Method for detecting related substances of diclofenac sodium and chlorpheniramine maleate in lofenac sodium and chlorpheniramine maleate tablets
By optimizing gradient elution and specific chromatographic conditions, the problems of insufficient separation and low sensitivity of diclofenac sodium and chlorpheniramine maleate in chlorpheniramine maleate tablets were solved, achieving efficient and reliable quality control and ensuring the safety and consistency of the drug.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2026-03-13
- Publication Date
- 2026-04-10
AI Technical Summary
Existing high-performance liquid chromatography (HPLC) methods for the quality control of chlorpheniramine maleate tablets suffer from problems such as insufficient resolution, low sensitivity, poor reproducibility, and cumbersome operation, making it difficult to meet the requirements of strict quality control and efficient production.
By employing gradient elution conditions and specific chromatographic conditions, using an octadecylsilane-bonded silica column and a trapping column, combined with an ammonium acetate buffer-acetonitrile mobile phase, and detection wavelengths of 254 nm and 225 nm, efficient separation and quantification of diclofenac sodium and chlorpheniramine maleate were achieved.
It achieves complete separation and accurate quantification of all known impurities in compound preparations, improves detection sensitivity and method robustness, reduces run time, and ensures drug safety and quality consistency.
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Abstract
Description
TECHNICAL FIELD
[0001] The present application relates to the field of drug detection, and particularly relates to a method for detecting related substances of diclofenac sodium and chlorphenamine maleate in chlorpheniramine maleate tablets. BACKGROUND
[0002] Chlorpheniramine maleate tablets (commonly known as Ganmaotong tablets) are oral compound preparations composed of 15 mg of diclofenac sodium (a non-steroidal anti-inflammatory drug) and 2.5 mg of chlorphenamine maleate (an antihistamine), which are widely used in clinical practice to relieve symptoms such as fever, headache, and nasal congestion caused by cold. Ensuring the chemical stability of the active ingredients and the impurity level of the preparation to meet the safety standards is the core link of quality control.
[0003] At present, the quality control of the preparation mainly relies on high performance liquid chromatography (HPLC) in the industry and standard institutions. For example, the current Chinese Pharmacopoeia and related national drug standards usually use HPLC-UV method based on reversed-phase chromatography with ultraviolet detector. The general mode of the existing technical solution is to use a C18 chromatographic column, use methanol-water-glacial acetic acid system or acetonitrile-buffer salt system as the mobile phase, use isocratic elution or relatively simple linear gradient program for separation, and detect at a single ultraviolet wavelength.
[0004] However, when such conventional analysis methods are applied to chlorpheniramine maleate tablets, a specific compound preparation, there are several inherent technical defects and limitations, which have been difficult to fully meet the increasingly stringent quality control and efficient production requirements: The elution program used in the existing method is usually simple, and it is difficult to effectively separate all the components to be monitored in the compound preparation within a reasonable analysis time. Diclofenac sodium and chlorphenamine maleate have large differences in chemical properties, and each has a series of known process impurities and degradation products (such as diclofenac sodium impurities A, B, C, F, etc.). These impurities have a wide range of polarities and high similarity in chemical structures. Conventional isocratic or simple gradient elution programs often result in a critical separation degree (such as just meeting the minimum requirement of 1.5 in the pharmacopoeia) between key impurity pairs (such as certain isomers or degradation products of diclofenac sodium), and poor method robustness. When the chromatographic column batch, environmental temperature, or mobile phase preparation fluctuates slightly, peak co-elution often occurs, resulting in serious distortion of the quantitative results of individual impurities, and the impurity spectrum of the product cannot be truly and accurately reflected.
[0005] The detection limit of the existing HPLC-UV method is usually at the level of 0.05% (500 ppm), and trace impurities with a content lower than this level cannot be effectively detected. With the deepening of the awareness of drug safety, international regulatory guidelines (such as ICH M7) require strict control of potential genotoxic impurities, and the allowable limit is often at the ppm or even ppb level. The sensitivity of the existing technology is far from enough to meet the monitoring needs of such high-risk impurities, which constitutes a potential risk to drug safety.
