A method for detecting bilastine-related substances

Abstract

The invention solves the problems existing in the prior art and provides a method for detecting bilastine-related substances, which can achieve good separation between impurities and between impurities and a main peak, and effectively control the quality of bilastine.

Description

Technical Field

[0001] The invention belongs to the technical field of drug analysis, and in particular relates to a method for detecting bilastine-related substances. Background Art

[0002] Bilastine is a non-sedating, long-acting antihistamine that selectively antagonizes peripheral H1 receptors and is used to treat allergic rhinoconjunctivitis (seasonal and perennial) and urticaria. It was first approved for marketing by the EU in August 2010. Currently, the dosage forms approved for marketing in the EU include tablets, orally disintegrating tablets, and oral solutions.

[0003] Bilastin, CAS No.: 202189-78-4, chemical name is 2-[4-(2-{4-[1-(2-ethoxyethyl)-1H-benzimidazol-2-yl]-1-piperidinyl}ethyl)phenyl]-2-methylpropanoic acid, the structural formula is as follows:

[0004] .

[0005] During the preparation and storage of bilastine, side reaction impurities and degradation products may be generated. In order to ensure the quality of bilastine, a scientific analytical method is needed to detect and control the various impurities therein. CN116165307A provides a method for separating bilastine raw materials and impurities thereof, but does not involve the detection of oxidative degradation impurities, and it can be seen in the spectrum that impurities and the main peak are not baseline separated. CN118483338A provides a method for separating bilastine oral solution and impurities thereof, but only involves the detection of oxidative degradation impurities, and does not involve other degradation impurities during the preparation and storage of bilastine. CN116263435A provides a method for simultaneously separating and determining bilastine and its related impurities in bilastine tablets, but does not mention the separation of enantiomers. Therefore, it is very necessary to establish a stable and effective method for detecting related substances of bilastine. Summary of the invention

[0006] The invention solves the problems existing in the prior art, provides a stable and effective method for detecting bilastine-related substances, can achieve good separation between various side reaction impurities and degradation products and between impurities and main peaks, and effectively control the quality of bilastine.

[0007] The invention provides a method for detecting bilastine-related substances, comprising the following steps: respectively sampling a separation solution and a test solution, detecting according to high performance liquid chromatography conditions, and recording a chromatogram; the chromatographic conditions are: a chromatographic column: a chromatographic column with octadecylsilane bonded silica gel as a filler; a mobile phase: a mobile phase A is a buffer solution and an organic solvent, a mobile phase B is an organic solvent, and gradient elution is performed according to the following table:

[0008] .

[0009] Wherein, the related substances include the following structures:

[0010] .

[0011] The chromatographic conditions also include:

[0012] Detector: UV detector;

[0013] Flow rate: 1.0ml / min;

[0014] Column temperature: 25~35℃, preferably 30℃;

[0015] Detection wavelength: 275nm;

[0016] Injection volume: 10 μl.

[0017] The chromatographic column of the present invention is selected from Inertsil ODS-3 C18 4.6mm×250mm 5μm, AgilentZORBAX Eclipse XDB-C18 4.6mm×250mm 5μm, Waters Xbridge C18 250mm×4.6mm, 5μm, preferably Inertsil ODS-3 C18, 4.6mm×250mm, 5μm or a chromatographic column with equivalent performance.

[0018] The buffer solution in the mobile phase A of the present invention is a phosphate buffer solution, which can be selected from one or more of potassium dihydrogen phosphate solution, ammonium dihydrogen phosphate solution, sodium dihydrogen phosphate solution, and calcium dihydrogen phosphate solution. Preferably, the buffer solution is potassium dihydrogen phosphate solution. The concentration of the phosphate buffer solution is 5 to 50 mmol / L, preferably 10 mmol / L.

[0019] Furthermore, the phosphate buffer is adjusted to a pH value of 6.7 to 7.1 with an alkaline agent; preferably, the pH value is 6.9. The alkaline agent is selected from one or more of sodium hydroxide, potassium hydroxide, and ammonia water; preferably sodium hydroxide; the concentration of the alkaline agent is 1 mol / L.

[0020] The organic solvent in the mobile phase A of the present invention is selected from one or more of acetonitrile, methanol, tetrahydrofuran and isopropanol; preferably, methanol and acetonitrile.

[0021] Furthermore, the volume ratio of the buffer solution to the organic solvent in the mobile phase A of the present invention is 75-65:25-35; preferably, the volume ratio is 70:30.

