Method for detecting related impurities in dextromethorphan hydrobromide quinidine sulfate capsule

Abstract

The invention provides a method for detecting the content of dextromethorphan hydrobromide and quinidine sulfate capsules, and provides a convenient, efficient and accurate detection method for solving the problem of detecting the impurity content of the dextromethorphan hydrobromide and quinidine sulfate capsules. The method can be used for detecting the contents of six main impurities in the dextromethorphan hydrobromide and quinidine sulfate capsule: impurity A, impurity B, impurity C, impurity D, hydroquinidine and cinchonine, so that the medication safety is effectively guaranteed, the quality control of the dextromethorphan hydrobromide and quinidine sulfate capsule is facilitated, and the method is convenient, efficient, accurate and suitable for industrial production. The method completely accords with the guidance principle verified by a Chinese pharmacopoeia method in the aspects of system applicability, detection limit, quantitation limit and linearity, and can be used for quality control of dextromethorphan hydrobromide quinidine sulfate capsules.

Description

Technical Field

[0001] The invention belongs to the technical field of drug analysis, and particularly relates to a method for detecting relevant impurities in dextromethorphan hydrobromide and quinidine sulfate capsules. Background Art

[0002] In 2010, the FDA approved the marketing of dextromethorphan hydrobromide quinidine sulfate capsules (trade name: NUEDEXTA), produced by Avanir Pharmaceuticals, Inc. in the United States. The dextromethorphan hydrobromide in the compound capsule preparation is a sigma-1 receptor agonist and a non-competitive NMDA receptor antagonist. Quinidine competitively inhibits cytochrome P450 2D6, reducing the biotransformation of dextromethorphan, thereby increasing the plasma level of dextromethorphan. NUEDEXTA is used to treat pseudobulbar affect (PBA), also known as emotional incontinence, which is mainly secondary to brain damage or neurological diseases such as multiple sclerosis, amyotrophic lateral sclerosis and stroke, and is characterized by sudden unconscious crying or laughing.

[0003] The impurities and structures in dextromethorphan hydrobromide are as follows: Impurity A, chemical name: 3-methoxymorphine enantiomer, structural formula: , Impurity B, Chemical name: 17-methylmorphinan-3-ol enantiomer, Structural formula: , Impurity C, Chemical name: 3-methoxy-17-methylmorphinan-10-one enantiomer, Structural formula: , Impurity D, Chemical name: Dextromethorphan N-oxide, Structural formula: , impurity hydroquinidine, chemical name: (9S)-6′-methoxy-deoxycinchonine-9-ol, structural formula: , impurity cinchona, chemical name: (9S)-cinchona-9-ol, structural formula: The study of impurities is helpful for optimizing the synthesis process and quality control of drugs. The study of impurities in dextromethorphan hydrobromide provides a basis for evaluating the quality of dextromethorphan hydrobromide and its synthetic intermediates, and also provides a technical basis for optimizing the synthesis process of dextromethorphan hydrobromide. It is of great significance to determine the adverse reactions caused by related substances of dextromethorphan hydrobromide.

[0004] CN113720944 discloses a method for detecting the content of dextromethorphan quinidine in dextromethorphan hydrobromide and quinidine sulfate capsules. The method uses a chromatographic column with octadecylsilane bonded silica gel as a filler, an acetonitrile:buffer (aqueous solution of phosphoric acid and triethylamine) system as mobile phase A, acetonitrile as mobile phase B, and a gradient elution. The method does not detect related substances other than dextromethorphan quinidine in dextromethorphan hydrobromide and quinidine sulfate capsules.

[0005] CN117783322 discloses an HPLC analysis method for a dextromethorphan-quinidine composition. The method uses a reverse phase chromatographic column with octadecylsilane bonded silica gel as a filler, 0.05 mol / L potassium dihydrogen phosphate-0.03 mol / L ammonium acetate buffer as mobile phase A, acetonitrile:methanol=1:1 (V / V) as mobile phase B, and gradient elution. The method does not detect hydroquinidine in dextromethorphan hydrobromide and quinidine sulfate capsules.

[0006] CN114324642 ​​discloses a method for determining related substances of dextromethorphan hydrobromide. The method uses an ion exchange chromatography system for analysis, 0.1M ammonium phosphate solution (pH 6.5)-acetonitrile (55:45) (V / V) as the mobile phase, and isocratic elution. The method does not detect hydroquinidine and cinchonine in dextromethorphan hydrobromide quinidine sulfate capsules.

