Method for measuring content of itopride hydrochloride in itopride hydrochloride tablet by HPLC (High Performance Liquid Chromatography)
Through the HPLC method, acetonitrile-0.01 mol/L ammonium dihydrogen phosphate solution was used as the mobile phase, combined with liquid chromatography and external standard method, the problem of coating affecting weighing in itopriligy tablets was solved, and the accurate detection of itopriligy hydrochloride was achieved, and the quality of the drug and the safety of the drug were improved.
Patent Information
- Application Number
- CN202510168760.1
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-02-14
- Publication Date
- 2025-07-04
AI Technical Summary
The prior art cannot effectively solve the problem of coating affecting weighing in itopriligy hydrochloride tablets, resulting in inaccurate content detection.
The content of ittopriligy hydrochloride was determined by liquid chromatography using acetonitrile-0.01 mol/L ammonium dihydrogen phosphate solution as the mobile phase, including sonication and filtration steps.
It realizes accurate detection of the content of itopriligy hydrochloride, has strong specificity, high sensitivity and good precision, ensuring the quality of the drug and the safety of clinical medicines.
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Figure CN120254092A_ABST
Abstract
Description
Technical Field
[0001] The present invention discloses a technology in the field of pharmaceutical detection, and relates to a method for determining the content of itopride hydrochloride in itopride hydrochloride tablets by HPLC. Background Art
[0002] Itopride hydrochloride is a new type of gastrointestinal motility-promoting drug, which is applicable to various symptoms caused by functional dyspepsia, such as upper abdominal discomfort, postprandial fullness, early satiety, loss of appetite, nausea, vomiting, etc. It was first successfully developed by Hokuriku Pharmaceutical Co., Ltd. in Japan, and the tablets were approved for marketing in Japan in 1995. Currently, the original research product (specification: 50 mg, trade name: Drug Approval Number: J20160075, manufacturer: ABBOTT LABORATORIES (M) SDN.BHD) has been imported into China, and 9 domestic companies have been approved to market generic drugs of this variety, with the specification of 50 mg for all.
[0003] Research shows that when detecting the content of itopride hydrochloride in the reference preparation of itopride hydrochloride tablets by the content method of itopride hydrochloride tablets in the second part of the Chinese Pharmacopoeia 2020 edition, the tablet coating cannot be completely ground, thus affecting weighing and further affecting the content detection of this product. There is also no good way to solve this problem at present. Summary of the Invention
[0004] In view of this, the present application provides a method for determining the content of itopride hydrochloride in itopride hydrochloride tablets by HPLC, which can detect the content of itopride hydrochloride.
[0005] According to one aspect of the present application, a method for determining the content of itopride hydrochloride in itopride hydrochloride tablets by HPLC is provided, including the following steps: Step 1: Prepare a blank solvent, and the blank solvent is acetonitrile - 0.01 mol / L ammonium dihydrogen phosphate solution; Step 2: Take an appropriate amount of itopride hydrochloride reference substance, weigh it accurately, and dilute it with the mobile phase to obtain a reference substance solution; Step 3: Take an appropriate amount of itopride hydrochloride tablets, place them in a volumetric flask, add hydrochloric acid solution, ultrasonically treat, cool to room temperature, dilute to the scale with hydrochloric acid solution, shake well, filter, accurately measure 2 ml of the continuous filtrate, place it in a volumetric flask, dilute to the scale with the mobile phase, and shake well to obtain; Step 4: Use liquid chromatography, obtain the chromatograms of the test solution and the reference substance solution under qualified chromatographic separation conditions, and determine the content of itopride hydrochloride by the external standard method.
[0006] According to one aspect of the present application, take an appropriate amount of itopride hydrochloride reference substance, weigh it accurately, dissolve it with the mobile phase and quantitatively dilute it to prepare a solution containing about 50 μg per 1 ml.
[0007] According to one aspect of the present application, take 10 tablets of itopride hydrochloride tablets, place them in a 200 ml volumetric flask, add 150 ml of 0.1 mol / L hydrochloric acid solution, ultrasonically treat for 30 minutes, let it cool, dilute to the mark with 0.1 mol / L hydrochloric acid solution, shake well, filter, accurately measure 2 ml of the continuous filtrate, place it in a 100 ml volumetric flask, dilute to the mark with the mobile phase, shake well, and you will get it.