[0022] Furthermore, the mobile phase A described in the present invention is potassium dihydrogen phosphate solution, methanol and acetonitrile; wherein the volume ratio of the potassium dihydrogen phosphate solution: methanol: acetonitrile is 70:15:15.

[0023] The organic solvent in the mobile phase B of the present invention is selected from one or more of acetonitrile, methanol, tetrahydrofuran, and isopropanol; preferably methanol and acetonitrile. The volume ratio of methanol to acetonitrile is 35-65:65-35; preferably, the volume ratio of methanol to ethanol is 50:50.

[0024] The separation solution is prepared by the following process: taking an appropriate amount of each impurity reference substance, adding a solvent to dissolve and dilute, shaking well, and using each impurity location solution as each impurity location solution; taking an appropriate amount of bilastine, adding a solvent to dissolve, and then adding an appropriate amount of each impurity location solution, diluting with a solvent and shaking well to obtain the solution.

[0025] The test solution is prepared by the following process: taking an appropriate amount of bilastine, adding a solvent to dissolve it, diluting it and shaking it well. The solvent is acetonitrile and 0.15% phosphoric acid solution, and the volume ratio is 20:80.

[0026] The present invention further provides a method for detecting bilastine-related substances, comprising the following steps: respectively sampling a separation solution and a test solution, detecting according to high performance liquid chromatography conditions, and recording a chromatogram; the chromatographic conditions are: chromatographic column: Inertsil ODS-3 C18, 4.6 mm × 250 mm, 5 μm or a chromatographic column with equivalent performance; mobile phase: mobile phase A is potassium dihydrogen phosphate solution, methanol and acetonitrile, mobile phase B is methanol and acetonitrile, and gradient elution is performed according to the following table:

[0027] ;

[0028] Wherein, the related substances include the following structures:

[0029] ;

[0030] The chromatographic conditions also include:

[0031] Detector: UV detector;

[0032] Flow rate: 1.0ml / min;

[0033] Column temperature: 30°C;

[0034] Detection wavelength: 275nm;

[0035] Injection volume: 10 μl.

[0036] The potassium dihydrogen phosphate solution in the mobile phase A is adjusted to pH 6.9 with 1 mol / L sodium hydroxide solution, and its concentration is 10 mmol / L. The volume ratio of the potassium dihydrogen phosphate solution, methanol, and acetonitrile is 70:15:15.

[0037] The volume ratio of methanol to acetonitrile in the mobile phase B is 50:50.

[0038] The separation solution is prepared by the following process: impurity A positioning solution: accurately weigh 1.387 mg of impurity A reference substance, put it in a 10 ml volumetric bottle, add a solvent to dissolve and dilute to the scale, shake well, and obtain; related substance A positioning solution: accurately weigh 0.924 mg of related substance A reference substance, put it in a 10 ml volumetric bottle, add a solvent to dissolve and dilute to the scale, shake well, and obtain; impurity B positioning solution: accurately weigh 1.012 mg of impurity B reference substance, put it in a 10 ml volumetric bottle, add a solvent to dissolve and dilute to the scale, shake well, and obtain; impurity C positioning solution: accurately weigh 0.962 mg of impurity C reference substance, put it in a 10 ml volumetric bottle, add a solvent to dissolve and dilute to the scale, shake well, and obtain; impurity D positioning solution: accurately weigh impurity 0.979 mg of quality D reference substance is placed in a 10 ml volumetric flask, dissolved in solvent and diluted to the scale, shake well to obtain; impurity E positioning solution: accurately weigh 1.025 mg of impurity E reference substance, place in a 10 ml volumetric flask, dissolve in solvent and dilute to the scale, shake well to obtain; impurity F positioning solution: accurately weigh 1.095 mg of impurity F reference substance, place in a 10 ml volumetric flask, dissolve in solvent and dilute to the scale, shake well to obtain; separation solution: accurately weigh 50.49 mg of bilastine reference substance, place in a 50 ml volumetric flask, add an appropriate amount of solvent to dissolve it by ultrasound, add 2 ml of the above-mentioned impurity A positioning solution, 1 ml each of impurity B, impurity C, impurity D, impurity E and impurity F positioning solutions, dilute to the scale with solvent and shake well.

[0039] The test solution is prepared by the following process: take about 50 mg of bilastine, put it in a 50 ml volumetric bottle, add an appropriate amount of solvent, ultrasonically shake for 10 minutes to dissolve the bilastine, cool it, dilute it to the scale with the solvent, shake it well, filter it, and take the filtrate.

