Method for determining impurities in fumaric acid Vonoprasan tablet by ICP-MS (Inductively Coupled Plasma Mass
The detection of impurities in fumarate vonora fumarate tablets through ICP-MS method solves the problem that it is difficult to effectively detect in the existing technology, realizes accurate detection of key impurities, and ensures the control of product quality.
Patent Information
- Application Number
- CN202510167784.5
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2025-02-14
- Publication Date
- 2025-06-27
AI Technical Summary
The prior art is difficult to effectively detect impurities in fumarate vonora fumarate tablets, which poses safety hazards and may endanger human health.
The method of determining impurities in fumarate vonola green tablets was used by ICP-MS. The corresponding standard solution and mixed standard solution were accurately measured and diluted, Au stock solution and nitric acid were added, and microwave digestion was performed. Then, the detection was performed using an inductively coupled plasma mass spectrometer.
It realizes accurate detection of elemental impurities such as vanadium, cobalt, nickel, arsenic, cadmium, lead, mercury and other elements in vonora fumarate tablets. It has high detection sensitivity and high accuracy, and can effectively control product quality.
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Abstract
Description
Technical Field
[0001] The present invention discloses a technology in the field of pharmaceutical detection, and relates to a method for determining impurities in vonoprazan fumarate tablets by ICP-MS method. Background Art
[0002] Vonoprazan fumarate tablets are potassium ion competitive acid blockers (P-CABs) developed by Takeda Pharmaceutical Company Limited, also known as proton pump inhibitors (hereinafter referred to as: PPIs). Existing PPIs such as lansoprazole are converted into active metabolites under acidic conditions, and this metabolite specifically inhibits the H+ / K+-ATPase of gastric mucosal parietal cells, thereby blocking the last step of gastric acid secretion. This product exerts its effect as a prototype drug without acid activation, mainly by competitively and reversibly binding to inhibit K+ and H+ / K+-ATPase, and can stay in gastric parietal cells for a long time, thereby rapidly inhibiting gastric acid secretion.
[0003] It was approved in Japan in December 2014 under the trade name Takecab, with specifications of 10 mg and 20 mg (calculated as C 17 H 16 FN3O2S). It was approved for marketing in China in December 2019, with the trade name: Walker, which is an original research imported preparation. It has become the first potassium ion competitive acid blocker approved to enter the Chinese market, providing a new option for clinical use in the treatment of reflux esophagitis, and will greatly improve the quality of life of patients with reflux esophagitis.
[0004] During the production process of vonoprazan fumarate tablets, impurities may affect the product quality. The potential impurities mainly come from raw and auxiliary materials, production equipment, packaging instruments, etc. Therefore, it is necessary to detect impurities to ensure the product quality of vonoprazan fumarate tablets, control the product quality, and avoid the impurity content involved exceeding the safety value, otherwise it will pose a safety hazard to patients taking vonoprazan fumarate tablets and endanger human health.
[0005] Currently, there is no good method to detect the impurities in vonoprazan fumarate tablets. Summary of the Invention
[0006] In view of this, the present application provides a method for determining impurities in vonoprazan fumarate tablets by ICP-MS. The impurities are vanadium, cobalt, nickel, arsenic, cadmium, lead and mercury, and the method includes the following steps: Step 1: Accurately measure appropriate amounts of mercury standard solution and mixed standard solutions of vanadium, cobalt, nickel, arsenic, cadmium and lead respectively, and dilute them with nitric acid aqueous solution to prepare mixed reference stock solutions containing each element; Step 2: Add Au stock solution respectively, and use 5% nitric acid aqueous solution to prepare linear solutions from the mixed reference stock solutions; Step 3: Accurately pipette appropriate amounts of mixed standard solutions of scandium, indium and bismuth elements, and dilute them with nitric acid aqueous solution to obtain internal standard solutions; Step 4: Weigh an appropriate amount of vonoprazan fumarate tablets, place them in a microwave digestion tube, add nitric acid and Au stock solution, digest them in a microwave digester, transfer the digested solution to a centrifuge tube, make up the volume with water, shake well and filter to obtain; Step 5: Use an inductively coupled plasma mass spectrometer to detect and analyze the metal impurities.