[0006] The existing method is sensitive to slight changes in chromatographic conditions such as mobile phase pH, organic phase ratio, chromatographic column brand and bonded phase density. This leads to problems such as retention time drift and separation degree change when the method is transferred between different laboratories, different instruments or different analysts, making it difficult to guarantee the reproducibility and reliability of the method and increasing the difficulty and cost of implementing quality standards.
[0007] Some existing technical solutions require the establishment of two independent chromatographic systems or the analysis of two or more samples to determine the related substances of the two main components respectively. This method is not only cumbersome, time-consuming and reagent-consuming, but also introduces more system errors, which does not conform to the development trend of modern analytical chemistry which is green, efficient and integrated.
[0008] In summary, there is an urgent need in the art for a related substance detection method that overcomes the above-mentioned shortcomings. SUMMARY
[0009] In view of the above-mentioned shortcomings, the present application provides a method for detecting the related substances of diclofenac sodium and chlorpheniramine maleate in chlorfeniramine maleate tablets.
[0010] The method of the present application detects impurities of diclofenac sodium and chlorpheniramine maleate in chlorfeniramine maleate tablets by high performance liquid chromatography (HPLC), wherein the impurities include diclofenac sodium impurity A, diclofenac sodium impurity B, diclofenac sodium impurity C, diclofenac sodium impurity F, chlorpheniramine maleate impurity B, chlorpheniramine maleate impurity C, and chlorpheniramine maleate impurity 6. The steps of the method of the present application are as follows: (1) Prepare the test solution. Take the test sample, mix it well, accurately weigh an appropriate amount, and place it in a 25ml volumetric flask. Add an appropriate amount of 50% volume fraction acetonitrile, and ultrasonicate for 15 minutes to dissolve the diclofenac sodium and chlorpheniramine maleate. Dilute to the mark with 50% volume fraction acetonitrile, shake well, filter, and take the filtrate.
[0011] (2) Preparation of the control solution, respectively, dichlorophenac sodium control, chlorpheniramine maleate control appropriate amount of the sample, 50% volume fraction of acetonitrile solution and quantitative dilution of each 1 ml containing about 3 μg of dichlorophenac sodium, 1 μg of chlorpheniramine maleate mixed solution.
[0012] (3) Preparation of the system solution, respectively, dichlorophenac sodium, dichlorophenac sodium impurity D, chlorpheniramine maleate and chlorpheniramine maleate impurity C control each appropriate amount, 50% volume fraction of acetonitrile solution and quantitative dilution of each 1 ml containing about 0.6 mg of dichlorophenac sodium, 3 μg of dichlorophenac sodium impurity D, 0.1 mg of chlorpheniramine maleate, 1 μg of chlorpheniramine maleate impurity C mixed solution. In the chromatogram of the system solution, the separation between the dichlorophenac sodium peak and the dichlorophenac sodium impurity D peak (254 nm) should be not less than 1.5, and the ratio of the peak height of the chlorpheniramine maleate impurity C peak to the valley height between the chlorpheniramine maleate and the chlorpheniramine maleate impurity C (225 nm) should be greater than 1.5.
[0013] (4) Precision of the sample solution and the control solution, respectively, inject liquid chromatograph, record the chromatogram.
[0014] The chromatographic conditions are as follows: octadecylsilane bonded silica gel as the filler (Xtimate C18, 4.6x250mm, 5μm or equivalent performance chromatographic column), install the trapping column (Welch Ghost-Buster Column, 4.6mmx50mm or equivalent trapping column) between the pump mixer and the injector; ammonium acetate buffer (take 0.77g ammonium acetate, dissolve in 1000ml water, and adjust the pH to 5.3±0.1 with glacial acetic acid)-acetonitrile (70:30) as the mobile phase A; acetonitrile as the mobile phase B, eluted according to the following table gradient; the flow rate is 1.0ml per minute; the column temperature is 30℃; the detection wavelength is 254nm and 225nm; the sample disc temperature is 10℃; the injection volume is 20μl.