[0040] The solvent is acetonitrile and 0.15% phosphoric acid solution, and the volume ratio thereof is 20:80.

[0041] The present invention further provides a method for detecting bilastine-related substances and its use in quality control of bilastine.

[0042] The beneficial technical effects of the present invention are:

[0043] (1) The detection method provided by the present invention can effectively control the process impurities and degradation impurities in bilastine, and the detection method has good impurity separation, specificity, sensitivity and durability.

[0044] (2) The chromatographic conditions of the detection method provided by the present invention are easy to obtain, have no special requirements, and are convenient to operate. BRIEF DESCRIPTION OF THE DRAWINGS

[0045] Figure 1 This is the chromatogram of the screening test under condition ② of Example 1.

[0046] Figure 2 This is the chromatogram of the screening test under condition ③ of Example 1.

[0047] Figure 3 The chromatogram is the chromatogram of the screening test under condition ④ of Example 1.

[0048] Figure 4 This is an overlay diagram of the blank solvent interference test for related substance inspection in Example 2.

[0049] Figure 5 This is a solution chromatogram showing the separation of the related substances in Example 3.

[0050] Figure 6 This is an overlay diagram of the recovery rate test of related substances in Example 5.

[0051] Figure 7 This is an overlay diagram of the repeatability test of the related substance inspection in Example 6. DETAILED DESCRIPTION

[0052] Specific embodiments of the present invention are described in detail below. It should be noted that the embodiments described below are exemplary and are only used to explain the present invention, and should not be construed as limiting the present invention.

[0053] Instruments and conditions:

[0054] Instrument: Agilent 1260 high performance liquid chromatograph, UV detector (detection wavelength 275 nm);

[0055] Chromatographic column: a column filled with octadecylsilane bonded silica gel, preferably Inertsil ODS-3 C18, 4.6mm×250mm, 5μm or a column with equivalent performance;

[0056] Mobile phase: Mobile phase A: 10mmol / L potassium dihydrogen phosphate solution-methanol-acetonitrile (70:15:15); Mobile phase B: methanol-acetonitrile; Gradient elution program:

[0057] ;

[0058] Flow rate: 1.0ml / min;

[0059] Injection volume: 10 μl.

[0060] Solution preparation:

[0061] Test solution: Take about 50 mg of bilastine and place it in a 50 ml volumetric flask, add an appropriate amount of solvent, and shake ultrasonically for 10 minutes to dissolve the bilastine. Cool, dilute to the scale with solvent, shake well, filter, and take the filtrate.

[0062] Reference solution: Take an appropriate amount of bilastine reference substance, weigh accurately, dissolve in solvent and quantitatively dilute to make a solution containing about 2 μg per 1 ml.

[0063] Sensitivity solution: Accurately measure an appropriate amount of the reference solution and quantitatively dilute it with a solvent to make a solution containing approximately 0.5 μg per 1 ml.

[0064] System suitability solution: Take appropriate amounts of impurity A reference substance, impurity B reference substance, impurity C reference substance, impurity D reference substance, impurity E reference substance, impurity F reference substance and bilastine reference substance, dissolve in solvent and dilute to prepare a mixed solution containing approximately 2 μg of each impurity and 1 mg of bilastine per 1 ml.

[0065] Impurity A positioning solution: Accurately weigh 1.387 mg of impurity A reference substance, place in a 10 ml volumetric flask, add solvent to dissolve and dilute to the scale, shake well, and obtain.

[0066] Related substance A positioning solution: Accurately weigh 0.924 mg of related substance A reference substance, place in a 10 ml volumetric flask, add solvent to dissolve and dilute to the scale, shake well, and obtain.

[0067] Impurity B localization solution: Accurately weigh 1.012 mg of impurity B reference substance, place in a 10 ml volumetric flask, add solvent to dissolve and dilute to the scale, shake well, and obtain.

[0068] Impurity C positioning solution: Accurately weigh 0.962 mg of impurity C reference substance, place in a 10 ml volumetric flask, add solvent to dissolve and dilute to the scale, shake well, and obtain.

[0069] Impurity D localization solution: Accurately weigh 0.979 mg of impurity D reference substance, place in a 10 ml volumetric flask, add solvent to dissolve and dilute to the scale, shake well, and obtain.

