CN112557541B - Detection method of maropiptan citrate and related substances thereof - Google Patents

Abstract

The invention relates to the technical field of drug analysis, in particular to a method for detecting maropitant citrate and related substances. The detection method is high performance liquid chromatography. Through the optimization of the solvent of the solution to be tested and the chromatographic conditions, the effective separation between the main components and the known impurities can be achieved, and the qualitative and quantitative detection of maropitant citrate and its Impurities. The detection method of the invention has the advantages of good chromatographic peak separation effect, high sensitivity, good accuracy and reproducibility, simple method and convenient operation, which fills the blank in the detection field of maropitant citrate related substances. Good control of the quality of maropitant citrate products provides a reliable guarantee and has broad application prospects.

Description

A kind of detection method of maropitant citrate and related substances

technical field

The invention relates to the technical field of drug analysis, in particular to a method for detecting maropitant citrate and related substances.

Background technique

Maropitant citrate (English name: Maropitant Citrate; CAS number: 147116-67-4) is a neurokinin (NK1) receptor antagonist, which can block substance P (a neurotransmitter associated with vomiting) and Receptor binding can effectively inhibit central nervous system vomiting, peripheral nervous vomiting and vomiting caused by chemical factors. The drug approved for the market for the first time has the advantages of definite curative effect, fast absorption, high bioavailability, long-lasting efficacy and high safety, and has good clinical application value and market prospect.

Impurities such as starting materials, intermediates, and by-products may be introduced during the synthesis of maropitant citrate, so corresponding detection methods must be established to control the content of impurities to ensure the safety of medication. However, at present, the "US Pharmacopoeia", "European Pharmacopoeia", "Japanese Pharmacopoeia" and "Chinese Pharmacopoeia" do not include the detection methods for related substances of Maropitant citrate, nor have they detected relevant literature reports. Methods for the detection of ropitant related substances. However, related substances may have certain adverse effects on the safety of clinical application. Therefore, quality control of maropitant citrate is particularly important.

SUMMARY OF THE INVENTION

In view of the problem that there is no detection method for maropitant citrate related substances in the prior art, the present invention provides a detection method for maropitant citrate and related substances.

In order to achieve the above-mentioned purpose of the invention, the embodiment of the present invention adopts the following technical scheme:

A method for detecting maropitant citrate and its related substances, wherein a solution to be tested is prepared by using a methanol solution of 0.1-0.2% v/v triethylamine as a solvent, and high performance liquid chromatography is used to measure the related substances, The chromatographic conditions of the high performance liquid chromatography are:

Chromatographic column: octadecyl bonded silica column;

Mobile phase: mobile phase A is 0.005-0.015mol/L dipotassium hydrogen phosphate solution, and the pH value is adjusted to 7.30-7.70 with phosphoric acid; mobile phase B is acetonitrile; mobile phase C is methanol;

Gradient elution was carried out using mobile phase A, mobile phase B and mobile phase C, and the elution gradient was as follows:

The detection wavelength is 200～240nm;

The column temperature was 38-42°C.

The method for detecting maropitant citrate and related substances provided by the present invention can realize effective separation between main components and known impurities, and can accurately qualitatively and quantitatively detect maropitant citrate and its impurities. And through the methodological research and verification of specificity, sensitivity, etc., it is found that the detection method of the present invention has good chromatographic peak separation effect, high sensitivity, good accuracy and reproducibility, and the method is simple and convenient to operate, which fills the citric acid horse. The blank in the field of ropitant-related substance detection provides a reliable guarantee for improving and better controlling the quality of maropitant citrate products, and has broad application prospects.

Taking mobile phase A as an example, the elution gradient is specifically expressed as: 0min~7min, the volume percentage of mobile phase A decreases uniformly from 49~51% to 25%, and the volume percentage of mobile phase A decreases uniformly from 25% for 7min~9min To 21.5%, the volume percentage of mobile phase A increased from 21.5% to 49-51% at a constant speed in 30min-30.1min, and then remained at 49-51%

Preferably, the related substances include 2-benzylidenequinone, (2S)-2-benzylquinone, (2S,3S)-2-benzylquinonebenzylamine, (2S,3S)-2-benzylquinone-3-amine, 5-tert-butyl-2methoxybenzaldehyde and (2S,3S)-2-benzyl-N-(5 -tert-Butyl-2-methoxybenzyl)quinuclidin-3-imine. The above impurities are impurities introduced or degraded in the synthesis process of maropitant citrate.