[0015]
[0016] (5) Limit of the determination method, the standard is as follows: if there is an impurity peak in the chromatogram of the sample solution, the related impurities of dichlorophenac sodium (254nm) are calculated by the peak area according to the main component of dichlorophenac sodium plus the correction factor, and each shall not exceed 0.5%; other single impurities (254nm) are calculated by the peak area according to the main component of dichlorophenac sodium, and each shall not exceed 0.5%; (the relative retention time and correction factor of each impurity peak are shown in the table below)
[0017] The relative retention time and correction factor of each impurity peak are shown in the following table.
[0018] The total impurities should not be more than 5.0%.
[0019] The present application has the advantages of: The present application is a method for detecting related substances of chlorpheniramine maleate tablets, which can perform integrated quality control on compound preparations. The method has higher separation efficiency, sensitivity and durability, can ensure complete separation and accurate quantification of all known impurities, and has sufficient detection capability for unknown impurities, thereby providing more reliable technical support for ensuring the safety, effectiveness and quality consistency of the drug.
[0020] Compared with the traditional elution mode in which the mobile phase is completely reduced to 0% and then increased to 100%, the gradient elution condition of the present application can reduce the running time, the mobile phase A can recover the column balance faster after elution, thereby reducing the total running time; and by reducing the concentration of the mobile phase A in stages, different polar compounds can be more effectively separated during the elution process, thereby improving the separation degree. BRIEF DESCRIPTION OF DRAWINGS
[0021] Figure 1 System suitability solution chromatogram (254nm) Figure 2 System suitability solution chromatogram (225nm) Figure 3 Reference solution chromatogram (254nm) Figure 4 Reference solution chromatogram (225nm) Figure 5 Test solution chromatogram (254nm) Figure 6 Test solution chromatogram (225nm) Figure 7 Diclofenac sodium linear relationship diagram Figure 8 Diclofenac sodium impurity linear relationship diagram (impurities include diclofenac sodium impurity A, diclofenac sodium impurity B, diclofenac sodium impurity C, diclofenac sodium impurity D, diclofenac sodium impurity E, and diclofenac sodium impurity F) Figure 9 Chlorpheniramine maleate linear relationship diagram Figure 10Linear relationship diagram of chlorpheniramine maleate impurities (impurities include chlorpheniramine maleate impurity A, chlorpheniramine maleate impurity B, chlorpheniramine maleate impurity C, chlorpheniramine maleate impurity D, chlorpheniramine maleate impurity 6) Detailed Implementation
[0022] Example 1
[0023] Preparation of experimental solutions Test solution: Take 20 tablets of this product (Hubei Renyue, batch number 240108), grind and mix them finely, weigh an appropriate amount (approximately equivalent to 15 mg of diclofenac sodium), accurately weigh it, place it in a 25 ml volumetric flask, add an appropriate amount of 50% acetonitrile, sonicate for 15 minutes to dissolve diclofenac sodium and chlorpheniramine maleate, dilute with 50% acetonitrile to the mark, shake well, filter, and collect the filtrate.
[0024] Reference solution: Take appropriate amounts of diclofenac sodium reference standard (National Institutes for Food and Drug Control, batch number 100334-201803) and chlorpheniramine maleate reference standard (National Institutes for Food and Drug Control, batch number 100047-202008), accurately weigh them, dissolve them in 50% acetonitrile and dilute quantitatively to prepare a mixed solution containing approximately 3 μg of diclofenac sodium and 1 μg of chlorpheniramine maleate per 1 ml.
