Method for detecting desloratadine oral liquid related substances

Abstract

The invention provides a method for detecting related substances of desloratadine oral liquid, which is applicable to the technical field of detection of impurity control of organic chemical synthesis raw material medicines, particularly to the field of medicine quality control, and is a liquid chromatography detection method needing to monitor oxidation impurities and byproducts. The analysis method overcomes the limitation of a method for isocratic elution of desloratadine related substances, phosphoric acid is adopted to replace trifluoroacetic acid, the sensitivity and the accuracy are improved, the problems of low detection efficiency and low precision in the prior art are solved, and the separation degree and the detection efficiency are improved by optimizing conditions such as mobile phase composition and the like. A chromatographic column is a silica gel bonded octadecyl silane column and an ultraviolet detector, a mobile phase comprises a phosphate buffer solution added with SDS and an organic solvent, the mobile phase is simple in composition, a conventional chromatographic column is used, the cost is reduced, and a gradient elution mode is adopted for separation and detection. The method for detecting the desloratadine syrup-related substances is good in separation degree, high in specificity, high in precision and good in repeatability, and meets methodological research on determination of the desloratadine oral liquid-related substances.

Description

Technical Field

[0001] The present invention relates to the technical field of chemical drug synthesis and oral solution analysis of preparations, and particularly relates to an analytical detection method for analyzing and determining related substances in loratadine oral solution by liquid chromatography; Background Art

[0002] As a second-generation antihistamine drug and the active metabolite of loratadine, loratadine exerts its effect by selectively antagonizing histamine H1 receptors. It has advantages such as rapid onset, long-lasting effect, and weak central inhibitory effect. Clinically, it is widely used in the treatment of allergic diseases such as allergic rhinitis (seasonal / perennial) and chronic idiopathic urticaria. Especially in pediatric patients, it is highly favored due to its friendly taste and high safety. Its quality control is crucial for safety and efficacy. In the field of analytical detection, existing methods such as the HPLC methods in EP and USP have problems such as excipient interference, low detection efficiency, insufficient resolution, and low precision. Therefore, it is necessary to develop an analytical method with simple operation, good separation effect, and high detection accuracy to meet the requirements of drug quality control.

[0003] Loratadine, its molecular formula is C 19 H 19 ClN2, and its molecular weight is 310.82:

[0004] In the process of investigating the degradation impurities and stability of loratadine oral solution, quality analysis is crucial for the impurity control of loratadine oral solution. And an analytical method for related substances in loratadine oral solution can guide and detect the impurity risk of loratadine oral solution, ensuring the safety, effectiveness, and consistency of the drug, thus having important practical significance in the quality control of loratadine oral solution. Summary of the Invention

[0005] The present invention provides an analytical detection method for related substances in loratadine oral solution, which can quickly, effectively, and accurately monitor the related substances in loratadine oral solution and achieve the quality control of its final product oral solution.

[0006] The present invention provides an analytical detection method for related substances in loratadine oral solution. The high-performance liquid chromatography method is adopted, with a silica-bonded octadecylsilane column as the chromatographic column, a mixed solution containing SDS and phosphate as mobile phase A, and pure organic solvent as mobile phase B for gradient elution.

[0007] The gradient elution program is as follows:

[0008] Preferably, the organic phase is pure acetonitrile.

[0009] Preferably, the provided chromatographic column is ACE Excel 3 Super C18 (4.6 mm × 150 mm, 3 µm).

[0010] The analytical determination method described in the present invention can be tested according to the following method: Example

[0011] 1) Diluent: Methanol; 2) System suitability solution: Take appropriate amounts of loratadine and impurity (A, B, C, D, E) reference substances, dissolve them with the diluent and prepare a mixed solution containing 0.08 mg of loratadine and 0.12 μg of each of the impurity (A, B, C, D, E) reference substances per 1 ml; 3) Blank excipient solution: Measure 15 ml of blank excipient, place it in a 100 ml volumetric flask, dilute it to the mark with the solvent, and shake well to obtain; 4) The flow rate of the mobile phase is preferably 1.0 mL / min, the ultraviolet wavelength is 280 nm, the column oven temperature is 35 °C, and the injection volume is 30 μl; 5) Elution method: Gradient elution 6) High performance liquid chromatograph: 1260Ⅱ; 7) Precisely measure 30 μl of the solutions in 1), 2), and 3) above, inject them into the liquid chromatograph respectively, and record the chromatogram.