[0007] According to one aspect of the present application, accurately measure appropriate amounts of mercury standard solution and mixed standard solutions of vanadium, cobalt, nickel, arsenic, cadmium and lead respectively, and dilute them with nitric acid aqueous solution to prepare mixed reference stock solutions containing each element, and the concentration of the nitric acid aqueous solution is 5%.
[0008] According to one aspect of the present application, add Au stock solution respectively, and use 5% nitric acid aqueous solution to prepare linear solutions from the mixed reference stock solutions, and add 0.05 ml of Au stock solution, and the concentration gradients of the prepared linear solutions are 2 μg / L, 5 μg / L, 10 μg / L, 20 μg / L and 40 μg / L.
[0009] According to one aspect of the present application, accurately pipette appropriate amounts of mixed standard solutions of scandium, indium and bismuth elements, and dilute them with nitric acid aqueous solution to obtain internal standard solutions, and use 5% nitric acid aqueous solution to dilute to obtain an internal standard solution of 25 μg / L.
[0010] According to one aspect of the present application, weigh 0.1 g of vonoprazan fumarate tablets, place them in a microwave digestion tube, add 4 ml of nitric acid and 0.05 ml of Au stock solution, in a microwave digester, transfer the digested solution to a centrifuge tube, make up the volume with water to 50 ml, shake well and filter to obtain, and prepare two portions.
[0011] According to one aspect of the present application, the digestion temperature is 200 - 240 °C and the time is 30 - 50 min.
[0012] According to one aspect of the present application, the Au stock solution is obtained by accurately measuring an appropriate amount of Au standard solution and diluting it with 5% nitric acid aqueous solution to obtain a 10 mg / L Au stock solution.
[0013] According to one aspect of the present application, the conditions of the inductively coupled plasma mass spectrometer are as follows: RF power: 1400 - 1800 W, auxiliary gas flow rate: 1.0 - 1.5 L / min, plasma gas flow rate: 12 - 16 L / min, and nebulizer gas flow rate: 0.5 - 1.5 L / min.
[0014] According to one aspect of the present application, the detection mode of the inductively coupled plasma mass spectrometer is the He collision mode.
[0015] Advantages of the present invention: Through the following steps: Step 1: Accurately measure appropriate amounts of mercury standard solution and mixed standard solutions of vanadium, cobalt, nickel, arsenic, cadmium, and lead respectively, and dilute them with nitric acid aqueous solution to prepare mixed reference stock solutions containing each element; Step 2: Add Au stock solution respectively, and use nitric acid aqueous solution with a concentration of 5% to prepare linear solutions from the mixed reference stock solutions; Step 3: Accurately pipette appropriate amounts of mixed standard solutions of scandium, indium, and bismuth elements, and dilute them with nitric acid aqueous solution to obtain internal standard solutions; Step 4: Weigh an appropriate amount of voriconazole fumarate tablets, place them in a microwave digestion tube, add nitric acid and Au stock solution, digest them in a microwave digester, transfer the digested solution to a centrifuge tube, make up the volume with water, shake well and filter to obtain; Step 5: Use an inductively coupled plasma mass spectrometer to detect and analyze metal impurities, which can process the test samples of voriconazole fumarate tablets, completely dissolve and separate the voriconazole fumarate tablets, purify the existing impurities, clearly separate elemental impurities, and thus accurately detect the corresponding elemental impurity content with high detection sensitivity. At the same time, combined with an inductively coupled plasma mass spectrometer (ICP-MS), the detection parameters are limited to better detect the impurities in voriconazole fumarate tablets and better control the product quality with high detection accuracy. Description of the Drawings Detailed Embodiments
[0016] The following embodiments are provided to better further understand the present invention. They are not limited to the best embodiment, and do not limit the content and protection scope of the present invention. Any product identical 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 other prior art features falls within the protection scope of the present invention.