[0008] According to one aspect of the present application, the mobile phase is acetonitrile - 0.01 mol / L ammonium dihydrogen phosphate solution.
[0009] According to one aspect of the present application, the ratio of acetonitrile to 0.01 mol / L ammonium dihydrogen phosphate solution is 1:5.
[0010] According to one aspect of the present application, the preparation of 0.01 mol / L ammonium dihydrogen phosphate solution is as follows: take 1.15 g of ammonium dihydrogen phosphate, add 1000 ml of water to dissolve it, and adjust the pH value to 3.0 with 3% phosphoric acid solution.
[0011] According to one aspect of the present application, the chromatographic conditions of liquid chromatography are as follows: the chromatographic column is octadecylsilane chemically bonded silica gel, and ammonium dihydrogen phosphate solution and acetonitrile are used as the mobile phase.
[0012] According to one aspect of the present application, the elution method is an isocratic elution method.
[0013] According to one aspect of the present application, the flow rate of the mobile phase for liquid chromatography detection is 0.8 - 1.2 ml / min, the column temperature is 25 - 35 °C, and the detection wavelength is 256 - 260 nm.
[0014] According to one aspect of the present application, the structural formula of itopride hydrochloride is:
[0015]
[0016] The beneficial effects of the present invention: Through step 1: Prepare a blank solvent, and the blank solvent is acetonitrile - 0.01 mol / L ammonium dihydrogen phosphate solution. Step 2: Take an appropriate amount of itopride hydrochloride reference substance, accurately weigh it, and dilute it with the mobile phase to obtain a reference substance solution; Step 3: Take an appropriate amount of itopride hydrochloride tablets, place them in a volumetric flask, add hydrochloric acid solution, ultrasonically treat, let it cool, dilute to the mark with hydrochloric acid solution, shake well, filter, accurately measure 2 ml of the continuous filtrate, place it in a volumetric flask, dilute to the mark with the mobile phase, shake well, and you will get it; Step 4: Use liquid chromatography, obtain the chromatograms of the test solution and the reference substance solution under qualified chromatographic separation conditions, and determine the content of itopride hydrochloride by the external standard method, which can detect the content of itopride hydrochloride, and has the advantages of strong specificity, high sensitivity, good precision, and high accuracy, ensuring the quality of itopride hydrochloride tablets and improving the safety of clinical medication. Description of the Drawings
[0017] Figure 1 Shows the structural formula of itopride hydrochloride;
[0018] Figure 2 Shows the full wavelength scan chart of itopride hydrochloride;
[0019] Figure 3 Shows the chromatogram of the reference solution in Example 1 of the present application;
[0020] Figure 4 Shows the chromatogram of the reference solution in Example 2 of the present application;
[0021] Figure 5 Shows the chromatogram of the reference solution in Example 3 of the present application;
[0022] Figure 6 Shows the chromatogram of the reference solution in Example 4 of the present application. Detailed implementation manners
[0023] The following embodiments are provided to better further understand the present invention, which is not limited to the described best implementation manners, and does not limit the content and protection scope of the present invention. Any product that is the same as or similar to the present invention obtained by anyone under the inspiration of the present invention or by combining the features of the present invention with those of other prior arts falls within the protection scope of the present invention.
[0024] For those embodiments where specific experimental steps or conditions are not indicated, the operations or conditions of the conventional experimental steps described in the literature in this field can be followed. For the reagents or instruments whose manufacturers are not indicated, they are all conventional reagent products that can be obtained through commercial purchase.
