A method for analyzing and detecting related substances of desloratadine
By using high-performance liquid chromatography in the detection of deloratadin, adjusting the mobile phase composition and pH value, the problem of overlapping impurity A and the main peak in the existing detection methods is solved, and efficient separation and high-precision detection effects are achieved.
Patent Information
- Application Number
- CN202510084634.8
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-01-20
- Publication Date
- 2025-04-08
AI Technical Summary
The existing deloratadine detection method cannot efficiently achieve the separation of all relevant substances, and impurity A coincides with the main peak, and the separation is poor, resulting in low detection accuracy.
The detection was performed by high-performance liquid chromatography. By adjusting the composition and pH of the mobile phase, and using isometric elution, the column temperature was increased to 39℃~41℃ to achieve effective separation of each impurity.
It has achieved efficient separation of deloratadin-related substances, good separation degree, impurity A, etc. do not overlap with the main peak, quantitative limit, high detection accuracy and high efficiency.
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Abstract
Description
Technical Field
[0001] The invention relates to a method for analyzing and detecting related substances of desloratadine, and belongs to the technical field of drug detection and analysis. Background Art
[0002] Desloratadine, chemical name 8-chloro-6,11-dihydro-11-(4-piperidinyl)-5H-benzo[5,6]heptylcyclo[1,2-b]pyridine, is a non-sedating, long-acting tricyclic antihistamine that selectively acts on H1 receptors. It is an active metabolite obtained from ethyl formate in the body, and relieves allergic rhinitis or chronic idiopathic urticaria and other related symptoms. The chemical structure of desloratadine is:
[0003]
[0004] The synthesis of desloratadine is mainly prepared by the hydrolysis of loratadine, but no matter which route is used for synthesis, the quality of the final product desloratadine must meet the drug requirements of the human body, especially the control of impurities therein is also crucial. For the detection and analysis of drugs, there are also many existing literature reports, including the detection and analysis of desloratadine in various countries, such as the Chinese Pharmacopoeia and the United States Pharmacopoeia, but the detection and analysis methods in the above-mentioned pharmacopoeias cannot completely analyze all the related substances, and there are many related substances brought in during the synthesis process of desloratadine and the previous step.
[0005] Desloratadine related substances include impurity A (N-methylisodesloratadine, CAS No.: 183198-48-3), impurity B (isodesloratadine, CAS No.: 183198-49-4), impurity C (N-oxidized desloratadine, CSA No.: 169253-26-3), impurity D (N-acetyl loratadine, CAS No.: 183198-49-4), impurity E (N-methyldesloratadine, CAS No.: 38092-89-6), impurity F (N-formyl loratadine, CAS No.: 117810-61-4), impurity G (loratadine, CAS No.: 79794-75-5) and impurity H (dehydrodesloratadine, CAS No.: 117811-20-8). The structural formulas of the impurity compounds of the above-mentioned related substances are shown as follows:
[0006]
[0007] Specifically, the liquid chromatography conditions in the analytical method for desloratadine related substances disclosed in the Chinese Pharmacopoeia CHP2010 are:
[0008] The mobile phase uses buffer-acetonitrile, and the volume ratio is (57:43), where the buffer is 0.865g sodium dodecyl sulfate dissolved in 1000ml water, and 0.5ml trifluoroacetic acid is added; isocratic elution is used, the detection wavelength is 280nm, the column temperature is 35℃, the flow rate is 1ml / min, and the injection volume is 20μl. This method cannot simultaneously analyze all related substances during the detection process, and impurity A overlaps with the main peak, and the separation between the impurity E peak and the main peak is poor, and the accuracy is not high. It is impossible to detect and analyze impurities A and E. The United States Pharmacopoeia USP43 <1> The liquid phase detection conditions disclosed in are:
[0009] The mobile phase is buffer-acetonitrile, and the volume ratio is (57:43), wherein the buffer is 0.865g of sodium dodecyl sulfate dissolved in 1000ml of water, and 0.5ml of trifluoroacetic acid is added; isocratic elution is adopted, the detection wavelength is 280nm, the column temperature is 35℃, the flow rate is 1ml / min, and the injection volume is 100μl. Under the chromatographic conditions, the peak of impurity A coincides with the main peak. This method also cannot simultaneously analyze all related substances during the detection process, and the above CHP2010 and USP4 <1> The common characteristics of the detection methods in the above methods are that impurity A cannot be separated from the main peak, and the response of the main peak is not high, which is not conducive to improving the efficiency of detection and the quality of analysis. Summary of the invention
[0010] The present invention aims at solving the problems existing in the above prior art and provides a method for analyzing and detecting related substances of desloratadine, in order to solve the problem that the existing detection method cannot efficiently separate all the related substances in desloratadine and the detection accuracy is poor.
