CN115541755A

CN115541755A - Quality control method of nifuratel tablets

Info

Publication number: CN115541755A
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: 2022-12-30
Anticipated expiration: 2042-09-29
Also published as: CN115541755B

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 as follows: octadecyl bonded silica gel chromatographic column, column temperature of 30 deg.C, sample amount of 10 μ l, flow rate of 1.0ml/min, detection wavelength of 210nm, and eluting with organic phase-water phase as mobile phase. The high performance liquid chromatography has good repeatability, stability, adaptability of instruments and chromatographic conditions, high detection sensitivity and separation degree of six impurities or components such as oxidized impurities II, oxidized impurities III, impurities A, impurities B, impurities C, nifuratel and the like in the nifuratel tablet, signal to noise ratio (S/N) >10.0, RSD & ltn & gt 10%, good stability of a determination result is ensured, the detection durability of the nifuratel tablet can be obviously improved, and the method is simple, quick and sensitive, and can effectively control the impurity level in a product.

Description

Quality control method of nifuratel tablets

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, and is clinically used as a gynecological antibacterial drug for treating bacterial vaginitis. The structural formula is as follows:

the current industrially mature synthetic route of nifuratel is as follows:

preparing an intermediate IP01 from a starting material SM01 (impurity C) under the condition of sulfuric acid, preparing an intermediate IP02 (impurity B) from a starting material SM02 under the condition of dimethyl carbonate, and then condensing the intermediate IP01 and the intermediate IP02 under the condition of sulfuric acid to prepare the nifuratel. However, due to the oxidative properties of sulfuric acid, the thioether in nifuratel may be further oxidized to form oxidized impurity II and oxidized impurity III. The structural formula is as follows:

in the process of preparing nifuratel from starting materials, multi-step reactions are involved, each starting material and intermediate in the nifuratel finished product have the risk of residue, and meanwhile, during the preparation and storage of nifuratel tablets, the risk of increasing the content of oxidized impurities also exists. The information of the impurities is shown in the following table:

the polarity of the impurities is relatively large, and at present, reports of methods for simultaneously detecting related substances by using various impurities in nifuratel medicaments are few, for example, chinese patent CN201910052941.2 discloses an impurity control method for nifuratel vaginal tablets, the method detects nifuratel, 5-nitrofurfural diacetate, 5-nifuratel, nifuratel oxidized impurities and photodegradable impurities contained in nifuratel vaginal tablets by using a high performance liquid chromatography, but the separation degree of substances obtained by the method is low, the cross coincidence exists among impurity peaks, the specific structures of the oxidized and degraded impurities and the photodegradable impurities are not clear, and the better quality control is difficult to obtain; HPLC content measurement is carried out on 4 intermediates in the preparation process of nifuratel by Sun Guxiang et al, wherein the HPLC content measurement comprises 2- (methylthiomethyl) -oxetane, 3-methylthio-2-hydroxy-propylhydrazine, N-amino-5-methylthiomethyl-2-oxazolidinone and 5-nitrofurfural, but the document mainly aims to solve the problem of product purity control in the synthetic process of nifuratel and is difficult to carry out comprehensive quality control on the storage process of nifuratel medicines (Sun Gu, deng Haiying, li Yan Fei. HPLC method is used for measuring the content of 4 intermediates of nifuratel and related substances [ J ]. Northwest pharmaceutical journal, 2011,26 (005): 334-337); a research on the preparation and quality control of nifuratel vaginal tablets is carried out by Yinghua, which adopts high performance liquid chromatography to detect nifuratel and 5-nitrofurfural diacetate in nifuratel vaginal tablets (preparation and quality control of nifuratel vaginal tablets [ J ]. 2016,8, 852-853, 857), but because nifuratel tablets have more impurities caused by degradation, oxidation and the like in the preparation and storage processes, the document only detects one impurity in the preparation process, and is difficult to carry out comprehensive quality control on nifuratel medicaments, so that a simple, quick and sensitive detection method is developed, a plurality of impurities in nifuratel medicaments are simultaneously detected, and an important basis is provided for the quality control of nifuratel medicaments.

Disclosure of Invention

Aiming at the problems in the prior art, the invention provides a quality control method of nifuratel tablets.