[0025] According to one aspect of the present application, a method for determining the content of itopride hydrochloride in itopride hydrochloride tablets by HPLC is provided, including the following steps: Step 1: Prepare a blank solvent, and the blank solvent is acetonitrile - 0.01 mol / L ammonium dihydrogen phosphate solution; Step 2: Take an appropriate amount of itopride hydrochloride reference substance, weigh it accurately, and dilute it with the mobile phase to prepare a reference solution; Step 3: Take an appropriate amount of itopride hydrochloride tablets, place them in a volumetric flask, add hydrochloric acid solution, ultrasonically treat, let it cool, dilute it to the mark with hydrochloric acid solution, shake well, filter, accurately measure 2 ml of the subsequent filtrate, place it in a volumetric flask, dilute it to the mark with the mobile phase, and shake well to obtain; Step 4: Use liquid chromatography, obtain the chromatograms of the test solution and the reference solution under qualified chromatographic separation conditions, and determine the content of itopride hydrochloride by the external standard method.
[0026] According to one aspect of Step 2 of the present application, take an appropriate amount of itopride hydrochloride reference substance, weigh it accurately, dissolve it with the mobile phase and quantitatively dilute it to prepare a solution containing about 50 μg per 1 ml.
[0027] According to one aspect of step 3 of the present application, take 10 tablets of itopride hydrochloride tablets, place them in a 200 ml volumetric flask, add 150 ml of 0.1 mol / L hydrochloric acid solution, ultrasonically treat for 30 minutes, let it cool, dilute to the mark with 0.1 mol / L hydrochloric acid solution, shake well, filter, accurately measure 2 ml of the continued filtrate, place it in a 100 ml volumetric flask, dilute to the mark with the mobile phase, shake well, and you will get it.
[0028] According to one aspect of step 2 and step 3 of the present application, the mobile phase is acetonitrile - 0.01 mol / L ammonium dihydrogen phosphate solution.
[0029] Preferably, the ratio of acetonitrile to 0.01 mol / L ammonium dihydrogen phosphate solution is 1:5.
[0030] According to one aspect of the present application, the preparation of 0.01 mol / L ammonium dihydrogen phosphate solution is as follows: Take 1.15 g of ammonium dihydrogen phosphate, add 1000 ml of water to dissolve it, and adjust the pH value to 3.0 with 3% phosphoric acid solution.
[0031] According to one aspect of the present application, preferably, the chromatographic conditions of the liquid chromatography method are as follows: The chromatographic column is octadecylsilane chemically bonded silica gel, and the mobile phase is ammonium dihydrogen phosphate solution and acetonitrile.
[0032] Preferably, the elution mode is an isocratic elution mode.
[0033] Preferably, the flow rate of the mobile phase for liquid chromatography detection is 0.8 - 1.2 ml / min, preferably 1.0 ml / min, the column temperature is 25 - 35 °C, preferably 30 °C, and the detection wavelength is 256 - 260 nm, preferably 258 nm.
[0034] According to one aspect of the present application, the structural formula of itopride hydrochloride is:
[0035]
[0036] Example 1
[0037] A detection method for determining the content of itopride hydrochloride in itopride hydrochloride tablets by HPLC, comprising the following steps:
[0038] Step 1: Prepare a blank solvent, and the blank solvent is acetonitrile - 0.01 mol / L ammonium dihydrogen phosphate solution;
[0039] Step 2: Prepare a reference solution (system suitability solution): The preparation of the reference solution (system suitability solution) is as follows: Take an appropriate amount of itopride hydrochloride reference substance, accurately weigh it, dissolve it with the mobile phase and quantitatively dilute it to make a solution containing about 50 μg per 1 ml (system suitability solution).
[0040] Step 3: Preparation of the test solution: Take 10 tablets of this product, place them in a 200 ml volumetric flask, add 150 ml of 0.1 mol / L hydrochloric acid solution, ultrasonically treat for 30 minutes, let it cool, dilute to the mark with 0.1 mol / L hydrochloric acid solution, shake well, filter, accurately measure 2 ml of the subsequent filtrate, place it in a 100 ml volumetric flask, dilute to the mark with the mobile phase, shake well, and you will get it.
[0041] Step 4: Use high performance liquid chromatography to obtain the chromatograms of the test solution and the reference solution under qualified chromatographic separation conditions, and determine the content of itopride hydrochloride by the external standard method.
[0042] The blank solvent described in the above Step 1 and Step 2 is acetonitrile - 0.01 mol / L ammonium dihydrogen phosphate solution (take 1.15 g of ammonium dihydrogen phosphate, add water to 1000 ml to dissolve it, adjust the pH value to 3.0 with 3% phosphoric acid solution) (1:5).
