A method for determining the in vitro phosphate binding capacity of lanthanum carbonate chewable tablets

Abstract

This application provides a method for determining the in vitro phosphorus binding capacity of lanthanum carbonate chewable tablets, belonging to the field of mass spectrometry for separating substances into individual components for analytical testing. The method involves preparing a phosphate stock solution, pH medium, working linear standard solution, and test solution. ICP-MS is used to detect the working linear standard solution and the test solution, and the phosphorus binding capacity is calculated. Applying this method to the in vitro phosphorus binding capacity testing offers advantages such as simplicity, convenience, stability, high accuracy, and significantly improved sensitivity.

Description

Technical Field

[0001] This application relates to a method for determining the in vitro phosphorus binding force of lanthanum carbonate chewable tablets, belonging to the technical field of mass spectrometry for separating materials into individual components for analysis and testing. Background Technology

[0002] Lanthanum carbonate chewable tablets are phosphate binders. They were first approved in Japan in March 2009, and in 2004 they were approved by the US FDA for the treatment of hyperphosphatemia in patients with end-stage renal disease (ESRD). In October 2012, they were approved in China for the treatment of hyperphosphatemia in patients with chronic renal failure undergoing hemodialysis or continuous ambulatory peritoneal dialysis (CAPD).

[0003] Lanthanum carbonate is a topical gastrointestinal drug with very low oral absorption and bioavailability, making it unsuitable for evaluating bioequivalence using conventional in vivo pharmacokinetic endpoints. In vitro studies can be considered as an alternative method for efficacy evaluation. However, to ensure the safety and efficacy of the drug, a comprehensive assessment of its action is necessary; therefore, the study, detection, and monitoring of the phosphorus-binding capacity of lanthanum carbonate chewable tablets are crucial. Currently, there are no clear technical guidelines in my country for this purpose. Although various lanthanum-containing reagents have been used to evaluate phosphorus binding capacity, the results have been unsatisfactory. For example:

[0004] CN110664769A, CN111620363A, etc., use ultraviolet spectrophotometry to measure dissolution or phosphorus content as a quality standard. However, the method is cumbersome and requires the preparation of many solutions. Furthermore, phosphate is easily affected by pH and can be converted into hydrogen phosphate ions, dihydrogen phosphate ions, etc., which affects the accuracy of phosphorus content determination. In addition, solutions such as ascorbic acid are easily oxidized, which also affects the accuracy of the experiment.

[0005] CN113311100A and “Raghu Samy et al. Development and validation of an ionchromatography method for the determination of phosphate-binding of lanthanum carbonate” (Journal of Pharmaceutical and Biomedical Analysis 51(2010), p1108–1112) use ion chromatography to test the content of lanthanum or tocopheryl phosphate, but this method has low sensitivity and its limit of quantitation is 2 ppm. Summary of the Invention

[0006] In view of this, this application provides a method for determining the in vitro phosphorus binding capacity of lanthanum carbonate chewable tablets. The method is stable, highly accurate, and can greatly improve sensitivity.

[0007] Specifically, this application is implemented through the following scheme:

[0008] A method for determining the in vitro phosphorus binding capacity of lanthanum carbonate chewable tablets includes the following steps:

[0009] (1) Prepare a sodium phosphate stock solution of a certain concentration;

[0010] (2) Prepare media with pH 1.2, pH 3.0, and pH 5.0;

[0011] (3) Preparation of working linear solution: Take an appropriate amount of phosphorus standard solution, add pH medium and germanium standard solution, and dilute with nitric acid to prepare a series of standard solutions of different concentrations;

[0012] (4) Preparation of test solution: Take an appropriate amount of lanthanum carbonate chewable tablet sample, add pH medium and sodium phosphate stock solution, adjust the pH value, add germanium standard solution, and dilute with nitric acid to prepare test solutions of a series of concentrations.

[0013] (5) The working linear standard solution and the test solution were tested by ICP-MS and the phosphorus binding force was calculated.

[0014] Furthermore, as a preferred option:

[0015] In step (1), the concentration of sodium phosphate stock solution is 160–170 mg / mL.

[0016] In steps (3) and (4), the concentration of the phosphorus standard solution is 1000 μg / ml, the concentration of the germanium standard solution is 1000 μg / ml, and the concentration of nitric acid is 2%.

[0017] In step (3), the concentration range of the working linear solution is 0.2 μg / ml to 40 μg / ml.

[0018] In step (3), the working linear solution concentrations are 0.2 μg / mL, 0.3 μg / mL, 3 μg / mL, 15 μg / mL, 20 μg / mL, 30 μg / mL, and 40 μg / mL.

[0019] The concentration range of the test solution is 7.8–96 mmol / L. More preferably, the concentration range of the test solution is 7.8–9.6 mmol / L, 11.7–14.3 mmol / L, 15.6–19.1 mmol / L, 23.5–28.7 mmol / L, 31.3–38.2 mmol / L, 39.1–47.8 mmol / L, 62.6–76.4 mmol / L, and 78.2–95.6 mmol / L.

[0020] In step (4), the pH of the sample solutions of different concentrations were adjusted to pH 1.2, pH 3.0 and pH 5.0 respectively, and the pH was monitored during the process.

[0021] The parameters of the ICP-MS are as follows: gas flow rate of high-purity argon 1.05 L / min, collision gas and flow rate of high-purity helium 5.0 ml / min, nebulization chamber temperature 2℃, introduction speed 0.5 rps, introduction time 30 sec; stabilization time 40 sec, integration time of target phosphorus 0.3 s, integration time of internal standard germanium 0.12 s.