Preferably, the elution gradient is as follows:

Preferably, the flow rate is 1.0 ml/min.

Preferably, the detection wavelength is 222 nm.

Preferably, the column temperature is 40°C.

Preferably, the pH of the mobile phase A is 7.50.

Preferably, the concentration of dipotassium hydrogen phosphate in the dipotassium hydrogen phosphate solution is 0.01 mol/L.

Preferably, the solution to be tested is prepared with 0.2% v/v triethylamine in methanol as a solvent.

Preferably, the chromatographic column is CAPCELL PAK C18, the specification is: 4.6×250 mm, and the particle size of the filler is 5 μm.

Preferably, the detection method comprises the following steps:

Step a, prepare the reference substance solution of at least five concentrations of need testing solution and Maropitant citrate and related substances thereof;

Step b, using the high performance liquid chromatography to measure the reference substance solution to obtain a linear regression equation;

Step c, use the high performance liquid chromatography to measure the test solution, and use the linear regression equation obtained in step b to calculate the content of maropitant citrate and related substances in the test solution.

The beneficial effects of the invention are: high specificity of chromatographic conditions, stable system, good linearity, high precision, high accuracy, good durability test, and can effectively measure maropitant citrate and related substances.

Description of drawings

Fig. 1 is the chromatogram of the system suitability solution under the system suitability item in the embodiment 1;

Fig. 2 is the chromatogram of need testing solution under the specificity item in embodiment 1;

Fig. 3 is the chromatogram of the detection limit solution under the detection limit limit item in embodiment 1;

Fig. 4 is the chromatogram of the quantification limit solution under the detection limit limit in Example 1.

Detailed ways

In order to make the objectives, technical solutions and advantages of the present invention clearer, the present invention will be further described in detail below with reference to the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention, but not to limit the present invention.

In the following examples, impurity A refers to 2-benzylidenequinone, impurity B refers to (2S)-2-benzylquinone, and impurity C refers to (2S,3S)-2-diphenylmethylquinone Benzylquinone benzylamine, impurity D refers to (2S,3S)-2-benzylquinone-3-amine, impurity E refers to 5-tert-butyl-2methoxybenzaldehyde, Impurity F refers to (2S,3S)-2-benzyl-N-(5-tert-butyl-2-methoxybenzyl)quinuclidine-3-imine.

Instruments: high performance liquid chromatograph, diode array detector, measuring flask, electronic balance.

Blank solvent: 0.2% v/v triethylamine in methanol.

Example 1

The embodiments of the present invention provide a method for detecting maropitant citrate and related substances thereof.

1.1 Preparation of the solution

Preparation of each impurity stock solution: respectively take appropriate amount of impurity A, impurity B, impurity C, impurity D, impurity E, impurity F reference substance, accurately weigh, add 0.2% v/v methanol solution of triethylamine to dissolve and dilute A stock solution of each impurity was prepared containing approximately 0.08 mg in 1 mL.

Preparation of the test solution: take an appropriate amount of maropitant citrate to be tested, add 0.2% v/v triethylamine in methanol solution to dissolve and dilute to make 1 mL containing 0.4 mg/v of maropitant citrate. ml of the test article.

Preparation of reference substance primary stock solution: Precisely measure 2.0ml of each reference substance, put it in a 10mL volumetric flask, dissolve it with 0.2% v/v triethylamine methanol solution to the mark, shake well, and use it as each reference substance Primary stock solution.

Mixed reference substance solution: Precisely measure Maropitant citrate reference substance primary stock solution, impurity A, impurity B, impurity C, impurity D, impurity E, impurity F impurity stock solution appropriate amount, use 0.2% v/ The methanol solution of v triethylamine is diluted to prepare a mixed solution containing maropitant citrate, impurity A, impurity B, impurity C, impurity D, impurity E, and impurity F with a content of 0.8 μg/ml.

The preparation of each impurity and Maropitant citrate positioning solution: Precisely measure the first-level stock solution of Maropitant citrate reference substance, impurity A, impurity B, impurity C, impurity D, impurity E, impurity F An appropriate amount of each impurity stock solution was diluted with a methanol solution of 0.2% v/v triethylamine to prepare Maropitant citrate, impurity A, impurity B, impurity C, impurity D, impurity E, and impurity F. The contents are: 0.8 μg/ml of positioning solution.