[0007] In summary, the prior art has not disclosed a method for detecting the impurity hydroquinidine in dextromethorphan hydrobromide. In order to fill this technical gap and solve the problem of detecting the impurity content of dextromethorphan hydrobromide quinidine sulfate capsules, the present invention provides a convenient, efficient and accurate detection method, which can simultaneously detect the contents of the impurities hydroquinidine, cinchonine, and other four impurities A, B, C, and D in dextromethorphan hydrobromide, thereby effectively ensuring the safety of medication and facilitating the quality control of dextromethorphan hydrobromide quinidine sulfate capsules. Summary of the invention

[0008] The invention provides a method for detecting the content of dextromethorphan hydrobromide and quinidine sulfate capsules. In order to solve the problem of detecting the impurity content of the dextromethorphan hydrobromide and quinidine sulfate capsules, a convenient, efficient and accurate detection method is provided. The method can detect the contents of six main impurities in the dextromethorphan hydrobromide and quinidine sulfate capsules, thereby effectively ensuring the safety of medication and facilitating the quality control of the dextromethorphan hydrobromide and quinidine sulfate capsules. The method is convenient, efficient and accurate, and fully complies with the guiding principles of method verification of the Chinese Pharmacopoeia in terms of system applicability, detection limit, quantitative limit and linearity, and can be used for the quality control of the dextromethorphan hydrobromide and quinidine sulfate capsules.

[0009] To achieve the above object, the present invention provides the following technical solutions: A method for detecting relevant impurities in dextromethorphan hydrobromide and quinidine sulfate capsules, the detection method comprising the following steps: (1) Prepare solutions, including blank solution, reference solution and test solution; (2) Determination method: The content of dextromethorphan hydrobromide and quinidine sulfate capsules was determined by high performance liquid chromatography. After the system was stable, blank solution, reference solution and test solution were added respectively, and the chromatogram was recorded. Chromatographic conditions are as follows: chromatographic column: octadecylsilane bonded silica gel as filler, detection wavelength: 235nm-280nm; injection volume: 10-20µl; column temperature: 20±2°C; flow rate: 1.0±0.1ml / min; mobile phase A: 30mM potassium hexafluorophosphate + 0.1% phosphate buffer; preparation of the buffer: weigh 5.5g potassium hexafluorophosphate, measure 1ml phosphoric acid, dissolve and dilute to 1000ml with purified water, and mix well; mobile phase B: acetonitrile, gradient elution; The blank solution is mobile phase A: acetonitrile = (62:38, V / V), the mobile phase is: mobile phase A: 30mM potassium hexafluorophosphate + 0.1% phosphate buffer (weigh 5.5g potassium hexafluorophosphate, measure 1ml phosphoric acid, dissolve and dilute to 1000ml with purified water, mix well), mobile phase B: acetonitrile, the test solution: take an appropriate amount of dextromethorphan hydrobromide, place it in a volumetric flask, add blank solution to ultrasonically dissolve and dilute to the scale, shake well, the reference solution: take an appropriate amount of impurity A reference, impurity B reference, impurity C reference, impurity D reference, hydroquinidine reference, cinchonine reference, dextromethorphan hydrobromide reference, quinidine sulfate reference and place them in the same volumetric flask, add an appropriate amount of blank solution to dissolve and dilute to the scale, shake well, and the chromatographic column is Horizon C18 / AR, 4.6*250mm, 5µm.

[0010] The mobile phase gradient process is shown in Table 1 below:

[0011] The contents of impurities hydroquinidine, cinchonine, impurities A, B, C, and D in the test sample dextromethorphan hydrobromide and quinidine sulfate capsules were calculated according to the following formula:

[0012] Among them: A S : Peak area of ​​known impurities in the test solution; C R : The content of impurities in the reference solution; M R : Sampling amount of impurities in reference solution (unit: mg); N S : dilution factor of the test solution; W: average particle weight (unit: mg); A R : peak area of ​​impurity reference solution; M S : The sampling amount of the test product (unit: mg); N R : Dilution multiple of impurity reference solution; Q: Specification of test sample (mg).