[0017] For those not specifying specific experimental steps or conditions in the embodiments, the operations or conditions of the conventional experimental steps described in the literature in the art can be followed. For the reagents or instruments not specifying the manufacturer, they are all conventional reagent products that can be obtained through commercial purchase.
[0018] According to one aspect of the present application, a method for determining impurities in voruprazan fumarate tablets by ICP-MS is provided. The impurities are vanadium, cobalt, nickel, arsenic, cadmium, lead, and mercury, and the method includes the following steps: Step 1: Accurately measure appropriate amounts of mercury standard solution and mixed standard solutions of vanadium, cobalt, nickel, arsenic, cadmium, and lead respectively, and dilute them with nitric acid aqueous solution to prepare mixed reference stock solutions containing each element; Step 2: Add Au stock solution respectively, and use 5% nitric acid aqueous solution to prepare linear solutions from the mixed reference stock solutions; Step 3: Accurately pipette an appropriate amount of mixed standard solution of scandium, indium, and bismuth elements, and dilute it with nitric acid aqueous solution to obtain an internal standard solution; Step 4: Weigh an appropriate amount of voruprazan fumarate tablets, place them in a microwave digestion tube, add nitric acid and Au stock solution, digest in a microwave digester, transfer the digested solution to a centrifuge tube, make up the volume with water, shake well and filter to obtain; Step 5: Use an inductively coupled plasma mass spectrometer for the detection and result analysis of metal impurities.
[0019] According to one aspect of Step 1 of the present application, accurately measure appropriate amounts of mercury standard solution and mixed standard solutions of vanadium, cobalt, nickel, arsenic, cadmium, and lead respectively, and dilute them with nitric acid aqueous solution to prepare mixed reference stock solutions containing each element, and the concentration of the nitric acid aqueous solution is 5%.
[0020] According to one aspect of Step 2 of the present application, add Au stock solution respectively, and use 5% nitric acid aqueous solution to prepare linear solutions from the mixed reference stock solutions, and add 0.05 ml of Au stock solution, and the concentration gradients of the prepared linear solutions are 2 μg / L, 5 μg / L, 10 μg / L, 20 μg / L, and 40 μg / L.
[0021] According to one aspect of Step 3 of the present application, accurately pipette an appropriate amount of mixed standard solution of scandium, indium, and bismuth elements, and dilute it with nitric acid aqueous solution to obtain an internal standard solution, and dilute it with 5% nitric acid aqueous solution to obtain an internal standard solution with a concentration of 25 μg / L.
[0022] According to one aspect of Step 4 of the present application, weigh 0.1 g of voruprazan fumarate tablets, place them in a microwave digestion tube, add 4 ml of nitric acid and 0.05 ml of Au stock solution, in a microwave digester, transfer the digested solution to a centrifuge tube, make up the volume with water to 50 ml, shake well and filter to obtain, and prepare two portions.
[0023] Preferably, the digestion temperature is 200 - 240 °C and the time is 30 - 50 min.
[0024] According to one aspect of the present application, it is characterized in that the Au stock solution is obtained by accurately measuring an appropriate amount of Au standard solution and diluting it with 5% nitric acid aqueous solution to obtain a 10 mg / L Au stock solution.
[0025] Preferably, the conditions of the inductively coupled plasma mass spectrometer are as follows: radio frequency power: 1400 - 1800 W, auxiliary gas flow: 1.0 - 1.5 L / min, plasma gas flow rate: 12 - 16 L / min, and nebulizer gas flow rate: 0.5 - 1.5 L / min.
[0026] According to one aspect of the present application, the detection mode of the inductively coupled plasma mass spectrometer is the He collision mode.
[0027] The present invention will be further described below in conjunction with embodiments. The described embodiments are only a part of the embodiments of the present invention, not all of the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts fall within the protection scope of the present invention.