[0011] The object of the present invention is achieved by the following technical scheme: a method for analyzing and detecting related substances of desloratadine, wherein the method adopts high performance liquid chromatography for detection, and the high performance liquid chromatography includes the following chromatographic conditions:
[0012] The elution method was isocratic elution;
[0013] Mobile phase: sodium dodecyl sulfate, sodium dihydrogen phosphate, triethylamine, acetonitrile, a mixture of methanol and water is used as the mobile phase, and phosphoric acid is used to adjust the pH value of the mobile phase to 2.8-3.3; 1.0g-1.1g sodium dodecyl sulfate and 0.86g-0.88g sodium dihydrogen phosphate are contained in each 550ml of water in the mobile phase; the volume ratio of water: triethylamine: acetonitrile: methanol in the mobile phase is 550: 1.4-1.6: 285-320: 145-156;
[0014] Column temperature: 39℃~41℃;
[0015] Detection wavelength: 280nm.
[0016] The present invention improves the detection conditions, so that each impurity in the analysis and detection of related substances of desloratadine can have peaks and can be separated from each other, the separation degree is good, the quantitative limit can be passed, and the peaks of each impurity such as impurity A and the main peak do not overlap, and high-efficiency detection can be effectively realized, and the peak conditions of each impurity can be analyzed, with the effect of high detection accuracy. Specifically, the present invention improves the mobile phase in the detection conditions and adopts an isocratic elution method, that is, the mobile phase is a mixture of sodium dodecyl sulfate, sodium dihydrogen phosphate, triethylamine, acetonitrile and methanol and water as the mobile phase, and raw materials such as sodium dihydrogen phosphate, triethylamine and methanol are added to the mobile phase system, and the pH value is adjusted to 2.8-3.3 by phosphoric acid, avoiding the addition of trifluoroacetic acid, and at the same time, the column temperature is increased to 39°C-41°C for detection, so that in the analysis and detection of desloratadine, each impurity can be effectively peaked and separated, and related substances such as impurity A do not overlap with the main peak, and the detection limit with good separation can meet the requirements, and the advantage of efficient detection is achieved. As a further preference, it is best to use phosphoric acid to adjust the pH value to 3.0-3.1, and the temperature of the column temperature is controlled at 40°C. As a further preference, the mobile phase is: a mixture of sodium dodecyl sulfate, sodium dihydrogen phosphate, triethylamine, acetonitrile, methanol and water as the mobile phase, and the pH value of the mobile phase is adjusted to 3.0 with phosphoric acid; every 550 ml of water in the mobile phase contains 1.1 g of sodium dodecyl sulfate and 0.86 g of sodium dihydrogen phosphate; the volume ratio of water: triethylamine: acetonitrile: methanol in the mobile phase is 550:1.5:300:150.