1.2 Conditions of high performance liquid chromatography:

Chromatographic column: CAPCELL PAK C18 (4.6×250mm) 5μm;

Flow rate: 1.0ml/min;

Detection wavelength: 222nm;

Column temperature: 40℃;

Test solution concentration: 0.4mg/ml;

Injection volume: 20μl;

Mobile phase A phase: 0.01mol/L dipotassium hydrogen phosphate solution (pH7.50), the preparation method is: take 2.28g of dipotassium hydrogen phosphate, add 900ml of water to dissolve, adjust the pH to 7.50 with phosphoric acid, add water to 1000ml, Shake well, filter and get it;

Mobile phase B phase: acetonitrile;

Mobile Phase Phase C: Methanol.

Elute according to the following gradient program:

time (min) Mobile phase A (%) Mobile phase B (%) Mobile phase C (%) 0 50 45 5 7 25 70 5 9 21.5 73.5 5 30 21.5 73.5 5 30.1 50 45 5 50 50 45 5

1.3 Methodological validation:

1. System suitability

Take the blank solvent and mixed reference solution (ie system suitability solution) for sample injection and detection, in which the system suitability solution is continuously injected into 6 needles, and the sample is injected and detected according to the high performance liquid chromatography conditions of 1.2, the injection volume is 20 μl, and the chromatogram is recorded. ,As shown in Figure 1. The test results data are shown in Table 1.

Table 1 System suitability test results

It can be seen from Figure 1 that the baseline is stable without interference, and the blank solvent has no interference with the detection of impurities and main components; as can be seen from the data in Table 1, the peak areas of impurities A, B, C, D, E, F and maropitant citrate The RSD value of the retention time is less than 2%, which is in line with the requirements, and the separation degree of each impurity and the main peak Maropitant citrate is in compliance with the regulations, which is suitable for the inspection of related substances.

The test results show that the method has good system applicability.

2. Exclusivity

Take blank solvent, impurity locating solution, test solution and mixed reference solution respectively according to the high performance liquid chromatography conditions of 1.2, inject 20μl, record the chromatogram, the chromatogram of the test solution is shown in Figure 2 The test result data of the test solution is shown in Table 2, and the test result data of the mixed control solution is shown in Table 3.

Table 2 Test results of the test solution

name Retention time (min) Peak area degree of separation Impurity B 8.030 9787 - Impurity C 13.940 26386 13.267 Impurity E 10.392 2160 11.265 Maropitant Citrate 25.637 17523974 23.889

Impurities A, D and F were not detected in the test product.

Table 3 Test results of mixed reference solution

The test results show that the minimum resolution between each impurity peak and between each impurity peak and maropitant citrate is greater than 1.5, and there is no interference between each impurity and between each impurity and maropitant citrate, indicating that The specificity of this method is good.

3. Limit of detection and limit of quantification

Take each impurity stock solution and the reference substance primary stock solution solution of maropitant citrate, and measure the limit of quantification (S/N≥10) and detection limit (S/N≥3) by dilution method, respectively. The chromatogram of the solution is shown in Figure 3, and the chromatogram of the limit of quantification solution is shown in Figure 4. The test results are shown in Table 4.

Table 4 Detection limit and quantification limit test results

sample Limit of Quantitation (μg/mL) Detection limit concentration (μg/mL) Impurity A 0.096 0.032 Impurity B 0.100 0.033 Impurity C 0.185 0.061 Impurity D 0.160 0.053 Impurity E 0.040 0.013 Impurity F 0.295 0.097 Maropitant 0.320 0.106

The test results showed that the detection limit concentrations of impurities A, B, C, D, E, F and maropitant citrate were 0.096 μg/mL, 0.100 μg/mL, 0.185 μg/mL, 0.160 μg/mL, 0.040μg/mL, 0.295μg/mL, 0.320μg/mL; the limit of quantification concentrations were 0.032μg/mL, 0.033μg/mL, 0.061μg/mL, 0.053μg/mL, 0.013μg/mL, 0.097μg/mL, 0.106 μg/mL. The test results show that the method has high sensitivity.

4. Linear range

Precisely weigh the appropriate amount of impurity A, impurity B, impurity C, impurity D, impurity E and impurity F, dissolve and dilute with blank solvent respectively to make the concentration of 1.60μg/mL, 1.20μg/mL, 0.96μg/mL, 0.80μg /mL, 0.64 μg/mL, 0.40 μg/mL series of concentration solutions.