[0070] Impurity E localization solution: Accurately weigh 1.025 mg of impurity E reference substance, place in a 10 ml volumetric flask, add solvent to dissolve and dilute to the scale, shake well, and obtain.

[0071] Impurity F localization solution: Accurately weigh 1.095 mg of impurity F reference substance, place in a 10 ml volumetric flask, add solvent to dissolve and dilute to the scale, shake well, and obtain.

[0072] Separation solution: Accurately weigh 50.49 mg of bilastine reference substance, place in a 50 ml volumetric flask, add an appropriate amount of solvent and sonicate to dissolve, add 2 ml of the above-mentioned impurity A location solution, 1 ml each of the impurity B, impurity C, impurity D, impurity E, and impurity F location solutions, dilute to the scale with solvent, and shake well.

[0073] Example 1 Screening of Chromatographic Conditions

[0074] Based on the above instruments and chromatographic conditions, continue to screen the most suitable chromatographic conditions.

[0075] Condition ① Selection of solvent

[0076] When the solvent is methanol, in an acidic environment, bilastine easily reacts with methanol to form bilastine impurity H, whose structure is: Therefore, the solvent was replaced with acetonitrile-0.15% phosphoric acid solution (20:80).

[0077] Condition ② Selection of mobile phase B

[0078] Screen the proportion of methanol in mobile phase B, accurately measure 10μl of the test solution, inject it into the liquid chromatograph, record the chromatogram, and the results are shown in Figure 1 It can be seen that the proportion of methanol in the organic phase has a great influence on the peak of impurities. When the proportion of methanol is reduced, the separation between impurity A and impurity B, impurity E and impurity F, and impurity C and related substance A all become worse. The optimal condition is that the proportion of methanol in the organic phase is 35%-65%, preferably 50%.

[0079] Condition ③ Selection of mobile phase A

[0080] Screen the pH value of the buffer salt in mobile phase A to observe its effect on the separation of impurities. Accurately measure 10µl of the test solution, inject it into the liquid chromatograph, and record the chromatogram. The results are shown in Figure 2 It can be seen that the pH value of the buffer salt has a great influence on the separation of impurities, and the optimal condition is that the pH value of the buffer salt is 6.6-7.1, preferably 6.9.

[0081] Condition ④ Selection of column temperature

[0082] Under the same chromatographic conditions, change the column temperature to observe its effect on the separation of impurities. Accurately measure 10μl of the test solution, inject it into the liquid chromatograph, and record the chromatogram. The results are shown in Figure 3 It can be seen that temperature has a significant effect on the separation between impurity C and related substance A. The lower the column temperature, the better the separation between impurity C and related substance A. Considering that low column temperature has high requirements on instruments and environment, the preferred column temperature is 30°C.

[0083] Example 2 Blank solvent interference test

[0084] Based on the preferred chromatographic conditions in Example 1, confirmatory experiments were continued.

[0085] Take 10 μl of blank solvent and separation solution, inject into liquid chromatograph, and record the chromatogram. Figure 4 The results showed that the blank solvent did not interfere with the detection of related substances.

[0086] Example 3 Separation Test

[0087] Take 10 μl of each impurity location solution and separation solution, inject it into the liquid chromatograph, and record the chromatogram. The results are shown in Table 1 and Figure 5 The results showed that the separation between the main peak and the adjacent impurity peaks was greater than 1.5, and the separation between each impurity peak was greater than 1.2, which met the acceptance criteria.

[0088] Table 1 Impurity location and separation test results

[0089]

[0090] Example 4 Quantitation limit and detection limit test

[0091] Impurity A stock solution: Accurately weigh 6.486 mg of impurity A reference substance, place it in a 25 ml volumetric flask, add solvent to dissolve and dilute to the scale, and shake well.

[0092] Impurity E stock solution: Accurately weigh 5.231 mg of impurity E reference substance, place in a 50 ml volumetric flask, add solvent to dissolve and dilute to the scale, and shake well.

[0093] Impurity F stock solution: Accurately weigh 5.549 mg of impurity F reference substance, place in a 50 ml volumetric flask, add solvent to dissolve and dilute to the scale, and shake well.

[0094] Bilastine stock solution: Accurately weigh 19.950 mg of bilastine working reference substance, place it in a 100 ml volumetric flask, add solvent to dissolve and dilute to the scale, and shake well.