[0025] System suitability solution: Weigh appropriate amounts of diclofenac sodium (National Institutes for Food and Drug Control, batch number 100334-201803), diclofenac sodium impurity D (National Institutes for Food and Drug Control, batch number 510136-202001), chlorpheniramine maleate (National Institutes for Food and Drug Control, batch number 100047-202008), and chlorpheniramine maleate impurity C (Shanghai Anpu Cuishi Standard Technical Service Co., Ltd., batch number 2574228) reference standards respectively, dissolve them in 50% acetonitrile, and quantitatively dilute to prepare a mixed solution containing approximately 0.6 mg of diclofenac sodium, 3 μg of diclofenac sodium impurity D, 0.1 mg of chlorpheniramine maleate, and 1 μg of chlorpheniramine maleate impurity C per 1 ml.
[0026] Determination methods Chromatographic conditions The system suitability requirements are met when the resolution between the peaks for the sodium diclofenac and sodium diclofenac impurity D (254 nm), and the resolution between the peaks for the chlorpheniramine maleate and chlorpheniramine maleate impurity C (225 nm) are not less than 1.5, and the ratio of the height of the chlorpheniramine maleate impurity C peak to the valley height between the peaks for the chlorpheniramine maleate and chlorpheniramine maleate impurity C (225 nm) is greater than 1.5.
[0027] System suitability requirements The resolution between the peaks for the sodium diclofenac and sodium diclofenac impurity D (254 nm), and the resolution between the peaks for the chlorpheniramine maleate and chlorpheniramine maleate impurity C (225 nm) in the chromatogram of the system suitability solution should be not less than 1.5, and the ratio of the height of the chlorpheniramine maleate impurity C peak to the valley height between the peaks for the chlorpheniramine maleate and chlorpheniramine maleate impurity C (225 nm) should be greater than 1.5.
[0028] As Figure 1 , Figure 2 The resolution between the peaks for the sodium diclofenac and sodium diclofenac impurity D (254 nm), and the resolution between the peaks for the chlorpheniramine maleate and chlorpheniramine maleate impurity C (225 nm) in the chromatogram of the system suitability solution should be not less than 1.5, and the ratio of the height of the chlorpheniramine maleate impurity C peak to the valley height between the peaks for the chlorpheniramine maleate and chlorpheniramine maleate impurity C (225 nm) should be greater than 1.5.
[0029] Determination method The test solution and the reference solution are precisely measured and injected into the liquid chromatograph, and the chromatogram is recorded, as shown in Figures 3 to 6 .
[0030] Limits If there are impurity peaks in the chromatogram of the test solution, the related impurities of sodium diclofenac (254 nm) are calculated by the external standard method with the peak area according to the main component of sodium diclofenac plus a correction factor, and each should not be more than 0.5%; other single impurities (254 nm) are calculated by the external standard method with the peak area according to the main component of sodium diclofenac, and each should not be more than 0.5%; (the relative retention time and correction factor of each impurity peak are shown in Table 2) The related impurities of chlorpheniramine maleate (225 nm) are calculated by the external standard method with the peak area according to the main component of chlorpheniramine maleate plus a correction factor, and each should not be more than 1.0%; (the relative retention time and correction factor of each impurity peak are shown in Table 3) The total impurities should not be more than 5.0%.