[0028] Example 1: Detection of elemental impurities in vonoprazan fumarate tablets
[0029] 1. Instrumentation, reagents, reference substances, and test samples
[0030] 1.1 Instruments: Inductively coupled plasma mass spectrometry (ICP - MS), manufactured by PE, model NexIon1000G; electronic balance, manufactured by Mettler, model XSR204 / A; water purification instrument, manufactured by Elga, model Chorus1 + Chorus 2; microwave digestion instrument, manufactured by Milestone, model UltraWAVE;
[0031] 1.2 Reagents: Nitric acid, purity 65%, manufactured by CNW;
[0032] 1.3 Reference substances: Au standard solution, concentration 1000 mg / L, sourced from the National Analysis and Testing Center for Non - ferrous Metals and Electronic Materials; Hg standard solution, concentration 1000 mg / L, sourced from the National Analysis and Testing Center for Non - ferrous Metals and Electronic Materials; 28 - element (Cd Co Pb Tl V Ag As Ni Se Sb Li Cu Sn Ba Cr Zn Mo B Al Ti Mn W Ta Nb Rb Ge Sr Zr) mixed standard solution, concentration 100 mg / L, sourced from the National Analysis and Testing Center for Non - ferrous Metals and Electronic Materials; Be, Sc, Y, In, Tb, Bi standard solution, concentration 100 mg / L, sourced from the National Analysis and Testing Center for Non - ferrous Metals and Electronic Materials.
[0033] 1.4 Test samples: Vonoprazan fumarate tablets, specification 20 mg, manufactured by the Technical Center of Harbin Pharmaceutical Group.
[0034] 2. Detection conditions
[0035] Table 1 ICP - MS detection parameters
[0036]
[0037] 3. Solution Preparation
[0038] Step 1: Preparation of mixed reference stock solution: Accurately pipette appropriate amounts of mercury standard solution and mixed standard solutions of vanadium, cobalt, nickel, arsenic, cadmium, and lead respectively, and dilute them with 5% nitric acid aqueous solution to prepare a mixed reference stock solution containing 1.0 mg / L of each element per 1 ml;
[0039] Step 2: Linear solution: As shown in the following table, pipette appropriate amounts of the mixed reference stock solution, add 0.05 ml of Au stock solution respectively, and prepare linear solutions with 5% nitric acid aqueous solution;
[0040] Step 3: Internal standard solution: Accurately pipette appropriate amounts of the mixed standard solution of scandium, indium, and bismuth elements, and dilute it with 5% nitric acid aqueous solution to obtain an internal standard solution of 25 μg / L;
[0041] Step 4: Test sample solution: Weigh 0.1 g of the sample, place it in a microwave digestion tube, add 4 ml of nitric acid and 0.05 ml of Au stock solution, digest at 220 °C for 40 min in a microwave digester, transfer the digested solution to a centrifuge tube, make up the volume to 50 ml with water, shake well and filter to obtain (prepare 2 parallel portions);
[0042] Step 5: Use an inductively coupled plasma mass spectrometer for the detection and result analysis of metal impurities.
[0043] Among them, blank solution: Without adding the test sample, and the remaining preparation process is the same as that of the test sample solution; Au stock solution: Pipette appropriate amounts of Au standard solution, and dilute it with 5% nitric acid aqueous solution to obtain an Au stock solution of 10 mg / L.
[0044] Table 2 Preparation process of linear solution
[0045]
[0046] 4. Detection Results
[0047] Determination is carried out by ICP-MS inductively coupled plasma mass spectrometry: Take the blank solution, linear solution and test sample solution, inject samples for analysis in sequence, and calculate the impurity content of each element. The results are shown in the following table:
[0048] Table 3 Element impurity content in Voriconazole Fumarate Tablets
[0049]
[0050] The results show that: The content of impurities does not exceed the corresponding limit values, and each element impurity meets the quality control requirements. Therefore, the product quality control of the test sample Voriconazole Fumarate Tablets of the present invention is good.