[0017] In the above-mentioned method for analyzing and detecting related substances of desloratadine, preferably, the chromatographic column used in the high performance liquid chromatography is a reverse pentafluoro chromatographic column. It is used to further improve the accuracy of the detection and analysis, and can also better ensure that the impurities are effectively separated and non-overlapping during detection. As a further preference, the reverse pentafluoro chromatographic column is a Shim-pack velox PFPP chromatographic column, and the Shim-pack velox PFPP chromatographic column has a column length of 250 mm, an inner diameter of 4.6 mm, and a particle size of 5 μm. The chromatographic column here can also be described as Shim-pack velox PFPP 4.6*250mm 5μm.
[0018] In the above-mentioned method for analyzing and detecting related substances of desloratadine, preferably, the high performance liquid chromatography method further comprises the following chromatographic conditions:
[0019] The injection volume is 10μl~15μl;
[0020] Flow rate: 1.0ml / min~1.2ml / min;
[0021] The detection running time is 40min to 50min.
[0022] In the above-mentioned method for analyzing and detecting related substances of desloratadine, preferably, the related substances of desloratadine include impurity A, impurity B, impurity C, impurity D, impurity E, impurity F, impurity G and impurity H; the structural formulas of the impurities of the related substances are as follows:
[0023]
[0024] By using the above detection method, it can be effective that in the detection and analysis of desloratadine, the eight impurities of impurity A, impurity B, impurity C, impurity D, impurity E, impurity F, impurity G and impurity H can be separated and peaked, and they do not overlap with the peak of the main peak, which has the advantage of good separation. As a further preference, the impurity A, impurity B, impurity C, impurity D, impurity E, impurity F, impurity G and impurity H can be separated from each other and peaked, and the separation degree is greater than 1.5.
[0025] In summary, compared with the prior art, the present invention has the following advantages:
[0026] 1. The method can make the related substances of desloratadine to have peaks in the analysis and detection and be separated from each other, with good separation degree, and the quantitative limit can be passed, and the peaks of impurities such as impurity A and the main peak do not overlap, so as to achieve efficient detection and analysis, and can also analyze the peaks of each impurity, with the effect of high detection accuracy.
[0027] 2. The present invention adds raw materials such as sodium dihydrogen phosphate, triethylamine and methanol to the mobile phase system and adjusts the dosage ratio of each component, and uses phosphoric acid to adjust the pH value to 2.8-3.3, thereby avoiding the addition of trifluoroacetic acid. At the same time, the column temperature is increased to 39° C.-41° C. for detection, so that in the analysis and detection of desloratadine, each impurity can effectively be peaked and separated, and related substances such as impurity A do not overlap with the main peak, and the detection limit has a good separation degree and can meet the requirements, thereby achieving the advantage of efficient detection. BRIEF DESCRIPTION OF THE DRAWINGS
[0028] Figure 1 It is the high performance liquid chromatography analysis chart of the M1 solution in Example 1.
[0029] Figure 2 It is the high performance liquid chromatography analysis chart of the M2 solution in Example 1.
[0030] Figure 3It is the high performance liquid chromatography analysis chart of the M3 solution in Example 1.
[0031] Figure 4 It is a high performance liquid chromatography analysis chart of the quantitative limit LOQ solution in Example 1.
[0032] Figure 5 M in Comparative Example 1 11 HPLC analysis of the solution.
[0033] Figure 6 M in Comparative Example 1 21 HPLC analysis of the solution.
[0034] Figure 7 M in Comparative Example 2 11 HPLC analysis of the solution.
[0035] Figure 8 is to compare M in column 2 21 HPLC analysis of the solution. DETAILED DESCRIPTION
[0036] The technical solution of the present invention is further specifically described below through specific embodiments and drawings, but the present invention is not limited to these embodiments.
[0037] Example 1
[0038] Impurity A standard stock solution C1: Accurately weigh 5.199 mg of impurity A standard into a 50 ml volumetric flask, add diluent to dissolve and dilute to the scale, and shake well.
[0039] Impurity B standard stock solution C2: Accurately weigh 5.210 mg of impurity B standard into a 50 ml volumetric flask, add diluent to dissolve and dilute to the scale, and shake well.