Precisely weigh an appropriate amount of Maropitant citrate reference substance, dissolve and dilute with blank solvent to prepare the concentration of 2.320μg/mL, 1.740μg/mL, 1.392μg/mL, 1.160μg/mL, 0.928μg/mL, A range of concentration solutions of 0.580 μg/mL.

Precisely measure 20 μL of each of the above-mentioned reference substance solutions and inject them into the high-performance liquid chromatograph respectively, inject and detect according to the high-performance liquid chromatography conditions of 1.2, record the chromatogram, and measure the peak area, taking the peak area A as the ordinate and the concentration C as the abscissa A linear regression was performed, and the results are shown in Table 5.

Table 5 Linear Results

sample Linear equation R² Linear range (μg/ml) Impurity A y=40569x+880.95 0.9997 0.40～1.60 Impurity B y=38108x+431.93 0.9999 0.40～1.60 Impurity C y=36102x+32.493 0.9996 0.40～1.60 Impurity D y=25049x-122.54 0.9992 0.40～1.60 Impurity E y=102379x+3325.8 0.9998 0.40～1.60 Impurity F y=57808x-2403.4 0.9996 0.40～1.60 Maropitant Citrate y=33020x+1381 0.9995 0.58～2.32

The above results show that the R ² of impurity A, impurity B, impurity C, impurity D, impurity E and impurity F are 0.9997, 0.9999, 0.9996, 0.9992, 0.9998 and 0.9996 respectively in the concentration range of 0.40-1.60 μg/ml. In the concentration range of 0.58-2.32 μg/ml, R ² =0.9995 for maropitant, indicating that the method has a good linear relationship between the concentration and the peak area.

5. Accuracy

50% test solution: weigh 29 mg of maropitant citrate and dissolve in methanol solution of 0.2% v/v triethylamine, take impurity A, impurity B, impurity C, impurity D, impurity E, impurity F respectively The first-level stock solution of the reference substance is appropriate, add 0.2% v/v triethylamine in methanol solution to make 0.4 μg/mL of impurity A, impurity B, impurity C, impurity D, impurity E, impurity F, citric acid Maropitant 0.4mg/mL solution is obtained.

100% test solution: Weigh 29 mg of maropitant citrate and add diluent to dissolve, respectively take an appropriate amount of the reference substance primary stock solution of impurity A, impurity B, impurity C, impurity D, impurity E, and impurity F, The methanol solution of 0.2% v/v triethylamine was added to prepare a solution containing impurity A, impurity B, impurity C, impurity D, impurity E, impurity F each 0.8 μg/mL, and maropitant citrate 0.4 mg/mL. solution, that is.

150% test solution: weigh 29 mg of maropitant citrate and dissolve it in a diluent, take an appropriate amount of the reference substance primary stock solution of impurity A, impurity B, impurity C, impurity D, impurity E, and impurity F respectively, Add the methanol solution of 0.2% v/v triethylamine to make the solution containing impurity A, impurity B, impurity C, impurity D, impurity E, impurity F each 1.2μg/mL, maropitant citrate 0.4mg/mL. solution, that is.

According to the above preparation method, three samples were prepared in parallel for each concentration for determination.

Precisely measure 20 μL of each of the above solutions, inject them into a liquid chromatograph, inject and detect according to the high performance liquid chromatography conditions of 1.2, and record the chromatogram. The results are shown in Table 6 below.

Table 6 Recovery test results

The above results show that the recovery rate of each impurity at each concentration is in the range of 92-105%, and the RSD value is all less than 2%, indicating that the accuracy of this method is good.

Example 2

The present embodiment provides a method for detecting maropitant citrate and related substances thereof, and the conditions of high performance liquid chromatography:

Chromatographic column: CAPCELL PAK C18 (4.6×250mm) 5μm;

Flow rate: 1.0ml/min;

Detection wavelength: 222nm;

Column temperature, 38℃;

Test solution concentration: 0.4mg/ml;

Injection volume: 20μl;

Mobile phase A phase: 0.01mol/L dipotassium hydrogen phosphate solution (pH7.50), the preparation method is the same as in Example 1;

Mobile phase B phase: acetonitrile;

Mobile Phase Phase C: Methanol.