[0051] Example 2: Methodological Verification
[0052] 1. Instrumentation, reagents, reference substances, and test samples
[0053] 1.1 Instruments: Inductively coupled plasma mass spectrometry (ICP-MS), manufactured by PE, model NexIon1000G; electronic balance, manufactured by Mettler, model XSR204 / A; water purification instrument, manufactured by Elga, model Chorus1 + Chorus 2; microwave digestion instrument, manufactured by Milestone, model UltraWAVE;
[0054] 1.2 Reagents: Nitric acid, purity 65%, manufactured by CNW;
[0055] 1.3 Reference substances: Au standard solution, concentration 1000 mg / L, sourced from the National Analysis and Testing Center for Nonferrous Metals and Electronic Materials; Hg standard solution, concentration 1000 mg / L, sourced from the National Analysis and Testing Center for Nonferrous Metals and Electronic Materials; 28-element (Cd Co Pb Tl V Ag As Ni Se Sb Li Cu Sn Ba Cr Zn Mo B Al Ti Mn W Ta Nb Rb Ge Sr Zr) mixed standard solution, concentration 100 mg / L, sourced from the National Analysis and Testing Center for Nonferrous Metals and Electronic Materials; Be, Sc, Y, In, Tb, Bi standard solution, concentration 100 mg / L, sourced from the National Analysis and Testing Center for Nonferrous Metals and Electronic Materials.
[0056] 1.4 Test samples: Voriconazole fumarate tablets, specification 20 mg, manufactured by the Technical Center of Harbin Pharmaceutical Group.
[0057] 2. The detection conditions are the same as in Example 1, as shown in Table 1.
[0058] 3. Specificity
[0059] 3.1 Solution preparation
[0060] ① Blank solution: The preparation method is the same as in Example 1.
[0061] ② Linear L1 solution: The preparation method is the same as in Example 1, as shown in Table 2.
[0062] 3.2 Detection results
[0063] Take the blank solution and the linear L1 solution, and perform injection analysis. The results are shown in the following table:
[0064] Table 4 Specificity results
[0065]
[0066] The results show that in the blank solution, the responses of the elements to be measured are all lower than those in the L1 (20% concentration level) solution, meeting the requirements.
[0067] 4. System Suitability
[0068] 4.1 Solution Preparation
[0069] ① QC solution: Use the linear solution L3 as the QC solution, as shown in Table 2.
[0070] 4.2 Test Results
[0071] Analyze the QC solution every time the injection does not exceed 10 times and at the end of the sequence, and calculate the drift value of the solution concentration. The results are shown in the following table.
[0072] Table 5 System Suitability Results
[0073]
[0074] The results show that the drift value of the QC solution concentration < 20%, meeting the requirements.
[0075] 5. Linearity
[0076] 5.1 Solution Preparation
[0077] ① Linear solution: Prepared in the same way as in Example 1, as shown in Table 2.
[0078] 5.2 Test Results
[0079] Take the blank solution and the linear solution, and calculate the calibration curve and the correlation coefficient by the instrument software. The results are shown in the following table:
[0080] Table 6 Linearity Results
[0081]
[0082] The results show that the linear correlation coefficients of the elements to be measured are all greater than 0.99, meeting the requirements.
[0083] 6. Accuracy
[0084] 6.1 Solution Preparation
[0085] ① Low-concentration spiked solution (50% limit level): Weigh 0.1 g of the sample, place it in a microwave digestion tube, add 4 ml of nitric acid and 0.05 ml of Au stock solution, then add 0.25 ml of the mixed reference substance stock solution, digest at 220 °C for 40 min in a microwave digester, transfer the digested solution to a centrifuge tube, make up the volume to 50 ml with water, shake well and filter to obtain (prepared in parallel for 3 portions).
[0086] ② Medium-concentration spiked solution (100% limit level): Weigh 0.1 g of the sample and place it in a microwave digestion tube. Add 4 ml of nitric acid and 0.05 ml of Au stock solution. Then add 0.50 ml of the mixed reference stock solution. Digest at 220 °C for 40 min in a microwave digester. Transfer the digested solution to a centrifuge tube, dilute to 50 ml with water, shake well and filter to obtain (prepare 3 replicates in parallel).