[0040] Impurity C standard stock solution C3: Accurately weigh 5.210 mg of impurity C standard into a 50 ml volumetric flask, add diluent to dissolve and dilute to the scale, and shake well.
[0041] Impurity D standard stock solution C4: Accurately weigh 5.205 mg of impurity D standard into a 50 ml volumetric flask, add diluent to dissolve and dilute to the scale, and shake well.
[0042] Impurity E standard stock solution C5: Accurately weigh 5.122 mg of impurity E standard into a 50 ml volumetric flask, add diluent to dissolve and dilute to the scale, and shake well.
[0043] Impurity F standard stock solution C6: Accurately weigh 5.222 mg of impurity F standard into a 50 ml volumetric flask, add diluent to dissolve and dilute to the scale, and shake well.
[0044] Impurity G standard stock solution C7: Accurately weigh 5.040 mg of impurity B standard into a 50 ml volumetric flask, add diluent to dissolve and dilute to the scale, and shake well.
[0045] Impurity H standard stock solution C8: Accurately weigh 5.220 mg of impurity H standard into a 50 ml volumetric flask, add diluent to dissolve and dilute to the scale, and shake well.
[0046] Desloratadine standard stock solution C9: Accurately weigh 5.210 mg of desloratadine standard into a 50 ml volumetric flask, add diluent to dissolve and dilute to the scale, and shake well.
[0047] The following is a determination of the solubility of each impurity, as shown in Table 1.
[0048] Table 1:
[0049]
[0050]
[0051] In the above solution preparation process, the mobile phase is used as the diluent.
[0052] During the detection and analysis process, the HPLC conditions were as follows:
[0053] Chromatographic column: Shim-pack velox PFPP 4.6*250mm 5μm, which is equivalent to a Shim-pack velox PFPP column with a column length of 250mm, an inner diameter of 4.6mm, and a particle size of 5μm;
[0054] The elution method was isocratic elution;
[0055] Mobile phase: sodium dodecyl sulfate, sodium dihydrogen phosphate, triethylamine, acetonitrile, a mixture of methanol and water as the mobile phase, and phosphoric acid is used to adjust the pH value of the mobile phase to 3.0;
[0056] The mobile phase contains 1.1 g of sodium dodecyl sulfate and 0.86 g of sodium dihydrogen phosphate, 1.5 ml of triethylamine, 300 ml of acetonitrile and 150 ml of methanol per 550 ml of water.
[0057] Column temperature: 40°C;
[0058] Detection wavelength: 280nm;
[0059] The injection volume was 10 μl;
[0060] Flow rate: 1.0 ml / min;
[0061] The test run time is 40min;
[0062] Test solution: 0.5 mg / ml.
[0063] The solutions of each impurity and the desloratadine standard in Table 1 were respectively selected for detection and analysis to locate the peaks of each impurity (impurity A, impurity B, impurity C, impurity D, impurity E, impurity F, impurity G, impurity H), as shown in Table 2 below:
[0064] Table 2:
[0065] Serial number name Peak time (min) 1 Impurity C 6.730 2 Impurity F 10.078 3 Impurity D 11.216 4 Impurity H 14.060 5 Impurity B 14.916 6 Impurity A 15.896 7 Desloratadine 16.944 8 Impurity E 18.272 9 Impurity G 27.301
[0066] The same HPLC conditions for impurity detection were used to detect and analyze M1, M2, M3, test sample solution, LOQ solution, etc. The specific analysis results are shown in Tables 3, 4 and 5, as well as Figure 1 , Figure 2 and Figure 3 The results are shown in Table 3 and Figure 1 is the HPLC chromatogram and data analysis of M1 solution; Table 4 and Figure 2 is the HPLC chromatogram and data analysis of M2 solution; Table 5 and Figure 3 It is the HPLC chromatogram of the LOQ solution and the data analysis instructions.
