the steps of:

s3, reference substance solution: precisely measuring oxidized impurity II, oxidized impurity III, impurity A, impurity B, impurity C and nifuratel reference substance stock solution in the step S2, placing the stock solution in the same measuring flask, diluting to scale with blank solution, shaking uniformly to obtain reference substance solution, and injecting under the set high performance liquid chromatography condition;

7. The method for quality control of nifuratel tablet according to claim 1, characterized in that said mobile phase procedure of liquid chromatography is set as:

0min: 80% of ultrapure water and 20% of acetonitrile;

2min: 80% of ultrapure water and 20% of acetonitrile;

13min: ultrapure water 40%, acetonitrile 60%;

13.1min: 80% of ultrapure water and 20% of acetonitrile;

20min: the ultrapure water was 80% and the acetonitrile was 20%.