[0087] ③ Low-concentration spiked solution (150% limit level): Weigh 0.1 g of the sample and place it in a microwave digestion tube. Add 4 ml of nitric acid and 0.05 ml of Au stock solution. Then add 0.75 ml of the mixed reference stock solution. Digest at 220 °C for 40 min in a microwave digester. Transfer the digested solution to a centrifuge tube, dilute to 50 ml with water, shake well and filter to obtain (prepare 3 replicates in parallel).
[0088] 6.2 Test results
[0089] Analyze the accuracy solution and calculate the spike recovery rates at each limit level for each element. The results are shown in the following table:
[0090] Table 6 50% spike accuracy results
[0091]
[0092] Table 7 100% spike accuracy results
[0093]
[0094]
[0095] Table 8 150% spike accuracy results
[0096]
[0097]
[0098] The results show that the spike recovery rates of each element to be measured are all between 70% and 150%, meeting the requirements.
[0099] 7. Precision (repeatability and intermediate precision)
[0100] 7.1 Solution preparation
[0101] ① Repeatability: Weigh 0.1 g of the sample and place it in a microwave digestion tube. Add 4 ml of nitric acid and 0.05 ml of Au stock solution. Then add 0.50 ml of the mixed reference stock solution. Digest at 220 °C for 40 min in a microwave digester. Transfer the digested solution to a centrifuge tube, dilute to 50 ml with water, shake well and filter to obtain (prepare 6 replicates in parallel).
[0102] ②Intermediate precision solution: Independent preparation of linear solution and repeatability solution by different days and different experimenters.
[0103] 7.2 Test results
[0104] The repeatability and intermediate precision results are shown in the following table:
[0105] Table 9 Repeatability results (Analyst 1)
[0106]
[0107]
[0108] The results show that the repeatability RSD%(n = 6) of each element to be measured is less than 20%, meeting the requirements.
[0109] Table 10 Intermediate precision results (Analyst 2)
[0110]
[0111]
[0112] Table 11 Intermediate precision results (Analyst 1 & Analyst 2)
[0113]
[0114]
[0115] The results show that the intermediate precision RSD(n = 12) of each element to be measured is less than 25%, meeting the requirements.
[0116] 8. Quantitation limit and detection limit
[0117] 8.1 Solution preparation
[0118] ① Blank solution: Prepared in the same way as in Example 1 (prepared in parallel for 10 portions).
[0119] ② Quantitation limit solution: Pipette 0.1 ml of 7 - element stock solution (1 mg / L), add 0.05 ml of Au stock solution, and dilute to 50 ml with 5% nitric acid aqueous solution, mix well (prepared in parallel for 3 portions).
[0120] ③ Detection limit solution: Pipette 25 μl of 7 - element stock solution (1 mg / L), add 0.05 ml of Au stock solution, and dilute to 50 ml with 5% nitric acid aqueous solution, mix well (prepared in parallel for 3 portions).
[0121] 8.2 Test results
[0122] Based on the responses of 10 blank solutions, calculate the theoretical detection limit and quantification limit concentrations. Then prepare the quantification limit and detection limit solutions with corresponding concentrations and verify these two solutions. The results are shown in the following table:
[0123] Table 12 Results of Quantification Limit
[0124]
[0125]
[0126] Table 13 Results of Detection Limit
[0127]
[0128] The results show that: in the quantification limit solution, the recovery rates of the concentrations of each element to be measured are between 70% and 150%, meeting the requirements. The response values of each element in the detection limit solution are all higher than 3 times the response values of the elements in the blank solution, meeting the requirements.
[0129] The present invention can effectively detect 7 metal elements including vanadium, cobalt, nickel, arsenic, cadmium, lead, and mercury in voriconazole fumarate tablets, providing a simple, effective, and general detection method. This method uses microwave digestion for sample treatment, which can treat the test sample of voriconazole fumarate tablets, completely dissolve and separate the voriconazole fumarate tablets, purify the impurities, clearly separate the elemental impurities, so as to accurately detect the content of the corresponding elemental impurities with high detection sensitivity. At the same time, combined with an inductively coupled plasma mass spectrometer (ICP-MS) and defining the detection parameters, it can better detect the impurities in voriconazole fumarate tablets and better control the product quality with high detection accuracy.