[0043] In the above Step 4, the chromatographic conditions for high performance liquid chromatography are as follows: The chromatographic column is octadecylsilane chemically bonded silica gel, and the mobile phase is acetonitrile - 0.01 mol / L ammonium dihydrogen phosphate solution (take 1.15 g of ammonium dihydrogen phosphate, add water to 1000 ml to dissolve it, adjust the pH value to 3.0 with 3% phosphoric acid solution) (1:5); the flow rate is 1.0 ml per minute; the column temperature is 30 °C; the detection wavelength is 258 nm; the injection volume is 20 μl.
[0044] The retention time of the itopride hydrochloride peak is 12.270 min, the number of theoretical plates is 13104, and the tailing factor is 1.64.
[0045] Example 2
[0046] A detection method for determining the content of itopride hydrochloride in itopride hydrochloride tablets by HPLC, comprising the following steps:
[0047] Step 1: Preparation of the blank solvent, and the blank solvent is acetonitrile - 0.01 mol / L ammonium dihydrogen phosphate solution;
[0048] Step 2: Preparation of the reference solution (system suitability solution): The preparation of the reference solution (system suitability solution) is as follows: Take an appropriate amount of itopride hydrochloride reference substance, accurately weigh it, dissolve it with the mobile phase and quantitatively dilute it to make a solution containing about 50 μg per 1 ml (system suitability solution).
[0049] Step 3: Preparation of the test solution: Take 10 tablets of this product, place them in a 200 ml volumetric flask, add 150 ml of 0.1 mol / L hydrochloric acid solution, ultrasonically treat for 30 minutes, let it cool, dilute to the mark with 0.1 mol / L hydrochloric acid solution, shake well, filter, accurately measure 2 ml of the subsequent filtrate, place it in a 100 ml volumetric flask, dilute to the mark with the mobile phase, shake well, and you will get it.
[0050] Step 4: Use high performance liquid chromatography (HPLC) to obtain the chromatograms of the test solution and the reference solution under qualified chromatographic separation conditions, and determine the content of itopride hydrochloride by the external standard method.
[0051] The blank solvent described in Steps 1 and 2 above is acetonitrile - 0.01 mol / L ammonium dihydrogen phosphate solution (dissolve 1.15 g of ammonium dihydrogen phosphate in 1000 ml of water, adjust the pH value to 3.0 with 3% phosphoric acid solution) (1:5).
[0052] In Step 4 above, the chromatographic conditions for HPLC are as follows: The chromatographic column is packed with octadecylsilane chemically bonded silica gel (Thermo gold AQ C18, 4.6 mm × 250 mm, 5 μm). The mobile phase is acetonitrile - 0.01 mol / L ammonium dihydrogen phosphate solution (dissolve 1.15 g of ammonium dihydrogen phosphate in 1000 ml of water, adjust the pH value to 3.0 with 3% phosphoric acid solution) (1:5). The flow rate is 1.0 ml per minute. The column temperature is 30 °C. The detection wavelength is 258 nm. The injection volume is 20 μl.
[0053] The retention time of the itopride hydrochloride peak is 12.270 min, the number of theoretical plates is 13104, and the tailing factor is 1.64.
[0054] Example 3
[0055] A detection method for determining the content of itopride hydrochloride in itopride hydrochloride tablets by HPLC, comprising the following steps:
[0056] Step 1: Prepare a blank solvent, and the blank solvent is acetonitrile - 0.01 mol / L ammonium dihydrogen phosphate solution;
[0057] Step 2: Prepare a reference solution (system suitability solution): The preparation of the reference solution (system suitability solution) is as follows: Weigh an appropriate amount of itopride hydrochloride reference substance accurately, dissolve it in the mobile phase and quantitatively dilute it to prepare a solution containing about 50 μg per 1 ml (system suitability solution).
[0058] Step 3: Prepare a test solution: Take 10 tablets of this product, place them in a 200 ml volumetric flask, add 150 ml of 0.1 mol / L hydrochloric acid solution, ultrasonically treat for 30 minutes, let it cool, dilute to the mark with 0.1 mol / L hydrochloric acid solution, shake well, filter, accurately measure 2 ml of the continued filtrate, place it in a 100 ml volumetric flask, dilute to the mark with the mobile phase, and shake well to obtain the test solution.