[0095] Quantitation limit stock solution: Accurately measure 2.5 ml of impurity A and bilastine stock solutions, 5 ml of impurity E stock solution and impurity F stock solution, place them in the same 50 ml volumetric flask, dilute to the scale with solvent, and shake well.

[0096] Quantitation limit solution: Take 2 ml of quantitation limit stock solution, place it in a 50 ml volumetric flask, dilute to the mark with solvent, and shake well.

[0097] Quantitative limit solutions of related substances A, impurities B and impurities D: Accurately measure 1 ml of the positioning solutions of related substances A, impurities B and impurities D under the separation test item of Example 3, respectively, place them in a 100 ml volumetric flask, dilute to the mark with solvent, and shake well. Accurately measure 5 ml, place them in a 10 ml volumetric flask, dilute to the mark with solvent, and shake well.

[0098] Impurity C quantitative limit solution: Accurately measure 0.2 ml of impurity C positioning solution, place it in a 100 ml volumetric flask, dilute to the scale with solvent, and shake well.

[0099] Impurity A, impurity E, impurity F and main component detection limit solution: Accurately measure 5 ml of impurity A, impurity E, impurity F and main component quantitative limit solution, place in a 25 ml volumetric flask, dilute to the scale with solvent, and shake well.

[0100] Detection limit solution of related substance A, impurity B and impurity D: Accurately measure 1 ml of the quantitative limit solution of related substance A, impurity B and impurity D, place it in a 10 ml volumetric flask, dilute to the scale with solvent, and shake well.

[0101] Impurity C detection limit solution: Accurately measure 2 ml of impurity C quantitative limit solution, place it in a 10 ml volumetric flask, dilute to the scale with solvent, and shake well.

[0102] Accurately measure 10µl of the above quantitative limit and detection limit solutions, inject them into the liquid chromatograph, and record the chromatogram. The results are shown in Table 2 and Table 3.

[0103] Table 2 Results of quantification limits of related substances

[0104]

[0105] Table 3 Detection limit results of related substances

[0106]

[0107] The results showed that the signal-to-noise ratios of the detection limit solutions of the main component and each known impurity were ≥3; the signal-to-noise ratios of the quantitative limit solutions were all >10, the main component: the quantitative limit was < the reporting limit (0.05%); the quantitative limits of each known impurity were <50% of the limits specified in the quality standard, which met the acceptance criteria, indicating that the method for detecting related substances of bilastine has high sensitivity.

[0108] Example 5 Accuracy Test

[0109] The accuracy of the method was evaluated at three concentration levels within the range of -150% of the limit of quantification.

[0110] Solution preparation:

[0111] Impurity stock solution: Accurately weigh 6.212 mg of impurity A reference substance, 2.653 mg of impurity E reference substance and 2.629 mg of impurity F reference substance, respectively, place them in the same 50 ml volumetric flask, dilute to the scale with solvent, and shake well.

[0112] The quantitative limit stock solution was taken from the quantitative limit and detection limit test in Example 4.

[0113] Quantitative limit recovery solution: Take about 50 mg of bilastine, accurately measure 2 ml of quantitative limit impurity stock solution, place in the same 50 ml volumetric flask, add appropriate amount of solvent, ultrasonically shake for 10 minutes to dissolve the bilastine, cool, dilute to scale with solvent, shake well, filter, and take the filtrate. Prepare 3 copies in parallel.

[0114] 100% recovery solution: Take about 50 mg of bilastine, accurately measure 2 ml of impurity stock solution, place in the same 50 ml volumetric flask, add appropriate amount of solvent, ultrasonically shake for 10 minutes to dissolve the bilastine, cool, dilute to scale with solvent, shake well, filter, and take the filtrate. Prepare 3 copies in parallel.

[0115] 150% recovery solution: Take about 50 mg of bilastine, accurately measure 3 ml of impurity stock solution, place in the same 50 ml volumetric flask, add appropriate amount of solvent, ultrasonically shake for 10 minutes to dissolve the bilastine, cool, dilute to scale with solvent, shake well, filter, and take the filtrate. Prepare 3 copies in parallel.

[0116] Accurately measure 10µl of each of the above recovery solution, reference solution, and test solution, inject them into the liquid chromatograph, and record the chromatogram. The results are shown in Table 4. Figure 6 .