[0012] The present invention uses an ACE Excel 3 Super C18 chromatographic column, mobile phase A is a mixed buffer solution of SDS and phosphate, mobile phase B is acetonitrile, and the ultraviolet absorption wavelength is 280 nm and other chromatographic conditions, which can effectively separate loratadine and its impurities completely. The present invention uses an HPLC analysis method to solve the separation and determination problem of loratadine and its impurities, thereby reducing the occurrence of side reactions, controlling the impurity risk, excluding the interference of excipients, evaluating the stability and optimizing the process, and achieving the goal of monitoring that every drop of oral liquid is safe, effective and controllable. Description of the Drawings

[0013] Figure 1 It is the HPLC chart when it is Example 1. Detailed Embodiments The following examples are used to further understand the present invention, but are not limited to the scope of this implementation.

[0015] For use in the example Instruments and Conditions High performance liquid chromatograph: 1260Ⅱ Chromatographic column: ACE Excel 3 Super C18 (4.6 mm × 150 mm, 3 µm); Mobile phase A: (0.01 mol / L potassium dihydrogen phosphate and 0.002 mol / L SDS, added with 0.1% phosphoric acid): acetonitrile (900:100); Mobile phase B: acetonitrile Column oven temperature: 35 °C; Injection volume: 30 μl; UV wavelength: 280 nm; Elution mode: gradient elution

[0016] Figure 1 The elution order of desloratadine and its impurities is impurity E, impurity A, impurity D, main component, impurity B, impurity C; From Figure 1 It shows that: the method of the present invention, using the same HPLC analysis method, can separate desloratadine and its impurities, and can accurately perform quantitative detection, thereby effectively controlling the product quality of desloratadine oral solution.

Claims

1. An analytical detection method for related substances of desloratadine oral solution, using high performance liquid chromatography. The chromatographic column is a silica gel bonded octadecylsilane column, with an ultraviolet detector. A phosphate buffer solution containing SDS and an organic solvent are used as the mobile phase for gradient elution, which can completely separate desloratadine and its impurities.

2. According to the analytical detection method described in claim 1, the buffer salt is selected from sodium dihydrogen phosphate or potassium dihydrogen phosphate and an anionic surfactant, and the organic phase is selected from acetonitrile or methanol.

3. According to the analytical detection method described in claim 1, both desloratadine and its impurities have ultraviolet absorption wavelengths in the range of 190 - 400 nm, so an ultraviolet detector is selected.

4. According to the analytical detection method described in claim 1, the elution gradient process is as follows:

5. According to the analytical detection method described in claim 1, the preferred length of the chromatographic column is 150 mm, the diameter is 4.6 mm, and the particle size of the packing is 3 µm.

6. According to the analytical detection method described in claim 2, mobile phase A is preferably a mixed buffer solution of SDS and potassium dihydrogen phosphate, and mobile phase B is preferably pure acetonitrile.

7. According to the analytical detection methods described in claims 1 and 3, it includes the following steps: ① Set the flow rate to 0.5 - 1.5 ml / min;; ② The column temperature of the chromatographic column is 30 - 50 °C; ④ The injection volume is 10 - 50 µl.

8. According to the analytical detection method described in claim 7, the chromatographic conditions are optimized as follows: 1 The flow rate is preferably 1.0 ml / min; ② The column temperature is preferably 35 °C; ③ The injection volume is preferably 30 µl.

9. According to the analytical detection method described in claim 3, the structural formulas of the desloratadine and its impurities are:

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