The gradient program conditions were the same as in Example 1.

Precisely measure 20 μL of each 20 μL of blank solvent and the mixed reference solution and the need-testing solution of Example 1, inject into the liquid chromatograph respectively, and measure according to the above-mentioned high-performance liquid chromatography conditions, record the peak area of each component and record the chromatogram. The results are shown in Table 7, Table 8.

Table 7 mixed control solution detection results

mixed control solution retention time min degree of separation Impurity A 9.319 6.149 Impurity B 8.131 18.37 Impurity C 13.853 12.394 Impurity D 4.614 - Impurity E 10.56 6.076 Impurity F 28.97 4.346 Maropitant Citrate 25.811 23.338

Table 8 Test results of related substances in the test solution

Test solution retention time min degree of separation Impurity B 8.128 — Impurity C 13.862 11.610 Impurity E 10.576 11.146 Maropitant Citrate 25.778 23.412

Example 3

The present embodiment provides a method for detecting maropitant citrate and related substances thereof, and the conditions of high performance liquid chromatography:

Chromatographic column: CAPCELL PAK C18 (4.6×250mm) 5μm;

Flow rate: 1.0ml/min;

Detection wavelength: 222nm;

Column temperature, 42°C;

Test solution concentration: 0.4mg/ml;

Injection volume: 20μl;

Mobile phase A phase: 0.01mol/L dipotassium hydrogen phosphate solution (pH7.50), the preparation method is the same as in Example 1;

Mobile phase B phase: acetonitrile;

Mobile Phase Phase C: Methanol.

The gradient elution conditions were the same as in Example 1.

Precisely measure 20 μL of each 20 μL of blank solvent and the mixed reference solution and the need-testing solution of Example 1, inject into the liquid chromatograph respectively, and measure according to the above-mentioned high-performance liquid chromatography conditions, record the peak area of each component and record the chromatogram. The results are shown in Table 9, Table 10.

Table 9 mixed control solution detection results

mixed control solution retention time min degree of separation Impurity A 9.163 5.089 Impurity B 8.064 14.889 Impurity C 13.965 12.087 Impurity D 4.803 — Impurity E 10.367 5.245 Impurity F 28.432 3.846 Maropitant Citrate 25.543 21.273

Table 10 Test results of related substances in the test solution

Test solution retention time min degree of separation Impurity B 8.050 — Impurity C 13.962 11.064 Impurity E 10.370 8.499 Maropitant Citrate 25.505 20.177

Example 4

The present embodiment provides a method for detecting maropitant citrate and related substances thereof, and the conditions of high performance liquid chromatography:

Chromatographic column: CAPCELL PAK C18 (4.6×250mm) 5μm;

Flow rate: 1.0ml/min;

Detection wavelength: 222nm;

Column temperature, 40℃;

Test solution concentration: 0.4mg/ml;

Injection volume: 20μl;

Mobile phase A phase: 0.01mol/L dipotassium hydrogen phosphate solution (pH7.50), the preparation method is the same as in Example 1;

Mobile Phase Phase B: Acetonitrile,

Mobile Phase Phase C: Methanol.

Elute according to the following gradient program:

time (min) Mobile phase A (%) Mobile phase B (%) Mobile phase C (%) 0 49 46 5 7 25 70 5 9 21.5 73.5 5 30 21.5 73.5 5 30.1 49 46 5 50 49 46 5

Precisely measure 20 μL of each 20 μL of blank solvent and the mixed reference solution and the need-testing solution of Example 1, inject into the liquid chromatograph respectively, and measure according to the above-mentioned high-performance liquid chromatography conditions, record the peak area of each component and record the chromatogram. The results are shown in Table 11, Table 12.

Table 11 Test results of mixed control solution

Table 12 Test results of related substances in the test solution

Test solution retention time min degree of separation Impurity B 7.963 - Impurity C 13.792 15.008 Impurity E 10.417 12.717 Maropitant Citrate 25.689 28.585

Example 5

The present embodiment provides a method for detecting maropitant citrate and related substances thereof, and the conditions of high performance liquid chromatography:

Chromatographic column: CAPCELL PAK C18 (4.6×250mm) 5μm;

Flow rate: 1.0ml/min;

Detection wavelength: 222nm;

Column temperature, 40℃;

Test solution concentration: 0.4mg/ml;

Injection volume: 20μl;

Mobile phase A phase: 0.01mol/L dipotassium hydrogen phosphate solution (pH7.50), the preparation method is the same as in Example 1;

Mobile phase B phase: acetonitrile;

Mobile Phase Phase C: Methanol.