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

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

a chromatographic column: octadecyl bonded silica gel chromatographic column is adopted;

column temperature: 25-35 ℃;

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

sample introduction amount: 5-20 mul;

detection wavelength: 205 nm-215 nm;

mobile phase: mixing organic phase and water phase;

the mobile phase program settings are 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 the specific steps of the quality control method of nifuratel tablets:

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

s2, comparison product stock solution: precisely weighing an oxidized impurity II, an oxidized impurity III, an impurity A, an impurity B, an impurity C and a nifuratel reference substance, respectively placing the oxidized impurity II, the oxidized impurity III, the impurity A, the impurity B, the impurity C and the nifuratel reference substance into a measuring flask, dissolving and diluting the substances to a scale by using acetonitrile, and shaking the substances uniformly to obtain a reference substance storage solution of the oxidized impurity II, the oxidized impurity III, the impurity A, the impurity B, the impurity C and the nifuratel;

s3, comparison product 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 reference substance stock solution into the same measuring flask, diluting the reference substance stock solution to a scale by using a blank solution, shaking the reference substance stock solution uniformly to obtain a reference substance solution, and injecting the sample under the set high performance liquid chromatography condition to finish analysis;

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

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

(1) Positioning solution: respectively measuring reference substance stock solutions of oxidized impurities II, oxidized impurities III, impurities A, impurities B and impurities C in the step S2, respectively placing the reference substance stock solutions into measuring flasks, diluting the reference substance stock solutions to a scale with acetonitrile, and shaking the reference substance stock solutions uniformly to respectively 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 obtained in the step S3, placing the reference substance solution into a measuring flask, diluting the reference substance solution to a scale with a blank solution, and shaking up to obtain a sensitivity solution;

(3) Resolution solution: and (5) putting the nifuratel powder obtained in the step (S4) into a measuring flask, adding a small amount of acetonitrile for ultrasonic dissolution, diluting the powder to a scale with the acetonitrile, filtering, putting a subsequent filtrate into the measuring flask, precisely measuring reference substance positioning solutions of the oxidized impurities II, the oxidized impurities III, the impurities A, the impurities B and the impurities C, putting the reference substance positioning solutions into the 10ml measuring flask for full mixing, diluting the solution to the scale with a blank solution, shaking up, and taking the solution as a resolution solution (100% of the added sample solution).

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

oxidizing impurities II:

oxidizing impurities III:

impurity A: 5-nifuropyridazine (technical impurities in the preparation process)

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

Impurity C: 5-Nitrofural diacetic acid ester (starting material impurity in preparation process)

The quality control method of the nifuratel tablets provided by the invention is not limited to the quality control of the nifuratel tablets, 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 the advantages of good repeatability, good stability of a test solution, good adaptability of instruments and chromatographic conditions, high detection sensitivity and separation degree for six impurities or components such as oxidized impurities II, oxidized impurities III, impurities A, impurities B, impurities C, nifuratel and the like in the nifuratel tablet, signal to noise ratio (S/N) >10.0, RSD more than 10%, good stability of a determination result is ensured, detection durability of the nifuratel tablet can be greatly improved, and a quality control method of the nifuratel tablet is successfully developed.

Drawings

FIG. 1 is an air white solution chromatogram in example 1.

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

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

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

Fig. 5 is a resolution solution chromatogram in example 1.

Fig. 6 is a resolution solution chromatogram in example 2.

Fig. 7 is a resolution solution chromatogram in example 3.

Fig. 8 is a resolution solution chromatogram in example 6.

Fig. 9 is a resolution solution chromatogram in example 7.

FIG. 10 is a resolution solution chromatogram in example 8.

FIG. 11 is a resolution solution chromatogram in example 9.

FIG. 12 is a resolution solution chromatogram in example 10.

FIG. 13 is a resolution solution chromatogram in example 11.

Fig. 14 is a resolution solution chromatogram in example 12.

FIG. 15 is a resolution solution chromatogram in 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.

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

All other embodiments obtained by a person skilled in the art without making any inventive step based on the embodiments of the present invention are within the scope of the present invention, and the following embodiments further describe the present invention, but the present invention is not limited to the embodiments.

The specific sources and models of part of raw materials and instruments and equipment used by the invention are shown in Table 1:

example 1

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

the instrument comprises the following steps: thermo U3000 high performance liquid chromatograph;

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

column temperature: 30 ℃;

sample injection amount: 10 mu l of the mixture;

flow rate: 1.0ml/min;

detection wavelength: 210nm;

mobile phase: the organic phase is acetonitrile, and the water phase is ultrapure water, which is shown in table 2 specifically;

table 2:

time (min)	Ultra pure 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;

s2, reference substance storage solution: precisely weighing 20mg of each of the oxidized impurity II, the oxidized impurity III, the impurity A, the impurity B, the impurity C and the nifuratel reference substance, respectively placing the weighed substances into a 100ml measuring flask, dissolving and diluting the weighed substances to a scale by using acetonitrile, and shaking the weighed substances uniformly to obtain oxidized impurity II, oxidized impurity III, impurity A, impurity B, impurity C and nifuratel reference substance storage solutions with the concentration of 200 mu g/ml;