[0031] Example 2 Methodology validation Linear relationship investigation Preparation of diclofenac sodium reference solution: precisely take 10 mg of diclofenac sodium reference, diclofenac sodium impurity A reference, diclofenac sodium impurity B reference, diclofenac sodium impurity C reference, diclofenac sodium impurity D reference, diclofenac sodium impurity E reference, and diclofenac sodium impurity F reference, respectively, and place them in 20 ml volumetric flasks. Dissolve and dilute to the calibration mark with 50% volume fraction acetonitrile, shake well, and precisely take 5 ml of each, and place them in the same 50 ml volumetric flask. Dilute to the calibration mark with 50% volume fraction acetonitrile, shake well, and use as the mixed I reference stock solution. Precisely take 0.1, 0.3, 0.5, 0.8, 1, 1.2, and 1.5 ml of the mixed I reference stock solution, respectively, and place them in 10 ml volumetric flasks. Dilute to the calibration mark with 50% volume fraction acetonitrile, shake well, and obtain the mixed I reference ②, ③, ④, ⑤, ⑥, and ⑦ series linear solutions. Precisely take 0.5 ml of the mixed I reference stock solution and place it in a 100 ml volumetric flask. Dilute to the calibration mark with 50% volume fraction acetonitrile, shake well, and obtain the mixed I reference ① linear solution. Preparation of chlorpheniramine maleate reference solution: precisely take 10 mg of chlorpheniramine maleate reference, chlorpheniramine maleate impurity A reference, chlorpheniramine maleate impurity B reference, chlorpheniramine maleate impurity C reference, chlorpheniramine maleate impurity D reference, and chlorpheniramine maleate impurity 6 reference, respectively, and place them in 20 ml volumetric flasks. Dissolve and dilute to the calibration mark with 50% volume fraction acetonitrile, shake well, and precisely take 5 ml of each, and place them in the same 50 ml volumetric flask. Dilute to the calibration mark with 50% volume fraction acetonitrile, shake well, and use as the mixed II reference stock solution. Precisely take 0.1, 0.3, 0.5, 0.8, 1, 1.2, and 1.5 ml of the mixed II reference stock solution, respectively, and place them in 10 ml volumetric flasks. Dilute to the calibration mark with 50% volume fraction acetonitrile, shake well, and obtain the mixed II reference ①, ②, ③, ④, ⑤, ⑥, and ⑦ series linear solutions. Sample injection determination, and the results are shown in Table 4. It shows that each reference has a good linear relationship in the linear range.
[0032] Reference substance information: Diclofenac sodium (batch number 100334-201803, content 100.0%, provided by China Institute for Drug Control); Diclofenac sodium impurity A (batch number 100395-200301, content 100.0%, provided by China Institute for Drug Control); Diclofenac sodium impurity B (batch number 510123-201501, content 100.0%, provided by China Institute for Drug Control); Diclofenac sodium impurity C (batch number 510124-201501, content 100.0%, provided by China Institute for Drug Control); Diclofenac sodium impurity D (batch number 510136-202001, content 100.0%, provided by China Institute for Drug Control); Diclofenac sodium impurity E (batch number 510120-201501, content 100.0%, provided by China Institute for Drug Control); Diclofenac sodium impurity F (batch number 510221-202101, content 100.0%, provided by China Institute for Drug Control); Chlorphenamine maleate (batch number 100047-202008, content 99.7%, provided by China Institute for Drug Control); Chlorphenamine maleate impurity A (batch number 2574188, content 97.1%, provided by Shanghai Anpu Cui Shi Standard Technology Service Co., Ltd.); Chlorphenamine maleate impurity B (2,2'-dipyridylamine, batch number 2574268, content 99.9%, provided by Shanghai Anpu Cui Shi Standard Technology Service Co., Ltd.); Chlorphenamine maleate impurity C (batch number 2574228, content 90.5%, provided by Shanghai Anpu Cui Shi Standard Technology Service Co., Ltd.); Chlorphenamine maleate impurity D (batch number 7-APD-59-4, content 97%, provided by Shanghai Anpu Cui Shi Standard Technology Service Co., Ltd.); Chlorphenamine maleate impurity 6 (batch number STDFZ250523, content 97.3%, provided by China Standard Material Group Co., Ltd.). Reagent information: Acetonitrile (batch number 250526B1, content 99.9%, provided by Xilong Scientific Co., Ltd.); Ammonium acetate (batch number 20230707, content 99.5%, provided by Xiya Reagent Co., Ltd.); Glacial acetic acid (batch number 20250704, content 99.8%, provided by Tianjin Damao Chemical Reagent Factory)
[0033] Sample stability test Take one part of the test sample solution (without standard addition), and sample at 0, 6, 11, 19 and 27 hours for determination. The results are shown in Table 5, indicating that the test sample solution has good stability.