[0059] Step 4: Use high performance liquid chromatography (HPLC) to obtain the chromatograms of the test solution and the reference solution under qualified chromatographic separation conditions, and determine the content of itopride hydrochloride by the external standard method.
[0060] The blank solvent described in Steps 1 and 2 above is acetonitrile - 0.01 mol / L ammonium dihydrogen phosphate solution (take 1.15 g of ammonium dihydrogen phosphate, add 1000 ml of water to dissolve it, adjust the pH value to 3.0 with 3% phosphoric acid solution) (1:5).
[0061] In Step 4 above, the chromatographic conditions for liquid chromatography are as follows: The chromatographic column is packed with octadecylsilane chemically bonded silica gel (Agilent ZORBAX - C18, 4.6 mm × 250 mm, 5 μm), and acetonitrile - 0.01 mol / L ammonium dihydrogen phosphate solution (take 1.15 g of ammonium dihydrogen phosphate, add 1000 ml of water to dissolve it, adjust the pH value to 3.0 with 3% phosphoric acid solution) (1:5) is used as the mobile phase; the flow rate is 1.0 ml per minute; the column temperature is 30 °C; the detection wavelength is 258 nm; the injection volume is 20 μl.
[0062] The retention time of itopride hydrochloride peak is 12.270 min, the number of theoretical plates is 13104, and the tailing factor is 1.64.
[0063] Example 4
[0064] A detection method for determining the content of itopride hydrochloride in itopride hydrochloride tablets by HPLC, comprising the following steps:
[0065] Step 1: Prepare a blank solvent, and the blank solvent is acetonitrile - 0.01 mol / L ammonium dihydrogen phosphate solution;
[0066] Step 2: Prepare a reference solution (system suitability solution): The preparation of the reference solution (system suitability solution) is as follows: Take an appropriate amount of itopride hydrochloride reference substance, weigh it accurately, dissolve it with the mobile phase and quantitatively dilute it to a solution containing about 50 μg per 1 ml (system suitability solution).
[0067] Step 3: Prepare a test solution: Take 10 tablets of this product, place them in a 200 ml volumetric flask, add 150 ml of 0.1 mol / L hydrochloric acid solution, ultrasonically treat for 30 minutes, cool to room temperature, dilute to the mark with 0.1 mol / L hydrochloric acid solution, shake well, filter, accurately measure 2 ml of the subsequent filtrate, place it in a 100 ml volumetric flask, dilute to the mark with the mobile phase, and shake well to obtain the solution.
[0068] Step 4: Use liquid chromatography to obtain the chromatograms of the test solution and the reference solution under qualified chromatographic separation conditions, and determine the content of itopride hydrochloride by the external standard method.
[0069] The blank solvent described in Steps 1 and 2 above is acetonitrile - 0.01 mol / L ammonium dihydrogen phosphate solution (take 1.15 g of ammonium dihydrogen phosphate, add 1000 ml of water to dissolve it, adjust the pH value to 3.0 with 3% phosphoric acid solution) (1:5).
[0070] In the above step 4, the chromatographic conditions for liquid chromatography are as follows: the chromatographic column is packed with octadecylsilane-bonded silica gel (Waters Xbridge-C18, 4.6 mm × 250 mm, 5 μm), and the mobile phase is acetonitrile - 0.01 mol / L ammonium dihydrogen phosphate solution (dissolve 1.15 g of ammonium dihydrogen phosphate in 1000 ml of water, adjust the pH value to 3.0 with 3% phosphoric acid solution) (1:5); the flow rate is 1.0 ml per minute; the column temperature is 30 °C; the detection wavelength is 258 nm; the injection volume is 20 μl.
[0071] The retention time of itopride hydrochloride peak is 12.270 min, the number of theoretical plates is 13104, and the tailing factor is 1.64.
[0072] The detection method for determining the content of itopride hydrochloride in itopride hydrochloride tablets by HPLC according to this application can detect the content of itopride hydrochloride, and has the advantages of strong specificity, high sensitivity, good precision, high accuracy, etc., ensuring the quality of itopride hydrochloride tablets and improving the safety of clinical medication.