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

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

Preparing blank solution, positioning solution, sensitivity solution and resolution solution according to the experimental conditions and the method respectively:

(1) Positioning solution: respectively measuring 1.0ml of reference substance 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 substance stock solutions in 10ml measuring bottles, diluting the reference substance stock solutions to a scale with acetonitrile, shaking up, and respectively obtaining 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 mu g/ml;

(2) Sensitivity solution: precisely measuring 2.5ml of the reference substance solution obtained in the step S3, putting the reference substance solution into a 10ml measuring flask, diluting the reference substance solution to a scale with a blank solution, and shaking up to obtain a sensitivity solution with the concentration of 0.5 mu g/ml;

(3) Resolution solution: taking about 1000mg of the powder (about 400mg of nifuratel) obtained in the step S4, placing the powder in a 100ml measuring flask, adding a small amount of acetonitrile for ultrasonic dissolution, diluting the powder to a scale with the acetonitrile, filtering, taking 2.5ml of subsequent filtrate, placing the subsequent filtrate in a 10ml measuring flask, precisely measuring 1ml of 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 for mixing, diluting the reference substance positioning solutions to a scale with a blank solution, shaking up, and taking the mixed solution as a resolution solution (100% added with a standard sample solution).

The prepared blank solution, reference solution, test solution, sensitivity solution and resolution solution were subjected to high performance liquid chromatography analysis 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 (test solution) and fig. 5 (resolution solution), and the minimum resolution of the resolution solution obtained by using the high performance liquid chromatography conditions of example 1 was 4.02, and the minimum signal-to-noise ratio of the sensitivity solution was 58.0.

Example 2

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

Column temperature: 30 deg.C

Sample injection amount: 10 μ l

Flow rate: 1.0ml/min

Detection wavelength: 210nm

Mobile phase: the organic phase is acetonitrile, and the water phase is ultrapure water, which is shown in table 3 specifically;

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 steps are the same as example 1, the blank solution and the resolution solution are respectively taken, high performance liquid chromatography analysis is carried out under the chromatographic conditions, a chromatogram is recorded, the resolution solution result is shown in figure 6, the minimum resolution in figure 6 is 2.49, and the resolution meets the requirements.

Example 3

column temperature: 30 ℃;

sample introduction amount: 10 mu l of the mixture;

flow rate: 1.0ml/min;

detection wavelength: 210nm;

mobile phase: the organic phase is acetonitrile, and the water phase is ultrapure water, which is shown in table 4 specifically;

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 that in example 1, the blank solution and the resolution solution are respectively taken, high performance liquid chromatography analysis is carried out under the chromatographic conditions, the chromatogram is recorded, the resolution solution result is shown in figure 7, the minimum resolution in figure 7 is 3.72, and the resolution meets the requirement.

Examples 1 to 3 are optimization processes of elution systems in the high performance liquid chromatography method, 3 elution systems can realize separation, different elution systems have large influence on retention time of each impurity, and in example 1, compared with examples 2 and 3, impurities are less influenced by a base line, and the high performance liquid chromatography method in example 1 is finally preferred.

Example 4

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

the experimental procedure is as follows:

blank solution, reference solution, sample solution, and separation degree solution (100% spiked sample solution) were prepared in the same manner as in example 1, wherein 6 parts of separation degree solution (100% spiked sample solution) were prepared in parallel as 100% spiked solutions 1 to 6.

Taking a blank solution, a reference solution, a test solution and 100% of standard test solution 1-6 respectively, carrying out high performance liquid chromatography analysis under the chromatographic conditions, and recording a chromatogram map, wherein the result is shown in a following table 5;

table 5: result of recovery rate of standard addition

The results in Table 5 show that the recovery rates of 6 parts of the 100% standard solution were 93.6% to 106.2%, both of which were in the range of 90% to 108%, and RSD (n = 6) was 1.6% to 4.2% < 10.0%, which met the requirements.

Example 5

the experimental procedure is as follows:

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

table 6: results of sensitivity

The results in Table 6 show that the detection precision and sensitivity of the high performance liquid chromatography of the invention to each impurity in nifuratel tablets are good, as shown by the results, the peak area RSD (N = 6) of the sensitivity solution is 0.5% -3.8% < 10.0%, and the signal-to-noise ratio (S/N) is 58.0-176.5 > 10.0.