Elute according to the following gradient program:

time (min) Mobile phase A (%) Mobile phase B (%) Mobile phase C (%) 0 51 44 5 7 25 70 5 9 21.5 73.5 5 30 21.5 73.5 5 30.1 51 44 5 50 51 44 5

Precisely measure 20 μL of each 20 μL of blank solvent and the mixed reference solution and the need testing solution of Example 1, inject into the liquid chromatograph respectively, and measure according to the above-mentioned high-performance liquid chromatography conditions, record the peak area of each component and record the chromatogram. The results are shown in Table 13, Table 14.

Table 13 Test results of mixed control solution

mixed control solution retention time min degree of separation Impurity A 9.369 6.672 Impurity B 8.240 21.676 Impurity C 13.957 14.791 Impurity D 4.621 - Impurity E 10.593 6.998 Impurity F 29.008 5.101 Maropitant Citrate 25.881 27.830

Table 14 Test results of related substances in the test solution

Test solution retention time min degree of separation Impurity B 8.193 — Impurity C 13.953 15.058 Impurity E 10.584 12.587 Maropitant Citrate 25.836 28.439

The above descriptions are only preferred embodiments of the present invention and are not intended to limit the present invention. Any modifications, equivalent replacements and improvements made within the spirit and principles of the present invention shall be included in the protection of the present invention. within the range.

Claims (8)

1. A detection method of maririptan citrate and related substances thereof is characterized in that a methanol solution of 0.1-0.2% v/v triethylamine is used as a solvent to prepare a solution to be detected, and a high performance liquid chromatography is used for detecting the related substances, wherein the chromatographic conditions of the high performance liquid chromatography are as follows:

and (3) chromatographic column: octadecyl bonding silica gel column;

mobile phase: the mobile phase A is 0.005-0.015 mol/L dipotassium hydrogen phosphate solution, and the pH value is adjusted to 7.30-7.70 by using phosphoric acid; the mobile phase B is acetonitrile; the mobile phase C is methanol;

and (3) carrying out gradient elution by adopting the mobile phase A, the mobile phase B and the mobile phase C, wherein the elution gradient is as follows:

the detection wavelength is 200-240 nm;

the column temperature is 38-42 ℃;

the related substances include 2-benzylidene quinuclidinone, (2S) -2-benzhydryl quinuclidinone, (2S,3S) -2-benzhydryl quinuclidinone benzylamine, (2S,3S) -2-benzhydryl quinuclidinone-3-amine, 5-tert-butyl-2 methoxybenzaldehyde and (2S,3S) -2-benzhydryl-N- (5-tert-butyl-2-methoxybenzyl) quinuclidin-3-imine.

2. The method for detecting maririptan citrate and related substances according to claim 1, wherein the elution gradient is as follows:

3. the method for detecting maririptan citrate and related substances according to claim 1, wherein the flow rate is 1.0 ml/min; and/or

The detection wavelength is 222 nm; and/or

The column temperature was 40 ℃.

4. The method for detecting maririptan citrate and related substances according to claim 1, wherein the pH value of the mobile phase A is 7.50.

5. The method for detecting maririptan citrate and related substances according to claim 1, wherein the concentration of dipotassium hydrogen phosphate in the dipotassium hydrogen phosphate solution is 0.01 mol/L.

6. The method for detecting maririptan citrate and related substances according to claim 1, wherein a methanol solution of 0.2% v/v triethylamine is used as a solvent to prepare a solution to be detected.

7. The method for detecting maririptan citrate and related substances according to claim 1, wherein the chromatographic column is CAPCELL PAK C18, and the specification is as follows: 4.6X 250mm, filler particle size 5 μm.

8. The detection method of maririptan citrate and related substances according to any one of claims 1 to 7, characterized by comprising the following steps:

step a, preparing a test solution and at least five concentrations of control solutions of the citric acid maropiptan and related substances thereof;

b, measuring the reference substance solution by using the high performance liquid chromatography to obtain a linear regression equation;

and c, measuring the test solution by using the high performance liquid chromatography, and calculating the contents of the maririptan citrate and related substances in the test solution by using the linear regression equation obtained in the step b.

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