[0073] The above is only the preferred specific implementation manner of the present invention, but the protection scope of the present invention is not limited thereto. Any person skilled in the art within the scope disclosed by the present invention, according to the technical solution and its concept of the present invention, makes equivalent substitutions or changes, and should be covered by the protection scope of the present invention.
Claims
1. A method for determining the content of itopride hydrochloride in itopride hydrochloride tablets by HPLC, characterized in that, It includes the following steps: Step 1: Prepare a blank solvent, and the blank solvent is acetonitrile - 0.01 mol / L ammonium dihydrogen phosphate solution; Step 2: Take an appropriate amount of itopride hydrochloride reference substance, weigh it accurately, and dilute it with the mobile phase to obtain a reference substance solution; Step 3: Take an appropriate amount of itopride hydrochloride tablets, place them in a volumetric flask, add hydrochloric acid solution, ultrasonically treat, cool, dilute to the mark with hydrochloric acid solution, shake well, filter, accurately measure 2 ml of the subsequent filtrate, place it in a volumetric flask, and dilute to the mark with the mobile phase, shake well to obtain; Step 4: Use liquid chromatography to obtain the chromatograms of the test solution and the reference substance solution under qualified chromatographic separation conditions, and determine the content of itopride hydrochloride by the external standard method.
2. The method for determining the content of itopride hydrochloride in itopride hydrochloride tablets by HPLC according to claim 1, characterized in that, Take an appropriate amount of itopride hydrochloride reference substance, weigh it accurately, dissolve it with the mobile phase and quantitatively dilute it to make a solution containing about 50 μg per 1 ml.
3. The method for determining the content of itopride hydrochloride in itopride hydrochloride tablets by HPLC according to claim 1, characterized in that, Take 10 itopride hydrochloride tablets, place them in a 200 ml volumetric flask, add 150 ml of 0.1 mol / L hydrochloric acid solution, ultrasonically treat for 30 minutes, cool, dilute to the mark with 0.1 mol / L hydrochloric acid solution, shake well, filter, accurately measure 2 ml of the subsequent filtrate, place it in a 100 ml volumetric flask, and dilute to the mark with the mobile phase, shake well to obtain.
4. The method for determining the content of itopride hydrochloride in itopride hydrochloride tablets by HPLC according to claim 3, characterized in that, The mobile phase is acetonitrile - 0.01 mol / L ammonium dihydrogen phosphate solution.
5. The method for determining the content of itopride hydrochloride in itopride hydrochloride tablets by HPLC according to claim 4, characterized in that, The ratio of acetonitrile to 0.01 mol / L ammonium dihydrogen phosphate solution is 1:
5.
6. The method for determining the content of itopride hydrochloride in itopride hydrochloride tablets by HPLC according to claim 4, characterized in that, The preparation of 0.01 mol / L ammonium dihydrogen phosphate solution is as follows: Take 1.15 g of ammonium dihydrogen phosphate, add 1000 ml of water to dissolve it, and adjust the pH value to 3.0 with 3% phosphoric acid solution.
7. The method for determining the content of itopride hydrochloride in itopride hydrochloride tablets by HPLC according to any one of claims 1-6, characterized in that, The chromatographic conditions of liquid chromatography are as follows: The chromatographic column is octadecylsilane chemically bonded silica gel, and ammonium dihydrogen phosphate solution and acetonitrile are used as the mobile phase.
8. The method for determining the content of itopride hydrochloride in itopride hydrochloride tablets by HPLC according to claim 7, characterized in that, The elution mode is an isocratic elution mode.
9. The method for determining the content of itopride hydrochloride in itopride hydrochloride tablets by HPLC according to claim 7, characterized in that, The flow rate of the mobile phase for liquid chromatography detection is 0.8 - 1.2 ml / min, the column temperature is 25 - 35 °C, and the detection wavelength is 256 - 260 nm.
10. The method for determining the content of itopride hydrochloride in itopride hydrochloride tablets by HPLC according to claim 9, characterized in that, The structural formula of itopride hydrochloride is: