Method for determining impurities in desloratadine oral solution

Abstract

The invention discloses a method for determining impurities in a desloratadine oral solution, the impurities comprise a desloratadine impurity 1, the determination method adopts a high performance liquid chromatography, and the detection conditions of the high performance liquid chromatography are as follows: a chromatographic column is an octyl silane bonded silica gel column or an efficiency equivalent column; the detection wavelength is 254 + / -2nm; the detector is an ultraviolet detector; the column temperature is 35-45 DEG C; the flow rate is 1.1 to 1.3 mL / min; mobile phases: a dipotassium phosphate buffer solution, methanol and acetonitrile; the elution mode is isocratic elution. The determination method disclosed by the invention is good in specificity, good in separation degree, high in sensitivity and good in accuracy, can fully meet the requirements of impurity determination, has important meanings for evaluating the quality of raw material medicines and the advantages and disadvantages of a preparation process, controlling the quality of a final product and detecting a stable sample, and is high in practicability in actual quality control work.

Description

Technical Field

[0001] The invention relates to the technical field of medical detection, and in particular to a method for determining impurities in a desloratadine oral solution. Background Art

[0002] The chemical name of desloratadine is 8-chloro-6,11-dihydro-11(4-piperidinyl)-5H-benzo-[5,6]heptane[1,2-b]pyridine. It is a non-sedating long-acting tricyclic antihistamine and an active metabolite of loratadine. It can relieve the symptoms of allergic rhinitis or chronic idiopathic urticaria by selectively antagonizing peripheral H1 receptors. Its structure is as follows:

[0003]

[0004] Currently, the desloratadine preparations approved for marketing are mainly divided into two categories: solid dosage forms and liquid dosage forms. Among them, desloratadine oral solution is a product suitable for children of different ages. It can be used for targeted anti-allergic treatment of children. It has a good taste, is easy to swallow, has an accurate oral dose, and is easily accepted by children. However, desloratadine oral solution may produce impurities during the production and storage process, causing adverse reactions in clinical use and affecting the safety of clinical medication. Therefore, it is necessary to develop specific related substance analysis methods to control impurities.

[0005] The synthesis of desloratadine raw materials is mainly prepared by hydrolysis synthesis of loratadine. However, due to the many synthetic routes of loratadine, the quality is uneven, which also affects the related substances of desloratadine oral solution. One of the impurities is 8-chloro-11-(1-methylpiperidin-4-ylidene)-6,11-dihydro-5H-benzo[5,6]cycloheptyl[1,2-b]pyridine (also known as desloratadine impurity 1), and its molecular formula is C 20 H 21 C1N 2 , molecular weight 324.85, CAS number 38092-89-6, which is very close to desloratadine (molecular weight 310.82) in structure and polarity, which means that the two are difficult to separate when tested by HPLC. In addition, the methods for analyzing and determining the impurity in desloratadine oral solution are not recorded in the pharmacopoeia standards and literature of various countries. The chemical structure of desloratadine impurity 1 is as follows:

[0006]

[0007] Therefore, there is an urgent need to develop an analytical method that can effectively detect desloratadine impurity 1 in desloratadine oral solution. Summary of the invention

[0008] The present invention aims to provide a method for determining impurities in a desloratadine oral solution. The method can effectively separate desloratadine from impurities with similar polarity and difficult to separate, and can eliminate the interference caused by a blank solvent and an auxiliary material solution. The method can be used for detecting related substances in the preparation process, finished product and storage process of the desloratadine oral solution, thereby reducing the risk of clinical use.

[0009] The impurities targeted by the present invention include 8-chloro-11-(1-methylpiperidin-4-ylidene)-6,11-dihydro-5H-benzo[5,6]cycloheptyl[1,2-b]pyridine, whose CAS number is 38092-89-6, also known as desloratadine impurity 1.

[0010] According to one aspect of the present invention, a method for determining impurities in a desloratadine oral solution is provided, wherein the impurities include 8-chloro-11-(1-methylpiperidin-4-ylidene)-6,11-dihydro-5H-benzo[5,6]cycloheptyl[1,2-b]pyridine (i.e., desloratadine impurity 1), and the method for determining the impurities uses high performance liquid chromatography, wherein the detection conditions of the high performance liquid chromatography include:

[0011] Chromatographic column: octylsilane bonded silica gel column or column with equivalent performance;

[0012] Detection wavelength: 254±2nm;

[0013] Detector: UV detector;

[0014] Column temperature: 35-45°C;

[0015] Flow rate: 1.1-1.3 mL / min;

[0016] Mobile phase: potassium hydrogen phosphate buffer, methanol and acetonitrile;

[0017] Elution mode: isocratic elution.

[0018] The present invention can effectively separate desloratadine and desloratadine impurity 1 by using high performance liquid chromatography to determine desloratadine oral solution, and the detection time is short, thereby saving detection cost and improving detection efficiency. In addition, the method of the present invention has good specificity, good separation, high sensitivity and good accuracy, can fully meet the requirements of the above-mentioned impurity determination, is of great significance for evaluating the quality of raw materials and the quality of preparation processes, final product quality control and stability sample detection, and has strong practicality in actual quality control work.

[0019] In some embodiments, the pH of the potassium phosphate buffer is 7.1-7.3.

[0020] In some embodiments, the preparation method of dipotassium hydrogen phosphate buffer is as follows: take 1.57g-1.92g of dipotassium hydrogen phosphate, add 1L of water to dissolve it, add 2.7ml-3.3ml of triethylamine and stir to mix, adjust the pH to 7.1-7.3 with phosphoric acid, filter, and ultrasonicate to obtain.

[0021] In some embodiments, the volume ratio of potassium hydrogen phosphate buffer, methanol and acetonitrile is 50:25:25.

[0022] In some embodiments, the octylsilane bonded silica gel column used is a Symmetry C8 chromatographic column with a length of 150 mm, an inner diameter of 4.6 mm, and a filler particle size of 5 μm.

[0023] In some embodiments, the detection wavelength is 254 nm, the column temperature is 40° C., and the flow rate is 1.2 mL / min.

[0024] In some embodiments, the injection volume for HPLC is 20-100 μL.

[0025] In some embodiments, the assay method further comprises preparing a reference solution, and the preparation of the reference solution comprises the following steps:

[0026] S1. Take the impurity reference substance, weigh it accurately, dissolve it with a diluent and dilute it as the reference substance reserve intermediate solution;

[0027] S2. Accurately measure the reference substance reserve intermediate solution and dilute it with a diluent to obtain the reference substance reserve solution;

[0028] S3. Accurately measure the reference substance stock solution and dilute it with a diluent to obtain the reference substance solution.

[0029] In some embodiments, the determination method further comprises calculating the content of impurities by an external standard method.

[0030] In some embodiments, the assay method further comprises preparing a test solution, and the steps of preparing the test solution are as follows: mixing the desloratadine oral solution with a diluent to obtain the test solution.

[0031] In some embodiments, the diluent used is a mobile phase, that is, a mixed solution of potassium hydrogen phosphate buffer, methanol and acetonitrile in a volume ratio of 50:25:25. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 It is the HPLC spectrum of the reference solution.

[0033] Figure 2 It is the HPLC spectrum of the spiked test solution.

[0034] Figure 3It is the HPLC spectrum of the test solution.

[0035] Figure 4 It is the HPLC spectrum of blank solution.

[0036] Figure 5 It is the HPLC spectrum of blank excipient solution.

[0037] Figure 6 It is a high performance liquid chromatography spectrum of mobile phase potassium dihydrogen phosphate buffer (1% triethylamine); wherein, from top to bottom, they are respectively high temperature destruction spiked test solution, reference solution, blank auxiliary material solution and blank solution.

[0038] Figure 7 It is a high performance liquid chromatography spectrum of impurities determined by a method optimized according to the existing determination method; wherein, the spectrum in the Y direction is respectively a mixed solution of the test sample and impurities (i.e., a blue spectrum), a high temperature destroyed test sample solution (i.e., a black spectrum), and an impurity mixed solution (containing impurities) (i.e., a rose-red spectrum). DETAILED DESCRIPTION

[0039] The following will be combined with the embodiments to clearly and completely describe the concept of the present invention and the technical effects produced, so as to fully understand the purpose, characteristics and effects of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, other embodiments obtained by those skilled in the art without creative work are all within the scope of protection of the present invention.

[0040] If the specific conditions are not specified in the examples, the experiments were carried out under conventional conditions or conditions recommended by the manufacturer. If the manufacturers of the reagents or instruments are not specified, they are all conventional products that can be purchased commercially.

[0041] It is worth noting that the "impurities" in this embodiment include desloratadine impurity 1, namely 8-chloro-11-(1-methylpiperidin-4-ylidene)-6,11-dihydro-5H-benzo[5,6]cycloheptyl[1,2-b]pyridine. 1. Main instruments and reagents:

[0042] 1. Main instruments

[0043] (1) High performance liquid chromatograph: Shimadzu LC-2030C series high performance liquid chromatograph;

[0044] (2) Chromatographic column: Symmetry C8, 4.6*150 mm, 5 μm;

[0045] (3) Electronic balance: Sartorius SQP;

[0046] (4) pH meter: Mettler FE28.

[0047] 2. Main reagents

[0048] (1) Potassium hydrogen phosphate, phosphoric acid, and triethylamine were all analytically pure;

[0049] (2) Methanol and acetonitrile were of chromatographic grade.

[0050] 3. Reference substances

[0051] Impurity reference substance: Desloratadine impurity 1, sourced from Guangzhou Junmu Biotechnology Co., Ltd. (product batch number DM20120714), with a content of 98.90%.

[0052] 4. Test products

[0053] Desloratadine oral solution, from Shenzhen Beimei Pharmaceutical Co., Ltd., 60mg / 120mL.

[0054] 2. Preparation of Mobile Phase

[0055] 1. Take 1.57g-1.92g of dipotassium hydrogen phosphate, add 1L of water to dissolve it, add 2.7ml-3.3ml of triethylamine and stir to mix, adjust the pH to 7.1-7.3 with phosphoric acid to obtain dipotassium hydrogen phosphate buffer.

[0056] 2. Take potassium dihydrogen phosphate buffer, methanol and acetonitrile in a volume ratio of 50:25:25 respectively, and mix the three to obtain the mobile phase.

[0057] 3. Determination methods and conditions

[0058] The test solutions were tested using a high performance liquid chromatograph according to the following conditions:

[0059] Chromatographic column: Symmetry C8, 4.6*150mm, 5μm;

[0060] Mobile phase: potassium hydrogen phosphate buffer: methanol: acetonitrile = 50:25:25 (v / v);

[0061] Elution mode: isocratic elution;

[0062] Injection volume: 20-100 μL;

[0063] Flow rate: 1.1-1.3 ml / min;

[0064] Column temperature: 35-45°C;

[0065] Detector: UV detector;

[0066] Detection wavelength: 254±2nm.

[0067] 4. Solution Preparation

[0068] 1. Mobile phase or diluent

[0069] Take 1.74 g of dipotassium hydrogen phosphate, add 1 L of water to dissolve it, add 3 ml of triethylamine and stir to mix, adjust the pH to 7.2 with phosphoric acid, filter, and sonicate to obtain dipotassium hydrogen phosphate buffer;

[0070] Then, potassium hydrogen phosphate buffer, methanol and acetonitrile were measured respectively in a volume ratio of 50:25:25, and the three were mixed to obtain a mobile phase or diluent.

[0071] 2. Reference substance stock solution

[0072] First, weigh about 12.5 mg of desloratadine impurity 1 reference substance, accurately weigh it, put it into a 50 ml volumetric flask, dissolve it with a diluent and dilute it to the mark, shake it well, and use it as the reference substance reserve intermediate solution;

[0073] Then, accurately measure 5 ml of the reference substance reserve intermediate solution, place it in a 50 ml volumetric flask, dilute to the mark with a diluent, and shake well to obtain the reference substance reserve solution;

[0074] 3. Reference solution

[0075] Accurately measure 1 ml of reference substance stock solution, place it in a 20 ml volumetric flask, dilute to the mark with diluent, and shake well to obtain the reference substance solution.

[0076] 4. Test solution

[0077] Take desloratadine oral solution, shake well, accurately measure 10 ml, put it in a 20 ml volumetric bottle, dilute to the scale with diluent, shake well, and you have it.

[0078] 5. Blank excipient solution

[0079] Take excipients with the same prescription ratio as that of the finished desloratadine oral solution to prepare a solution without the active ingredient of desloratadine as a blank excipient; the blank excipient comprises sorbitol, anhydrous citric acid, sodium citrate, disodium edetate, propylene glycol, sodium benzoate, hypromellose and sucralose.

[0080] Accurately measure 10 ml of blank excipient, place it in a 20 ml volumetric flask, dilute to the scale with diluent, shake well, and obtain the blank excipient solution.

[0081] 6. Spiked test solution

[0082] Take desloratadine oral solution, shake well, accurately measure 10 ml, put it in a 20 ml volumetric bottle, add appropriate amount of diluent, then transfer 1 ml of reference stock solution, dilute to the scale with diluent, shake well, and obtain.

[0083] 7. High temperature destroys the test solution

[0084] Take desloratadine oral solution, destroy it at high temperature of 60℃ for 30 days, and prepare it according to the preparation process of the test solution.

[0085] 8. Mixed solution of test sample and impurities

[0086] That is, impurities are added and mixed during the preparation process of the test sample. The specific preparation method is as follows:

[0087] Take desloratadine oral solution that has been destroyed at high temperature of 60°C for 30 days, prepare it according to the preparation process of the test solution, add the stock solution of each impurity reference substance (including impurity 1) before dilution, and prepare a test impurity mixed solution containing the limit concentration of each impurity.

[0088] 9. Impurity mixed solution (including impurity 1)

[0089] Weigh each impurity reference substance, mix them, dilute them with a diluent, and prepare an impurity mixed solution for positioning.

[0090] V. Specific test content

[0091] Example 1

[0092] A method for determining impurities in a desloratadine oral solution, wherein the impurities include a desloratadine impurity 1, and the specific steps are as follows:

[0093] (1) Prepare potassium hydrogen phosphate buffer, mobile phase, reference solution, and test solution according to the above solution preparation method and set aside;

[0094] (2) The reference solution and the spiked test solution were injected into a high performance liquid chromatograph for determination. The chromatographic column was Symmetry C8 (4.6*150 mm, 5 μm), the column temperature was 40°C, the flow rate was 1.2 ml / min, the detection wavelength of the UV detector was 254 nm, the injection volume was 50 μL, the mobile phase was potassium hydrogen phosphate buffer: methanol: acetonitrile = 50:25:25 (v / v), and the elution was isocratic.

[0095] (3) Analyze the obtained HPLC spectrum and calculate the impurity content by external standard method.

[0096] Example 2

[0097] Compared with Example 1, the flow rate was adjusted to 1.1 ml / min. Other chromatographic conditions remained unchanged.

[0098] Example 3

[0099] Compared with Example 1, the flow rate was adjusted to 1.3 ml / min, and other chromatographic conditions remained unchanged.

[0100] Example 4

[0101] Compared with Example 1, the temperature of the chromatographic column was adjusted to 35° C., and other chromatographic conditions remained unchanged.

[0102] Example 5

[0103] Compared with Example 1, the temperature of the chromatographic column was adjusted to 45° C., and other chromatographic conditions remained unchanged.

[0104] Example 6

[0105] Compared with Example 1, the pH of the mobile phase buffer salt was adjusted to 7.1, and other chromatographic conditions remained unchanged.

[0106] Example 7

[0107] Compared with Example 1, the pH of the mobile phase buffer salt was adjusted to 7.3, and other chromatographic conditions remained unchanged.

[0108] Comparative Example 1

[0109] Compared with Example 1, 10 ml of triethylamine was added to the mobile phase buffer salt, and other chromatographic conditions remained unchanged. The HPLC spectrum is shown in Figure 6 .

[0110] Comparative Example 2

[0111] The test was carried out using the method for determining related substances of desloratadine tablets included in the United States Pharmacopoeia USP43. The determination method is shown in Table 1, and the experimental results are shown in Table 4.

[0112] Table 1 Determination methods of related substances in desloratadine tablets included in the United States Pharmacopoeia USP43

[0113]

[0114] Comparative Example 3

[0115] The chromatographic conditions were optimized under the chromatographic conditions of Comparative Example 2, and the detection conditions are shown in Table 2.

[0116] HPLC spectrum reference Figure 7 As described, the results show that the peak position of desloratadine impurity 1 overlaps with the peak position of desloratadine, and it is difficult to adjust the separation effect by replacing the chromatographic column, optimizing the mobile phase elution program, chromatographic column temperature, chromatographic column flow rate and other parameters.

[0117] Table 2 Optimization process methods

[0118]

[0119] Table 3 Comparison of data in various embodiments

[0120]

[0121] Table 4 Comparison of data of various comparative examples

[0122]

[0123] As can be seen from Table 3, Examples 1 to 7 adopt the high performance liquid chromatography detection conditions of the present application, and perform impurity analysis on the desloratadine oral solution containing the desloratadine impurity 1, and the separation degree between the impurity 1 and the adjacent peak is 2.698-3.132, which is greater than 1.5, indicating that the desloratadine impurity 1 and desloratadine can be effectively separated, so that the desloratadine impurity 1 in the desloratadine oral solution can be effectively detected.

[0124] However, when determining the desloratadine impurity 1, the comparative example 1 using the potassium hydrogen phosphate buffer solution containing 1% triethylamine, the comparative example 2 of the existing United States Pharmacopoeia desloratadine tablet related substance determination method, and the comparative example 3 optimized on the basis of comparative example 2, peak overlap occurred, making it difficult to effectively separate the impurity 1 from desloratadine. Therefore, the present invention provides an unprecedented method for determining the desloratadine impurity 1 in the desloratadine oral solution, thereby effectively detecting the desloratadine impurity 1 and achieving effective control of product quality.

[0125] VI. Method Validation

[0126] 1. System adaptability

[0127] The reference solution was tested using the chromatographic conditions of Example 1, and 5 injections were made continuously. The chromatogram was recorded. The results are shown in Table 5 and Figure 1 shown.

[0128] Table 5 Test results of reference solution

[0129]

[0130] In this test, the RSD of the peak area of ​​desloratadine impurity 1 in the reference solution after repeated injection 5 times was 2.3%. Therefore, the system adaptability test showed that the impurity testing method disclosed in the present invention has good system precision.

[0131] 2. Exclusivity

[0132] The blank solution (i.e., mobile phase), reference solution, test solution, blank auxiliary material solution, and spiked test solution were tested using the chromatographic conditions of Example 1, and the chromatograms were recorded. The results are shown in Tables 6 and Figures 2 to 5 shown.

[0133] Table 6 Test results of different solutions

[0134]

[0135] The results showed that the determination method of impurities in desloratadine oral solution had good specificity.

[0136] 3. Limit of Quantitation and Limit of Detection

[0137] Take appropriate amount of desloratadine impurity 1 reference substance, dilute and dissolve it with diluent, and dilute it step by step until the signal-to-noise ratio S / N of the main component is greater than 10, which is the quantitative limit solution, and the signal-to-noise ratio S / N of the main component is greater than 3, which is the detection limit solution.

[0138] The detection limit results are shown in Table 7.

[0139] Table 7 Detection limit results of desloratadine impurity 1

[0140] Compound Concentration (μg / ml) Concentration ratio to test sample (%) S / N Impurities 0.1287 0.05 20.19

[0141] The quantification limit results are shown in Table 8.

[0142] Table 8 Desloratadine Impurity 1 Limit of Quantitation Results

[0143] Compound Concentration (μg / ml) Concentration ratio to test sample (%) S / N Impurities 0.2573 0.10 69.90

[0144] The results showed that the detection limit of desloratadine impurity 1 was 0.1287 μg / ml, and the signal-to-noise ratio was 20.19, which was equivalent to 0.05% of the test solution concentration and could be effectively detected. The quantification limit of desloratadine impurity 1 was 0.2573 μg / ml, and the signal-to-noise ratio was 69.90, which was equivalent to 0.10% of the test solution concentration and could be accurately quantified, indicating good sensitivity of the method.

[0145] 4. Accuracy test

[0146] Take the impurity reference substance stock solution and blank excipient solution, and prepare the limit concentration 50% to 150% horizontal accuracy solution according to the preparation method in Table 9. Prepare 3 copies in parallel for each concentration level and inject them separately.

[0147] Table 9 Horizontal Accuracy Solution Preparation Table

[0148]

[0149] The detection was carried out according to the above chromatographic conditions, the chromatogram was recorded, and the recovery rate of impurities at a concentration level of 50% to 150% was calculated. The results are shown in Table 10. Acceptable standard: the recovery rate is between 90% and 110%, and the recovery rate RSD is ≤10%.

[0150] Table 10 Recovery of impurities at concentration levels of 50% to 150%

[0151]

[0152]

[0153] The results show that at the limit concentration level of 50%-150%, the impurity recovery rate is between 97% and 105%, and the recovery rate RSD is 5.1%. The determination method of the present invention has good accuracy.

[0154] 5. Effect of determination method on sample test results

[0155] The finished product of desloratadine oral solution (sourced from Shenzhen Beimei Pharmaceutical Co., Ltd.) was subjected to stability tests for 0, 6 and 24 months. At the same time, two types of desloratadine oral solutions sold by other manufacturers on the market were purchased for stability tests. The solutions were prepared according to the above-mentioned test solution preparation method and tested. The test results are shown in Table 11.

[0156] Table 11 Test results of stability samples by determination method

[0157] Serial number Sample name Impurity 1 test results 1 Finished product stability 0 month Not detected 2 Finished product stability accelerated by 6 months Not detected 3 The stability of the finished product is 24 months (end of validity period) Not detected 4 Manufacturer 1 Desloratadine oral solution is valid for 12 months 0.07％ 5 Manufacturer 1 Desloratadine Oral Solution Accelerated 6 Months 0.07％ 6 Manufacturer 2 Desloratadine oral solution valid for 12 months 0.05％ 7 Manufacturer 2 Desloratadine Oral Solution Accelerated 6 Months 0.05％

[0158] The results showed that the determination method showed no detection results for the finished product at 0 month, accelerated 6 month, and long-term 24 month tests, while the stability tests of 2 desloratadine oral solutions from other manufacturers detected impurity 1 at contents of 0.07% and 0.05%, respectively. This indicates that the technical solution of the present application can effectively detect desloratadine impurity 1 in desloratadine oral solution and can detect the specific content of desloratadine impurity 1.

[0159] In summary, through the above exploration and verification experiments, the validity and reliability of the determination method of this application are determined.

[0160] The above are only some embodiments of the present invention. For those skilled in the art, several modifications and improvements can be made without departing from the creative concept of the present invention, which all belong to the protection scope of the present invention.

Claims

1. A method for determining impurities in a desloratadine oral solution, characterized in that: The impurities include desloratadine impurity 1, and the determination method adopts high performance liquid chromatography, and the detection conditions of the high performance liquid chromatography include: Chromatographic column: octylsilane bonded silica gel column or column with equivalent performance; Detection wavelength: 254±2nm; Detector: UV detector; Column temperature: 35-45°C; Flow rate: 1.1-1.3 mL / min; Mobile phase: potassium hydrogen phosphate buffer, methanol and acetonitrile; Elution mode: isocratic elution.

2. The method for determining impurities in the desloratadine oral solution according to claim 1, characterized in that: The volume ratio of the dipotassium hydrogen phosphate buffer, methanol and acetonitrile is 50:25:

25.

3. The method for determining impurities in the desloratadine oral solution according to claim 1, characterized in that: The pH value of the dipotassium hydrogen phosphate buffer is 7.1-7.

3.

4. The method for determining impurities in the desloratadine oral solution according to claim 3, characterized in that: The preparation method of the dipotassium hydrogen phosphate buffer is as follows: take 1.57g-1.92g of dipotassium hydrogen phosphate, add 1L of water to dissolve it, add 2.7ml-3.3ml of triethylamine and stir to mix well, and adjust the pH to 7.1-7.3 with phosphoric acid.

5. The method for determining impurities in desloratadine oral solution according to any one of claims 1 to 4, characterized in that: The detection wavelength was 254 nm, the column temperature was 40° C., and the flow rate was 1.2 mL / min.

6. The method for determining impurities in desloratadine oral solution according to any one of claims 1 to 4, characterized in that: The octylsilane bonded silica gel column is a Symmetry C8 chromatographic column, which is 150 mm long, 4.6 mm in inner diameter, and has a filler particle size of 5 μm.

7. The method for determining impurities in desloratadine oral solution according to any one of claims 1 to 4, characterized in that: The injection volume of the HPLC method is 20-100 μL.

8. The method for determining impurities in desloratadine oral solution according to any one of claims 1 to 4, characterized in that: The determination method further comprises the preparation of a reference solution, and the preparation of the reference solution comprises the following steps: S1. Take the impurity reference substance, weigh it accurately, dissolve it with a diluent and dilute it as the reference substance reserve intermediate solution; S2. Accurately measure the reference substance reserve intermediate solution and dilute it with a diluent to obtain the reference substance reserve solution; S3. Accurately measure the reference substance stock solution and dilute it with a diluent to obtain the reference substance solution.

9. The method for determining impurities in desloratadine oral solution according to claim 8, characterized in that: The determination method further comprises preparing a test solution, and the test solution preparation steps are as follows: mixing the desloratadine oral solution with a diluent to obtain the test solution.

10. The method for determining impurities in desloratadine oral solution according to claim 9, characterized in that: The determination method also includes calculating the content of the impurity by an external standard method.

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