[0013] The detection method has been verified by methodology and meets relevant requirements. The test results are shown in Table 2 below:

[0014] In order to solve the problem of detecting relevant impurities in dextromethorphan hydrobromide and quinidine sulfate capsules, this invention provides a convenient, efficient and accurate detection method, which can be used for the quality control of dextromethorphan hydrobromide and quinidine sulfate capsules. This method adopts high performance liquid chromatography for analysis, fills the gap in the prior art, and solves the problem of detecting the main relevant impurities in dextromethorphan hydrobromide. A convenient, efficient and accurate detection method is provided. This method can detect the contents of the main 6 impurities in dextromethorphan hydrobromide, which is convenient for the quality control of dextromethorphan hydrobromide and quinidine sulfate capsules. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] Figure 1 Spectrum of dextromethorphan hydrobromide localization solution in Example 1; Figure 2 Spectrum of quinidine sulfate localization solution in Example 1; Figure 3 Typical spectra of the reference solution in Example 2; Figure 4 LOD solution spectrum in Example 3; Figure 5 LOQ-1 solution spectrum in Example 3; Figure 6 Typical spectrum of linear solution -100% in Example 3; Figure 7 Linear relationship diagram of impurity A in Example 3; Figure 8 Linear relationship diagram of impurity B in Example 3; Fig. 9 Linear relationship diagram of impurity C in Example 3; Fig.10 Linear relationship diagram of impurity D in Example 3; Fig.11 Linear relationship diagram of impurity cinchonis in Example 3; Fig.12 Linear relationship diagram of impurity hydroquinidine in Example 3; Fig.13 Comparative example spectrum. DETAILED DESCRIPTION

[0016] The present invention is further illustrated by specific examples. It should be understood that the examples of the present invention are only used to illustrate the present invention, rather than to limit the present invention. The technical solutions obtained by simply improving the present invention or by equivalently replacing conventional means or components on the basis of the technical solution of the present invention all belong to the protection scope of the present invention. The information of the instruments, chromatographic columns, reagents, reference substances, test substances, etc. used in the embodiments of the present invention are shown in Tables 3, 4, and 5.

[0017]

[0018]

[0019]

[0020] Example 1 Detection method (1) Detection conditions and reagents Instrument: Ultra-high performance liquid chromatograph: model: Agilent 1260+Dionex U3000, chromatographic column: Horizon C18 / AR, 4.6*250 mm, 5 um, detection wavelength: 280 nm, injection volume: 20 µl, column temperature: 20 °C, flow rate: 1.0 ml / min, electronic analytical balance, gradient elution conditions are shown in Table 1.

[0021] Reagents and reference substances: acetonitrile: HPLC; phosphoric acid: AR; potassium hexafluorophosphate: AR; water: ultrapure water; dextromethorphan hydrobromide: content 94.8%; quinidine sulfate: NA; impurity A: content 99.7%; impurity B: content 98.7%; impurity C: content 99.8%; impurity D: 99.9%; hydroquinidine: 95.0%; cinchonine: 98.0%.

[0022] (2) Test operation Solution preparation: Blank solution / diluent: mobile phase A: acetonitrile = (62:38); Impurity A stock solution: take 7.5 mg of impurity A, accurately weigh, place in a 50 ml volumetric flask, dissolve and dilute to the mark with acetonitrile, and shake well; Impurity B stock solution: take 7.5 mg of impurity B, accurately weigh, place in a 50 ml volumetric flask, dissolve and dilute to the mark with acetonitrile, and shake well; Impurity C stock solution: take 7.5 mg of impurity C, accurately weigh, place in a 50 ml volumetric flask, dissolve and dilute to the mark with acetonitrile, and shake well; Impurity D stock solution: take 7.5 mg of impurity D, accurately weigh, place in a 50 ml volumetric flask, dissolve and dilute to the mark with acetonitrile, and shake well; Hydroquinidine stock solution: Take 75 mg of dihydroquinidine reference substance, accurately weigh it, put it into a 25 ml volumetric flask, dissolve it in acetonitrile and dilute it to the mark, shake well; Cinchonine stock solution: Take 5 mg of Cinchonine reference substance, weigh accurately, place in a 250 ml volumetric flask, dissolve and dilute to scale with acetonitrile, and shake well; Dextromethorphan hydrobromide fixative solution: weigh 25 mg of dextromethorphan hydrobromide reference substance, place in a 25 ml volumetric flask, add 3 ml of purified water to dissolve by ultrasonication, dilute to scale with acetonitrile, and shake well; Quinidine sulfate fixative solution: weigh 25 mg of quinidine sulfate reference substance, place in a 25 ml volumetric flask, add 3 ml of purified water and sonicate to dissolve, dilute to scale with acetonitrile, and shake well; Impurity A positioning solution: Pipette 1 ml of impurity A stock solution into a 10 ml volumetric flask, dilute to the mark with diluent, and shake well; Impurity B positioning solution: Pipette 1 ml of the impurity B stock solution into a 10 ml volumetric flask, dilute to the mark with diluent, and shake well; Impurity C positioning solution: Pipette 1 ml of the impurity C stock solution into a 10 ml volumetric flask, dilute to the mark with diluent, and shake well; Impurity D positioning solution: Pipette 1 ml of the impurity D stock solution into a 10 ml volumetric flask, dilute to the mark with diluent, and shake well; Hydroquinidine positioning solution: Pipette 1 ml of the hydroquinidine stock solution into a 10 ml volumetric flask, dilute to the mark with diluent, and shake well; Cinchonine positioning solution: Pipette 1 ml of Cinchonine stock solution into a 10 ml volumetric flask, dilute to scale with diluent, and shake well; Dextromethorphan hydrobromide positioning solution: Pipette 1 ml of dextromethorphan hydrobromide stock solution into a 10 ml volumetric flask, dilute to the mark with diluent, and shake well; Quinidine sulfate fixative solution: Pipette 1 ml of quinidine sulfate stock solution into a 10 ml volumetric flask, dilute to scale with diluent, and shake well; SST (10): Pipette 1 ml of each stock solution into a 10 ml volumetric flask, dilute to scale with diluent, and shake well; SST (100): Pipette 1 ml of each stock solution into the same 10 ml volumetric flask, dilute to the mark with acetonitrile, and shake well. Pipette 1 ml of the above solution into a 10 ml volumetric flask, dilute to the mark with diluent, and shake well; Sampling and data processing: After the system is stable, inject 1 injection of blank solution, 1 injection of SST (10), 1 injection of SST (100), and 1 injection of each positioning solution, and record the chromatogram; The content of each known impurity in Dextromethorphan Hydrobromide and Quinidine Sulfate Capsules is calculated according to the following formula:

[0023] Among them: A S: Peak area of ​​known impurities in the test solution; C R : The content of impurities in the reference solution; M R : Sampling amount of impurities in reference solution (unit: mg); N S : dilution factor of the test solution; W: average particle weight (unit: mg); A R : peak area of ​​impurity reference solution; M S : The sampling amount of the test product (unit: mg); N R : Dilution multiple of impurity reference solution; Q: Specification of test sample (mg).

[0024] Example 2 System Applicability System suitability is achieved by evaluating the signal-to-noise ratio (S / N) of each impurity in the sensitivity solution and the RSD of the peak area of ​​each impurity in the 6-point reference solution. It is required that the signal-to-noise ratio (S / N) of each impurity in the sensitivity solution should be no less than 10; the RSD of the peak area of ​​each impurity in the 6-point reference solution should be no more than 10.0%.

[0025] Solution preparation: Preparation of sensitivity solution: pipette 1 ml of each stock solution into the same 10 ml volumetric flask, dilute to the mark with diluent, and shake well; Preparation of reference solution: take appropriate amount of impurity A reference, impurity B reference, impurity C reference, impurity D reference, hydroquinidine reference, cinchonine reference, dextromethorphan hydrobromide reference, and quinidine sulfate reference into the same volumetric flask, add appropriate amount of blank solution to dissolve and dilute to the mark, and shake well; Injection: After the system is stable, inject 1 injection of the sensitive solution and 6 injections of the reference solution, and perform the injection measurement according to the detection method of Example 1 and the chromatographic conditions in Example 1, and record the chromatogram. The test shows that the blank solution has no interference with the detection; the impurities of dextromethorphan hydrobromide can be effectively separated, and the separation degree is greater than 1.5, which meets the requirements. The relative retention time is shown in Table 6:

[0026] Example 3 Detection limit, quantitation limit and linearity test The detection limit is obtained by detecting that the ratio of its response signal to noise is not less than 3:1; the quantification limit is obtained by detecting that the ratio of its response signal to noise is not less than 10:1. At the LOQ concentration level, 6 quantification limit test solutions are repeatedly examined, and the RSD of the peak area per unit concentration of each impurity in the 6 LOQ solutions should be no more than 20.0%; each LOQ impurity should be no more than 1.02ppm, and the signal-to-noise ratio (S / N) of each impurity in the LOQ solution should be ≥10; the signal-to-noise ratio (S / N) of each impurity in the LOD solution should be ≥3, and LOD < LOQ.

[0027] Six points were evenly selected within the range of LOQ concentration to 150% limit concentration, and the concentration was used as the horizontal axis and the peak area as the vertical axis to draw a curve. It is required that each impurity should be linear within the range of LOQ concentration to 150% limit concentration, and the square of the correlation coefficient R (R 2 ) should be no less than 0.99, and the absolute value of the y-intercept should be within 25% of the 100% concentration peak area.

[0028] Solution preparation: Dextromethorphan hydrobromide mixed standard stock solution: Weigh 25 mg of impurities A, B, C, and D respectively, accurately weigh them, place them in the same 50 ml volumetric flask, add 3 ml of purified water to dissolve them by ultrasonication, dilute to the scale with acetonitrile, shake well, and obtain; Cinchonine stock solution: Weigh 25 mg of Cinchonine accurately, place in a 50 ml volumetric flask, add 3 ml of purified water, sonicate to dissolve, dilute to scale with acetonitrile, shake well, and obtain; Hydroquinidine stock solution: Weigh 375 mg of hydroquinidine accurately, place in a 50 ml volumetric flask, add 3 ml of purified water to dilute and dissolve, and dilute to the mark with acetonitrile; LOQ dextromethorphan hydrobromide mixed standard stock solution: accurately measure 4 ml of dextromethorphan hydrobromide mixed standard stock solution into a 20 ml volumetric flask, dilute to the mark with diluent, and shake well; LOQ hydroquinidine stock solution: Accurately measure 1 ml of hydroquinidine stock solution and place it in a 150 ml volumetric flask, dilute to the mark with diluent, and shake well; LOQ solution: Accurately measure 1 ml of LOQ dextromethorphan hydrobromide mixed standard stock solution, LOQ hydroquinidine stock solution, and cinchonine stock solution and place them in the same 100 ml volumetric flask, dilute to the scale with diluent, and shake well; LOD solution: accurately measure 3 ml of LOQ solution and place it in a 10 ml volumetric flask, dilute to the mark with diluent, and shake well; 100% Cinchonine stock solution: Accurately measure 2 ml of Cinchonine stock solution and place it in a 20 ml volumetric flask, dilute to the mark with diluent, and shake well; 100% linear solution: accurately measure 1 ml of dextromethorphan hydrobromide mixed standard stock solution, hydroquinidine stock solution, and 100% cinchonaline stock solution and place them in the same 50 ml volumetric flask, dilute to the scale with diluent, and shake well; 50% linear solution: accurately measure 5 ml of 100% linear solution and place it in a 10 ml volumetric flask, dilute to the mark with diluent, and shake well; 20% linear solution: accurately measure 2 ml of 100% linear solution and place it in a 10 ml volumetric flask, dilute to the mark with diluent, and shake well; 150% linear solution: accurately measure 3 ml of dextromethorphan hydrobromide mixed standard stock solution, 3 ml of hydroquinidine stock solution, and 1 ml of cinchonine stock solution and place them in the same 100 ml volumetric flask, dilute to the scale with diluent, and shake well; Injection: After the system is stable, inject 1 injection of blank solution, 1 injection of LOD solution, 6 injections of LOQ solution, and 1 injection of each linear solution, and record the chromatogram. The conversion results according to the formula are shown in Table 7-Table 14 below:

[0029]

[0030]

[0031]

[0032]

[0033]

[0034]

[0035] .

[0036] Comparative Example (1) Detection conditions and reagents Instrument: High performance liquid chromatograph: model: Agilent 1260, chromatographic column: Xbridge ShieldRP 18 4.6*150mm, 5μm, detection wavelength: 280nm, injection volume: 10μl, column temperature: 30℃, flow rate: 0.6ml / min, mobile phase A: ultrapure water, mobile phase B: acetonitrile, mobile phase C: pH6.5 0.1mol / L diammonium dihydrogen phosphate solution, electronic analytical balance, gradient elution conditions are shown in Table 15 below.

[0037]

[0038] Reagents and reference substances: acetonitrile: HPLC; diammonium phosphate: GR; dextromethorphan hydrobromide: content 94.8%; quinidine sulfate: NA; impurity A: content 99.7%; impurity B: content 98.7%; impurity C: content 99.8%; impurity D: 99.9%; hydroquinidine: content 95.0%; cinchonine: content 98.0%.

[0039] (2) Test operation Solution preparation: Impurity A stock solution: Take 7.5 mg of impurity A, accurately weigh it, put it in a 50 ml volumetric flask, dissolve it in acetonitrile and dilute it to the mark, shake well; Impurity B stock solution: Take 7.5 mg of impurity B, accurately weigh it, put it in a 50 ml volumetric flask, dissolve it in acetonitrile and dilute it to the mark, shake well; Impurity C stock solution: Take 7.5 mg of impurity C, accurately weigh it, put it in a 50 ml volumetric flask, dissolve it in acetonitrile and dilute it to the mark, shake well; Impurity D stock solution: Take 7.5 mg of impurity D, accurately weigh it, put it in a 50 ml volumetric flask, dissolve it in acetonitrile and dilute it to the mark, shake well; Hydroquinidine stock solution: Take 75 mg of hydroquinidine reference substance, accurately weigh it, put it into a 25 ml volumetric flask, dissolve it in acetonitrile and dilute it to the mark, shake well; Cinchonine stock solution: Take 5 mg of Cinchonine reference substance, weigh accurately, place in a 250 ml volumetric flask, dissolve and dilute to scale with acetonitrile, and shake well; System suitability solution: Take about 30 mg of dextromethorphan hydrobromide reference substance and about 20 mg of quinidine sulfate reference substance, accurately weigh them, place them in the same 20 ml volumetric flask, dissolve them in acetonitrile, measure 1 ml of impurity A stock solution, impurity B stock solution, impurity C stock solution, impurity D stock solution, hydroquinidine stock solution, and cinchonine stock solution respectively, place them in the same 20 ml volumetric flask, dilute to the scale with acetonitrile, shake well, filter, and take the filtrate to obtain.

[0040] Sampling and data processing: After the system is stable, inject one injection of system suitability solution and record the chromatogram.

[0041] Result analysis: According to the attached Fig.13 It can be seen that the chromatogram obtained by the detection method of this comparative example showed obvious double peaks and tailing, indicating that the stationary phase and mobile phase selection of this detection method are not applicable, and ghost peaks that should not exist appear, and some impurity peaks cannot be detected. It can be seen that the use of ammonium dihydrogen phosphate solution and acetonitrile as mobile phases to detect the contents of the six main impurities in dextromethorphan hydrobromide is not applicable.

Claims

1. A method for detecting relevant impurities in dextromethorphan hydrobromide and quinidine sulfate capsules, characterized in that: The steps include: (1) Prepare solutions, including blank solution, reference solution and test solution; (2) Determination method: Use high performance liquid chromatography to determine the content of relevant impurities in dextromethorphan hydrobromide and quinidine sulfate capsules. After the system is stable, add blank solution, reference solution and test solution respectively, and record the chromatogram; Chromatographic conditions are as follows: chromatographic column: octadecylsilane bonded silica gel as filler, detection wavelength: 235nm-280nm; injection volume: 10-20µl; column temperature: 20±2°C; flow rate: 1.0±0.1ml / min; mobile phase A: 30mM potassium hexafluorophosphate + 0.1% phosphate buffer; preparation of the buffer: weigh 5.5g potassium hexafluorophosphate, measure 1ml phosphoric acid, dissolve and dilute to 1000ml with purified water, and mix well; mobile phase B: acetonitrile, gradient elution, the mobile phase gradient process is as follows: 。 2. The method for detecting relevant impurities in dextromethorphan hydrobromide and quinidine sulfate capsules according to claim 1, characterized in that: The chromatographic column is Horizon C18 / AR, 4.6*250mm, 5µm.

3. The method for detecting impurities in a dextromethorphan hydrobromide and quinidine sulfate capsule according to any one of claims 1 to 2, characterized in that: The relevant impurities are the following impurities A, B, C and D and hydroquinidine Cinchonine .

4. The detection method according to claim 3, characterized in that: The blank solution is a mobile phase A: acetonitrile with a volume ratio of 62:38; the test solution: take an appropriate amount of dextromethorphan hydrobromide, place it in a volumetric flask, add the blank solution to ultrasonically dissolve and dilute to the scale, and shake well; the reference solution: take an appropriate amount of impurity A reference, impurity B reference, impurity C reference, impurity D reference, hydroquinidine reference, cinchonine reference, dextromethorphan hydrobromide reference, and quinidine sulfate reference in the same volumetric flask, add an appropriate amount of blank solution to dissolve and dilute to the scale, and shake well.

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