[0130] The above is only a preferred specific embodiment 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 all should be covered within the protection scope of the present invention.
Claims
1. A method for determining impurities in vonoprazan fumarate tablets by ICP-MS, wherein the impurities are vanadium, cobalt, nickel, arsenic, cadmium, lead and mercury, characterized in that: The following steps are involved: Step 1: Accurately measure appropriate amounts of mercury standard solution and mixed standard solutions of vanadium, cobalt, nickel, arsenic, cadmium and lead, and dilute them with nitric acid aqueous solution to prepare mixed reference stock solutions containing each element; Step 2: Add Au stock solution separately and make the mixed reference stock solution into a linear solution with 5% nitric acid aqueous solution; Step 3: Accurately pipette an appropriate amount of the mixed standard solution of scandium, indium and bismuth elements, and dilute it with aqueous nitric acid to obtain an internal standard solution; Step 4: Weigh an appropriate amount of vonoplasm fumarate tablets, place them in a microwave digestion tube, add nitric acid and Au stock solution, digest them in a microwave digestion instrument, transfer the digested solution to a centrifuge tube, make up to volume with water, shake well and filter to obtain the solution; Step 5: Use inductively coupled plasma mass spectrometry to detect metal impurities and analyze the results.
2. The method for determining impurities in vonoprazan fumarate tablets by ICP-MS according to claim 1, characterized in that: Accurately measure appropriate amounts of mercury standard solution and mixed standard solutions of vanadium, cobalt, nickel, arsenic, cadmium and lead, and dilute them with aqueous nitric acid to prepare mixed reference stock solutions containing each element, and the concentration of the aqueous nitric acid is 5%.
3. The method for determining impurities in vonoprazan fumarate tablets by ICP-MS according to claim 2, characterized in that: Au stock solution was added separately, and the mixed reference stock solution was made into a linear solution with a 5% nitric acid aqueous solution, and 0.05 ml of Au stock solution was added to make a linear solution with a concentration gradient of 2 μg / L, 5 μg / L, 10 μg / L, 20 μg / L and 40 μg / L.
4. The method for determining impurities in vonoprazan fumarate tablets by ICP-MS according to claim 3, characterized in that: Accurately pipette an appropriate amount of the mixed standard solution of scandium, indium and bismuth elements, dilute it with aqueous nitric acid to obtain an internal standard solution, and dilute it with 5% aqueous nitric acid to obtain a 25 μg / L internal standard solution.
5. The method for determining impurities in vonoprazan fumarate tablets by ICP-MS according to claim 4, characterized in that: Weigh 0.1 g of vonoprazan fumarate tablets, place in a microwave digestion tube, add 4 ml of nitric acid and 0.05 ml of Au stock solution, transfer the digested solution to a centrifuge tube in a microwave digestion instrument, dilute to 50 ml with water, shake well and filter, and prepare two portions.
6. The method for determining impurities in vonoprazan fumarate tablets by ICP-MS according to claim 5, characterized in that: The decomposition temperature is 200-240°C and the decomposition time is 30-50 minutes.
7. The method for determining impurities in vonoprazan fumarate tablets by ICP-MS according to any one of claims 1 to 6, characterized in that: The Au stock solution is prepared by pipetting an appropriate amount of Au standard solution and diluting it with 5% nitric acid aqueous solution to obtain a 10 mg / L Au stock solution.
8. The method for determining impurities in vonoprazan fumarate tablets by ICP-MS according to claim 7, characterized in that: The conditions of the inductively coupled plasma mass spectrometer are: RF power: 1400-1800 W, auxiliary gas flow: 1.0-1.5 L / min, plasma gas flow rate: 12-16 L / min and nebulizer gas flow rate: 0.5-1.5L / min.
9. The method for determining impurities in vonoprazan fumarate tablets by ICP-MS according to claim 8, characterized in that: The detection mode of the inductively coupled plasma mass spectrometer is the He collision mode.