[0034]
[0035] Sampled recovery rate test Preparation of recovery solution: 50 tablets were finely ground and mixed, and an appropriate amount (about equivalent to 15 mg of diclofenac sodium) was accurately weighed into a 25 ml volumetric flask. A total of 18 portions were prepared, 3 of which were accurately added with 0.3 ml of the mixed I control substance stock solution accurately measured in 3.1, and the recovery solution was prepared according to the preparation method of the test solution, which was used as the low concentration recovery solution of the mixed I control substance. 3 of which were accurately added with 1.5 ml of the mixed I control substance stock solution accurately measured in 3.1, and the recovery solution was prepared according to the preparation method of the test solution, which was used as the medium concentration recovery solution of the mixed I control substance. 3 of which were accurately added with 2.4 ml of the mixed I control substance stock solution accurately measured in 3.1, and the recovery solution was prepared according to the preparation method of the test solution, which was used as the high concentration recovery solution of the mixed I control substance. 3 of which were accurately added with 0.75 ml of the mixed II control substance stock solution accurately measured in 3.1, and the recovery solution was prepared according to the preparation method of the test solution, which was used as the low concentration recovery solution of the mixed II control substance. 3 of which were accurately added with 2 ml of the mixed II control substance stock solution accurately measured in 3.1, and the recovery solution was prepared according to the preparation method of the test solution, which was used as the medium concentration recovery solution of the mixed II control substance. 3 of which were accurately added with 3 ml of the mixed II control substance stock solution accurately measured in 3.1, and the recovery solution was prepared according to the preparation method of the test solution, which was used as the high concentration recovery solution of the mixed II control substance. The sample was injected for determination, and the results are shown in Tables 6-7. It is shown that the method has good accuracy for sample determination.
[0036]
[0037]
[0038] Limit of detection and limit of quantification Preparation of diclofenac sodium, chlorpheniramine maleate mixed reference solution: take a certain amount of diclofenac sodium reference substance, diclofenac sodium impurity A reference substance, diclofenac sodium impurity B reference substance, diclofenac sodium impurity C reference substance, diclofenac sodium impurity D reference substance, diclofenac sodium impurity E reference substance, diclofenac sodium impurity F reference substance, chlorpheniramine maleate reference substance, chlorpheniramine maleate impurity B reference substance, chlorpheniramine maleate impurity C reference substance, chlorpheniramine maleate impurity D reference substance, and dissolve and dilute with a certain amount of 50% acetonitrile to prepare a mixed I reference solution with a concentration of 0.125 μg / ml of diclofenac sodium, diclofenac sodium impurity A, diclofenac sodium impurity B, diclofenac sodium impurity C, diclofenac sodium impurity D, diclofenac sodium impurity E, diclofenac sodium impurity F, and diclofenac sodium impurity A; the concentration of chlorpheniramine maleate impurity A is 1.5 μg / ml; the concentration of chlorpheniramine maleate, chlorpheniramine maleate impurity B, chlorpheniramine maleate impurity C, chlorpheniramine maleate impurity D, and chlorpheniramine maleate impurity 6 is 0.5 μg / ml; and the sample is injected for determination. The detection limit and the quantitative limit are calculated according to S / N of 3 and 10, respectively, and the results are shown in Table 8.