[0117] Table 4 Recovery test results

[0118]

[0119] The results showed that at the quantitative limit concentration, the recoveries of each impurity were in the range of 70% to 130%, and the RSDs were all <20%; at concentrations of 100% and 150%, the recovery of impurity A was in the range of 90% to 110%, and the RSD was <5.0%, and the recoveries of impurities E and F were in the range of 80% to 120%, and the RSD was <10%, which met the acceptance criteria, indicating that the method for detecting related substances of bilastine has high accuracy.

[0120] Example 6 Repeatability Test

[0121] Personnel A shall prepare 6 test sample solutions according to the relevant substance inspection method.

[0122] Accurately measure 10µl of each of the above solutions, inject into the liquid chromatograph, and record the chromatogram. The results are shown in Table 5. Figure 7 .

[0123] Table 5 Relevant substances repeatability test results

[0124]

[0125] The results showed that person A measured the test solution 6 times according to the related substance inspection method, and impurities A, E and F were not detected. The RSD of other maximum single impurities and total impurities was 0.00%<30%, which met the acceptance criteria, indicating that the related substance inspection method of bilastine had good repeatability.

[0126] Example 7 Durability Test

[0127] On the basis of standard chromatographic conditions, different brands of chromatographic columns, column temperatures, and pH values ​​of phosphate buffer in the mobile phase were changed according to the following table. 10 μl of each of the test solution, separation solution, and blank solvent were injected into the liquid chromatograph, and the chromatogram was recorded to examine the durability of the method. The results are shown in Tables 6 to 8.

[0128] Table 6 Robustness of the HPLC method for related substance testing

[0129]

[0130] Table 7 Results of durability test on relevant materials (system suitability)

[0131]

[0132] Note: * indicates standard conditions.

[0133] Table 8 Results of durability test on related substances (impurity detection amount)

[0134]

[0135] Note: * indicates standard conditions.

[0136] The results showed that when three C18 chromatographic columns of different brands were used, the column temperature varied in the range of 30℃±5℃, the pH value of the mobile phase phosphate buffer varied in the range of 6.9±0.2, the separation between impurity E and impurity F in the separation solution was >1.5; in the sensitivity solution chromatogram, the signal-to-noise ratio of the main peak was >10; the blank solvent did not interfere with the detection of related substances of bilastine; in the test solution, the difference in impurity content compared with that under standard conditions was <0.1%, which met the acceptance criteria, indicating that the above chromatographic conditions had good durability.

Claims

1. A method for detecting related substances of bilastine, characterized in that, The method comprises the following steps: taking a separation solution and a test solution for injection respectively, testing according to the conditions of high performance liquid chromatography, and recording a chromatogram; the chromatographic conditions are as follows: a chromatographic column: a chromatographic column with octadecylsilane bonded silica gel as a filler; a mobile phase: a mobile phase A is a phosphate buffer and an organic solvent, and a mobile phase B is an organic solvent, and gradient elution is performed according to the following table: Column temperature: 25-35°C; Wherein, the organic solvent is acetonitrile and methanol, the pH value of the phosphate buffer is 6.6-7.1, and the related substances include the following structure:

2. The method for detecting the related substances of bilastine according to claim 1, wherein The phosphate buffer is selected from one or more of potassium dihydrogen phosphate solution, ammonium dihydrogen phosphate solution, sodium dihydrogen phosphate solution, and calcium dihydrogen phosphate solution.

3. The method for detecting the related substances of bilastine according to claim 2, characterized in that, The concentration of the phosphate is 10-50 mmol / L.

4. The method for detecting the related substances of bilastine according to claim 1, characterized in that The volume ratio of the phosphate buffer to the organic solvent in the mobile phase A is 75-65:25-35.

5. The method for detecting the related substances of bilastine according to claim 1, characterized in that, The volume ratio of the methanol to the acetonitrile is 35-65:65-35.

6. The method for detecting the related substances of bilastine according to claim 1, characterized in that: The separation solution is prepared by the following process: take an appropriate amount of each impurity reference substance, add a solvent to dissolve and dilute, shake well, and use each impurity location solution; take an appropriate amount of bilastine, add a solvent to dissolve it, then add an appropriate amount of each impurity location solution, dilute with a solvent and shake well to obtain; the test solution is prepared by the following process: take an appropriate amount of bilastine, add a solvent to dissolve and dilute and shake well to obtain.

7. The method for detecting the related substances of bilastine according to claim 6, characterized in that: The solvent is acetonitrile and 0.15% phosphoric acid solution, and the volume ratio thereof is 20:

80.

8. Use of the method for detecting related substances of bilastine according to claim 1 in quality control of bilastine.

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