Example 6

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

the experimental procedure is as follows:

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

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

Example 7

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

the experimental procedure is as follows:

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

from the results of fig. 9, it can be seen that the minimum resolution of the resolution solution obtained in this example with the column temperature set at 35 ℃ was 3.93 and the minimum signal-to-noise ratio of the sensitivity solution was 44.6, compared to the column temperature set at 30 ℃ (example 1).

Example 8

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

the experimental procedure is as follows:

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

from the results of FIG. 10, it can be seen that the minimum resolution of the resolution solution obtained in this example with the flow rate set at 0.8ml/min was 4.01 and the minimum signal-to-noise ratio of the sensitivity solution was 38.7, compared to the flow rate set at 1.0ml/min (example 1).

Example 9

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

the experimental procedure is as follows:

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

from the results of FIG. 11, it can be seen that the minimum resolution of the resolution solution obtained in this example is 4.00 and the minimum signal-to-noise ratio of the sensitivity solution is 36.4 when the flow rate is set to 1.2ml/min, compared to the flow rate set to 1.0ml/min (example 1).

Example 10

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

the experimental procedure is as follows:

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

from the results of fig. 12, it can be seen that the minimum resolution of the resolution solution obtained in this example with the sample volume set to 5 μ l is 6.91 and the minimum signal-to-noise ratio of the sensitivity solution is 15.4, compared to the sample volume set to 10 μ l (example 1).

Example 11

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

the experimental procedure is as follows:

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

from the results of fig. 13, it can be seen that the minimum resolution of the resolution solution obtained in this example with the sample size set to 20 μ l was 3.18 and the minimum signal-to-noise ratio of the sensitivity solution was 54.3, compared to the sample size set to 10 μ l (example 1).

Example 12

The detection wavelength in the chromatographic conditions set in the high performance liquid chromatography method is set to be 205nm, and other chromatographic conditions are the same as those in the embodiment 1;

the experimental procedure is as follows:

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

from the results of FIG. 14, it can be seen that the minimum resolution of the resolution solution obtained in this example was 4.08 and the minimum signal-to-noise ratio of the sensitivity solution was 42.0 when the detection wavelength was set to 205nm, compared to the wavelength set to 210nm (example 1).

Example 13

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

the experimental procedure is as follows:

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

from the results of fig. 15, it can be seen that the minimum resolution of the resolution solution obtained in this example with the detection wavelength set at 215nm was 4.09 and the minimum signal-to-noise ratio of the sensitivity solution was 35.5, compared to the forward wavelength set at 210nm (example 1).

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

table 7: summary of results for different chromatographic conditions

It should be understood that the above examples are only for clarity of illustration and are not intended to limit the embodiments. Other variations and modifications will be apparent to persons skilled in the art in light of the above description. And are neither required nor exhaustive of all embodiments. And obvious variations or modifications therefrom are within the scope of the invention.

Claims

1. A quality control method of nifuratel tablets is characterized in that the quality control method is high performance liquid chromatography.

2. A quality control method of nifuratel tablets according to claim 1, characterized in that the high performance liquid chromatography adopts octadecyl bonded silica gel chromatography column.

3. The quality control method of nifuratel tablets according to claim 1, characterized in that the high performance liquid chromatography mobile phase adopts water phase-organic phase mixing.

4. A quality control method of nifuratel tablets according to claim 3, characterized in that the organic phase in the flow of high performance liquid chromatography is acetonitrile.

5. A quality control method of nifuratel tablets according to claim 3, characterized in that, the mobile phase program is set to:

0min: the water phase is 90-70%, and the organic phase is 10-30%;

2min: the water phase is 90-70%, and the organic phase is 10-30%;

13min: the water phase is 50-30%, and the organic phase is 50-70%;

13.1min: the water phase is 90-70%, and the organic phase is 10-30%;

20min: the water phase is 90-70% and the organic phase is 10-30%.

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

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

8. The quality control method of nifuratel tablets according to claim 1, characterized in that the sample volume of the high performance liquid chromatography is 5-20 μ l.

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

10. A quality control method of nifuratel tablets according to any one of claims 1 to 9, characterized by comprising the following steps:

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

s3, comparison product solution: precisely measuring the oxidized impurities II, the oxidized impurities III, the impurities A, the impurities B, the impurities C and the nifuratel reference substance storage solution in the step S2, placing the reference substance storage solution into the same measuring flask, diluting the reference substance storage solution to a scale with a blank solution, shaking up the reference substance storage solution to obtain a reference substance solution, and injecting the sample under the set high performance liquid chromatography condition;