[0039]
Claims
1. A method for detecting related substances of diclofenac sodium and chlorpheniramine maleate in chlorpheniramine maleate tablets, characterized in that, The detection method uses high-performance liquid chromatography (HPLC) to detect impurities such as diclofenac sodium and chlorpheniramine maleate in chlorpheniramine maleate tablets. The steps are as follows: (1) Prepare the test solution: take the test sample, grind and mix it, weigh an appropriate amount accurately, place it in a 25 ml volumetric flask, add an appropriate amount of 50% volume fraction acetonitrile, sonicate for 15 minutes to dissolve diclofenac sodium and chlorpheniramine maleate, and dilute to the mark with 50% volume fraction acetonitrile, shake well, filter, and take the filtrate; (2) Prepare reference solutions: Take appropriate amounts of diclofenac sodium reference standard and chlorpheniramine maleate reference standard, weigh them accurately, dissolve them in 50% acetonitrile, and dilute quantitatively to prepare a mixed solution containing approximately 3 μg of diclofenac sodium and 1 μg of chlorpheniramine maleate per ml; (3) Prepare a system suitability solution. Weigh appropriate amounts of diclofenac sodium, diclofenac sodium impurity D, chlorpheniramine maleate, and chlorpheniramine maleate impurity C reference standards, dissolve them in 50% acetonitrile, and dilute quantitatively to prepare a mixed solution containing approximately 0.6 mg of diclofenac sodium, 3 μg of diclofenac sodium impurity D, 0.1 mg of chlorpheniramine maleate, and 1 μg of chlorpheniramine maleate impurity C per 1 ml. In the chromatogram of the system suitability solution, the resolution between the diclofenac sodium peak and the diclofenac sodium impurity D peak at 254 nm should be no less than 1.5, and the ratio of the peak height of chlorpheniramine maleate impurity C at 225 nm to the valley height of chlorpheniramine maleate and chlorpheniramine maleate impurity C should be greater than 1.
5. (4) Accurately measure the test solution and the reference solution, inject them into the liquid chromatograph, and record the chromatograms.
2. The method for detecting related substances of diclofenac sodium and chlorpheniramine maleate in chlorpheniramine maleate tablets as described in claim 1, characterized in that, The chromatographic conditions are as follows: (1) Using octadecylsilane-bonded silica gel as a filler, a trap column is installed between the pump mixer and the injector; (2) Using ammonium acetate buffer-acetonitrile and water mixed solution as mobile phase A, the ammonium acetate buffer is prepared by taking 0.77g of ammonium acetate, adding 1000ml of water to dissolve it, and adjusting the pH to 5.3±0.1 with glacial acetic acid, the volume ratio of the acetonitrile and water mixed solution is 70:30; using acetonitrile as mobile phase B; (3) The gradient elution conditions are as follows: from 0 to 15 min, mobile phase A is 100% and mobile phase B is 0%; from 15 to 40 min, mobile phase A is 71% and mobile phase B is 29%; from 40 to 60.1 min, mobile phase A is 7% and mobile phase B is 93%. During the 60.1~70 min period, mobile phase A was 100% and mobile phase B was 0%. (4) The flow rate is 1.0 ml per minute; the column temperature is 30℃; the detection wavelengths are 254 nm and 225 nm; the sample tray temperature is 10℃; and the injection volume is 20 μl.
3. The method for detecting related substances of diclofenac sodium and chlorpheniramine maleate in chlorpheniramine maleate tablets as described in claim 1, characterized in that, The impurities include diclofenac sodium impurity A, diclofenac sodium impurity B, diclofenac sodium impurity C, diclofenac sodium impurity F, chlorpheniramine maleate impurity B, chlorpheniramine maleate impurity C, and chlorpheniramine maleate impurity 6.
4. A method for detecting related substances of diclofenac sodium and chlorpheniramine maleate in chlorpheniramine maleate tablets according to any one of claims 1 to 3, characterized in that, The relative retention times and correction factors for impurity peaks A, B, C, and F of diclofenac sodium are 1.4 and 0.6, 1.8 and 0.5, 1.5 and 0.9, and 1.6 and 0.3, respectively; the relative retention times and correction factors for impurity peaks B, C, and 6 of chlorpheniramine maleate are as follows: 0.6 and 1.1, 0.9 and 0.7, 0.7 and 1.0.