[0067] Table 3:
[0068] Serial number name Peak time (min) Separation 1 Impurity C 6.694 - 2 Impurity F 10.083 12.0 3 Impurity D 11.226 3.8 4 Impurity H 14.062 9.1 5 Impurity B 14.935 2.4 6 Impurity A 15.911 2.5 7 Desloratadine 16.949 2.5 8 Impurity E 18.278 3.0 9 Impurity G 27.330 16.4
[0069] From the above Table 3 and Figure 1 It can be seen from the results that the detection method of the present invention can effectively separate all impurities with good separation degree, and there will be no overlap of impurity A and the like with the main peak. In addition, one detection can efficiently analyze and determine the peak and detection status of each impurity, thereby achieving a more accurate analysis purpose.
[0070] Table 4:
[0071]
[0072] From Table 4 and Figure 2 It can also be seen that the detection conditions of the present invention can effectively separate the impurities and have the advantage of high separation degree. At the same time, it has the effect of excellent peak shape of the main peak and high peak response value.
[0073] Table 5 above selects the M3 solution in Table 1 for HPLC analysis, and the specific analysis is shown in Table 5 (M3 test results) below:
[0074] Table 5:
[0075] Serial number name concentration Signal-to-Noise Ratio (S / N) 1 Impurity C 0.1％ 72.8 2 Impurity F 0.1％ 80.4 3 Impurity D 0.1％ 73.8 4 Impurity H 0.1％ 82.1 5 Impurity B 0.1％ 30.3 6 Impurity A 0.1％ 66.3 7 Desloratadine 0.1％ 55.8 8 Impurity E 0.1％ 46.4 9 Impurity G 0.1％ 24.8
[0076] From the analysis data in Table 5 and Figure 3 It can be seen from the test results in that the specific detection method can meet the corresponding signal-to-noise ratio requirements.
[0077] Table 6 below shows the results of HPLC analysis of the LOQ solution. Figure 4 It can be seen that it also shows excellent limit of quantification requirements, which meets the limit of quantification requirements required for high performance liquid chromatography detection.
[0078] Table 6:
[0079]
[0080]
[0081] The test solution in Table 1 was selected for high performance liquid chromatography analysis. The specific analysis results are shown in Table 7 (test results of the test solution):
[0082] Table 7:
[0083] Serial number name Peak time (min) Separation 1 Desloratadine 16.935 - 2 Unknown impurities 27.328 19.3
[0084] From the above Tables 3 to 7 and Figure 1-Figure 4 It can be seen that under the chromatographic conditions of the above-mentioned liquid chromatography of the present invention, each impurity can emit peaks and can be separated from each other, the signal-to-noise ratio and the quantitative limit can pass the requirements, it can be suitable for the detection and analysis of desloratadine, and the detection, analysis and control of all related substances of desloratadine can be achieved by a single detection, which has the advantages of convenient detection and high efficiency.
[0085] Example 2
[0086] The corresponding analysis is performed according to each specific analysis process in Example 1, except that the liquid chromatography detection conditions are set within the following range for analysis. The high performance liquid chromatography method of this embodiment includes using the following chromatographic conditions instead for implementation:
[0087] Chromatographic column: Shim-pack velox PFPP 4.6*250mm 5μm, which is equivalent to a Shim-pack velox PFPP column with a column length of 250mm, an inner diameter of 4.6mm, and a particle size of 5μm;
[0088] The elution method was isocratic elution;
[0089] Mobile phase: sodium dodecyl sulfate, sodium dihydrogen phosphate, triethylamine, acetonitrile, a mixture of methanol and water is used as the mobile phase, and phosphoric acid is used to adjust the pH value of the mobile phase to 2.8-3.3; 1.0g-1.1g sodium dodecyl sulfate and 0.86g-0.88g sodium dihydrogen phosphate are contained in each 550ml of water in the mobile phase; the volume ratio of water: triethylamine: acetonitrile: methanol in the mobile phase is 550: 1.4-1.6: 285-320: 145-156;
[0090] Column temperature: 39℃~41℃;
[0091] Detection wavelength: 280nm;
[0092] The injection volume is 10μl~15μl;
[0093] Flow rate: 1.0ml / min~1.2ml / min;
[0094] The detection running time is 40min to 50min.
[0095] When the detection condition parameters of the liquid chromatography of the present invention are set and adjusted within the above range, the peak elution time is shifted accordingly, but each impurity can elute and can be separated from each other, the signal-to-noise ratio and the quantitative limit can pass the requirements, and it can be applied to the detection and analysis of desloratadine. The detection, analysis and control of all the related substances of desloratadine can be achieved by one detection, and it has the advantages of convenient detection and high efficiency, and impurity A and the like will not overlap and interfere with the main peak.
[0096] Comparative Example 1
[0097] In order to illustrate that the detection method of the present invention can effectively separate the impurities and that impurity A does not overlap with the main peak, this comparative example is analyzed and compared by using the liquid phase detection method of desloratadine in the Chinese Pharmacopoeia (ChP2010).
[0098] Impurity A Standard Stock Solution C 11 : Accurately weigh 5.217 mg of impurity A standard into a 50 ml volumetric flask, add diluent to dissolve and dilute to the scale, and shake well.
[0099] Impurity B Standard Stock Solution C 21 : Accurately weigh 5.228 mg of impurity B standard into a 50 ml volumetric flask, add diluent to dissolve and dilute to the scale, and shake well.
[0100] Impurity C Standard Stock Solution C 31 : Accurately weigh 5.205 mg of impurity C standard into a 50 ml volumetric flask, add diluent to dissolve and dilute to the scale, and shake well.
[0101] Impurity D Standard Stock Solution C 41 : Accurately weigh 5.200 mg of impurity D standard into a 50 ml volumetric flask, add diluent to dissolve and dilute to the scale, and shake well.
[0102] Impurity E Standard Stock Solution C 51 : Accurately weigh 5.120 mg of impurity E standard into a 50 ml volumetric flask, add diluent to dissolve and dilute to the scale, and shake well.
[0103] Impurity F Standard Stock Solution C 61 : Accurately weigh 5.208 mg of impurity F standard into a 50 ml volumetric flask, add diluent to dissolve and dilute to the scale, and shake well.
[0104] Impurity G Standard Stock Solution C 71 : Accurately weigh 5.018 mg of impurity B standard into a 50 ml volumetric flask, add diluent to dissolve and dilute to the scale, and shake well.
[0105] Impurity H Standard Stock Solution C 81 : Accurately weigh 5.200 mg of impurity H standard into a 50 ml volumetric flask, add diluent to dissolve and dilute to the scale, and shake well.
[0106] Desloratadine Standard Stock Solution C 91 : Accurately weigh 5.200 mg of desloratadine standard into a 50 ml volumetric flask, add diluent to dissolve and dilute to the scale, and shake well.
[0107] Table 8 below shows the preparation of fixed volume solutions of various impurities.
[0108] Table 8:
[0109]
[0110] During the detection and analysis process, the HPLC conditions were as follows:
[0111] Chromatographic column: YMC J'sphere ODS-M80 4.6*150mm 4μm;
[0112] The elution method was isocratic elution;
[0113] Mobile phase: a mixture of buffer solution and acetonitrile, wherein the volume ratio of buffer solution to acetonitrile is 57:43, and the buffer solution is prepared by dissolving 0.865 g of sodium dodecyl sulfate in 1000 ml and adding 0.5 ml of trifluoroacetic acid.
[0114] Column temperature: 35°C;
[0115] Detection wavelength: 280nm;
[0116] The injection volume was 20 μl;
[0117] Flow rate: 1.0 ml / min;
[0118] The test run time is 50min;
[0119] Test solution: 0.5 mg / ml.
[0120] The solutions of each impurity and the desloratadine standard in Table 8 were respectively selected for detection and analysis to locate the peaks of each impurity (impurity A, impurity B, impurity C, impurity D, impurity E, impurity F, impurity G, impurity H), as shown in Table 9 below:
[0121] Table 9:
[0122] Serial number name Peak time (min) 1 Impurity C 7.906 2 Impurity F 11.411 3 Impurity D 12.145 4 Impurity H 21.478 5 Impurity B 22.534 6 Impurity A 24.214 7 Desloratadine 24.390 8 Impurity E 26.526 9 Impurity G 34.776
[0123] The same HPLC conditions as above were used to detect each impurity. 11 、M 21 , the test sample solution was tested and analyzed, and the specific analysis results are shown in Tables 10 and 11, and Figure 5 and Figure 6 The results are shown in Table 10 and Figure 5 It is M 11 HPLC chromatogram and data analysis of the solution; Table 11 and Figure 6 It is M 21 HPLC chromatogram of the solution and explanation of the data analysis.
[0124] Table 10:
[0125] Serial number name Peak time (min) Separation 1 Impurity C 7.921 - 2 Impurity F 11.422 2.2 3 Impurity D 12.172 10.3 4 Impurity H 21.493 1.1 5 Impurity B 22.612 1.8 6 Impurity A & Desloratadine 24.370 2.6 7 Impurity E 26.582 3.6 8 Impurity G 34.809 16.5
[0126] From the above Table 10 and Figure 5 It can be seen that the impurity A of this detection method overlaps with the main peak of desloratadine, and the separation effect is poor.
[0127] Table 11:
[0128]
[0129] Table 12 below is a description of the liquid phase analysis results of the test solution and the main peak elution time.
[0130] Table 12:
[0131] Serial number name Peak time (min) Separation 1 Desloratadine 25.566 - 2 Unknown impurities 34.829 8.8
[0132] In summary, although the chromatographic conditions in the 2010 edition of the Chinese Pharmacopoeia can make each impurity peak, the peak of impurity A overlaps with the peak of the main peak, the peak response of the main peak is not high, and the separation degree between the peak of impurity E and the main peak is 1.4, which is not good.
[0133] Comparative Example 2
[0134] The preparation of each impurity solution in this comparative example is the same as that shown in Comparative Example 1 and Table 8.
[0135] The chromatographic conditions of the HPLC detection in this comparative example are as follows:
[0136] Chromatographic column: YMC J'sphere ODS-M80 4.6*150mm 4μm;
[0137] The elution method was isocratic elution;
[0138] Mobile phase: a mixture of buffer solution (methanol and acetonitrile stock solutions), and the volume ratio of buffer solution: (methanol and acetonitrile) is 70:30. The buffer solution is prepared by dissolving 1.8 g of sodium dodecyl sulfate in 800 ml, adding 200 ml of acetonitrile and then adding 1.0 ml of trifluoroacetic acid; in the methanol and acetonitrile stock solutions, the volume ratio of methanol to acetonitrile is 1:1 (500 ml of methanol and 500 ml of acetonitrile are prepared during preparation).
[0139] Column temperature: 35°C;
[0140] Detection wavelength: 280nm;
[0141] The injection volume was 10 μl;
[0142] Flow rate: 1.0 ml / min;
[0143] The test run time is 50min;
[0144] Test solution: 0.5 mg / ml;
[0145] The diluent is used for dilution with the mobile phase.
[0146] The solutions of each impurity and the desloratadine standard in Table 8 were respectively selected for detection and analysis to locate the peaks of each impurity (impurity A, impurity B, impurity C, impurity D, impurity E, impurity F, impurity G, impurity H), as shown in Table 13 below:
[0147] Table 13:
[0148]
[0149]
[0150] The same HPLC conditions for detecting each impurity in this comparative example were used to detect M 11 、M 21 , the test sample solution was tested and analyzed, and the specific analysis results are shown in Table 14 and Table 15, and Figure 7 and Figure 8 The results are shown in Table 14 and Figure 7 It is M 11 HPLC chromatogram and data analysis of the solution; Table 15 and Figure 8 It is M 21 HPLC chromatogram of the solution and explanation of the data analysis.
[0151] Table 14:
[0152] Serial number name Peak time (min) Separation 1 Impurity C 8.613 - 2 Impurity F 11.139 9.0 3 Impurity D 12.435 3.9 4 Impurity H 22.717 23.9 5 Impurity B 23.761 1.8 6 Impurity A & Impurity G 25.847 2.3 7 Desloratadine 26.618 0.76 8 Impurity E 29.431 3.6
[0153] From the above Table 14 and Figure 7 It can be seen that the impurity A of this detection method overlaps with the main peak of desloratadine, the impurity G peak coincides with the main peak, the main peak response is too low, and the separation effect is poor.
[0154] Table 15:
[0155]
[0156] From the above Table 15 and Figure 8 It can be seen that the impurity A in the spectrum overlaps with the main peak of desloratadine, the impurity G peak coincides with the main peak, the main peak response is too low, and the separation effect is poor.
[0157] From the data analysis results of the above-mentioned embodiments and comparative examples, it can be seen that the liquid phase detection method of the present invention can effectively separate the related substances in desloratadine with a high degree of separation, and the related substances such as impurity A do not overlap with the main peak, which has the advantage of high detection and analysis efficiency.
[0158] The specific embodiments described in the present invention are merely examples of the spirit of the present invention. Those skilled in the art may make various modifications or additions to the specific embodiments described or replace them in similar ways, but they will not deviate from the spirit of the present invention or exceed the scope defined by the attached claims.
[0159] Although the present invention has been described in detail and some specific embodiments have been cited, it is obvious to those skilled in the art that various changes and modifications can be made without departing from the spirit and scope of the present invention.
Claims
1. A method for analyzing and detecting related substances of desloratadine, wherein the method adopts high performance liquid chromatography for detection, and is characterized in that: The high performance liquid chromatography method comprises the following chromatographic conditions: The elution method was isocratic elution; Mobile phase: sodium dodecyl sulfate, sodium dihydrogen phosphate, triethylamine, acetonitrile, a mixture of methanol and water is used as the mobile phase, and phosphoric acid is used to adjust the pH value of the mobile phase to 2.8-3.3; 1.0g-1.1g sodium dodecyl sulfate and 0.86g-0.88g sodium dihydrogen phosphate are contained in each 550ml of water in the mobile phase; the volume ratio of water: triethylamine: acetonitrile: methanol in the mobile phase is 550: 1.4-1.6: 285-320: 145-156; Column temperature: 39℃~41℃; Detection wavelength: 280nm.
2. The method for analyzing and detecting related substances of desloratadine according to claim 1, characterized in that: The chromatographic column used in the high performance liquid chromatography method is a reverse pentafluoro chromatographic column.
3. The method for analyzing and detecting related substances of desloratadine according to claim 2, characterized in that: The reverse pentafluoro chromatographic column is a Shim-pack velox PFPP chromatographic column, which has a column length of 250 mm, an inner diameter of 4.6 mm, and a particle size of 5 μm.
4. The method for analyzing and detecting related substances of desloratadine according to claim 1, 2 or 3, characterized in that: The high performance liquid chromatography method also includes the following chromatographic conditions: The injection volume is 10μl~15μl; Flow rate: 1.0ml / min~1.2ml / min; The detection running time is 40min to 50min.
5. The method for analyzing and detecting related substances of desloratadine according to claim 4, characterized in that: The related substances of desloratadine include impurity A, impurity B, impurity C, impurity D, impurity E, impurity F, impurity G and impurity H; the structural formulas of the impurities of the related substances are as follows:
6. The method for analyzing and detecting related substances of desloratadine according to claim 5, characterized in that: The impurity A, impurity B, impurity C, impurity D, impurity E, impurity F, impurity G and impurity H can be separated from each other and produce peaks, and the degree of separation is greater than 1.5.