[0022] The in vitro phosphorus binding force is calculated as follows: Phosphorus binding force = (Initial sodium phosphate molar amount - Remaining sodium phosphate molar amount) / Initial sodium phosphate molar amount × 100%.

[0023] This invention proposes an analytical method for determining the in vitro phosphorus binding affinity of lanthanum carbonate chewable tablets using ICP-MS. This method is simple, convenient, stable, and highly accurate, and can greatly improve sensitivity, with a limit of quantitation of 0.2 ppm. Attached Figure Description

[0024] Figure 1 The phosphorus linear curve at pH 1.2 in Example 1;

[0025] Figure 2 The linear curve for phosphorus at pH 3.0 in Example 1;

[0026] Figure 3 The phosphorus linear curve is shown at pH 5.0 in Example 1. Detailed Implementation

[0027] The preferred embodiments of the present invention will be described below with reference to specific examples. It should be understood that the preferred embodiments described herein are for illustration and understanding only and are not intended to limit the present invention.

[0028] Example 1

[0029] This embodiment demonstrates the in vitro phosphorus binding assay of lanthanum carbonate chewable tablets. The specific steps are as follows:

[0030] (1) Preparation of sodium phosphate stock solution:

[0031] Weigh approximately 165g of sodium phosphate dodecahydrate, dissolve and dilute it to 1L with water, and mix well.

[0032] (2) Medium preparation:

[0033] ① pH 1.2 medium: Dilute 7.65 ml of hydrochloric acid with water to 1 L and mix well.

[0034] ② pH 3.0 medium: Take 0.14g of anhydrous sodium acetate and 5.9g of glacial acetic acid, dissolve and dilute with water to 1L, mix well, adjust the pH to 3.0 with hydrochloric acid, and mix well.

[0035] ③ pH 5.0 medium: Take 5g of sodium acetate trihydrate, dissolve and dilute it in water to 800ml, adjust the pH to 5.0 with glacial acetic acid, add 200ml of water and mix well.

[0036] (3) Preparation of test solution:

[0037] Take three portions of lanthanum carbonate chewable tablets, 48 ​​tablets in each portion, crush them, and place them separately in Erlenmeyer flasks. For the first portion, dissolve each tablet in 0.1 mol / L hydrochloric acid, add an appropriate amount of pH 1.2 medium to adjust to pH 1.2, wait at least 1 hour, monitor the pH, add phosphate stock solution, and adjust to pH 1.2. For the second portion, dissolve each tablet in 0.1 mol / L hydrochloric acid, add an appropriate amount of pH 3.0 medium to adjust to pH 3.0, wait at least 1 hour, monitor the pH, add phosphate stock solution, and adjust to pH 3.0 again. For the third portion, dissolve in 0.1 mol / L hydrochloric acid, add an appropriate amount of pH 5.0 medium and sodium acetate solution to adjust to pH 5.0, wait at least 1 hour, monitor the pH, add phosphate stock solution, and adjust to pH 5.0. The final reaction system for each portion is 250 ml. For each sample, eight sample solutions with final phosphate concentrations of 8.688, 13.03, 17.38, 26.06, 34.75, 43.44, 69.50, and 86.88 mmol / L were prepared, with six solutions for each concentration. The solutions were shaken at 37°C and 75 rpm for 24 hours. 5 ml of each of the above test solutions was taken, filtered, and 250 μl of the filtrate was placed in a 25 ml volumetric flask. 22.5 μl of internal standard germanium solution was added, and the solution was diluted to the mark with 2% nitric acid and mixed well.

[0038] (4) Preparation of working linear solution

[0039] ① Working linear solution - pH 1.2: Accurately measure 20 μl, 30 μl, 300 μl, 1.5 ml, 2 ml, 3 ml, and 4 ml of phosphorus standard solution (National Nonferrous Metals and Electronic Materials Analysis and Testing Center, 1000 μg / ml) into seven 100 ml volumetric flasks. Then add 1 ml of pH 1.2 medium and 90 μl of germanium standard solution (National Nonferrous Metals and Electronic Materials Analysis and Testing Center, 1000 μg / ml) to each flask. Dilute to the mark with 2% nitric acid and mix well to obtain working linear solutions of 0.2, 0.3, 3, 15, 20, 30, and 40 μg / ml.

[0040] ② Working linear solution - pH 3.0: Except that pH 3.0 is used instead of pH 1.2, the other preparation process is the same as that of working linear solution - pH 1.2, to obtain working linear solutions of 0.2, 0.3, 3, 15, 20, 30 and 40 μg / ml at pH 3.0.

[0041] ③ Working linear solution - pH 5.0: Except that pH 5.0 is used instead of pH 1.2, the other preparation process is the same as that of working linear solution - pH 1.2, to obtain working linear solutions of 0.2, 0.3, 3, 15, 20, 30 and 40 μg / ml at pH 5.0.

[0042] (5) Determination of phosphorus binding capacity:

[0043] The ICP-MS parameters were set as follows: high-purity argon gas flow rate 1.05 L / min, collision gas and high-purity helium flow rate 5.0 ml / min, nebulizer temperature 2℃, introduction speed 0.5 rps, introduction time 30 sec; stabilization time 40 sec, target phosphorus integration time 0.3 s, internal standard germanium integration time 0.12 s. The working linear solution and the test solution were analyzed separately to obtain... Figure 1 , Figure 2 , Figure 3 The results are shown in Tables 1 to 3.

[0044] Table 1: Results of phosphorus binding capacity determination at pH 1.2

[0045]

[0046] Table 2: Results of phosphorus binding capacity determination at pH 3.0

[0047]

[0048] Table 3: Results of phosphorus binding capacity determination at pH 5.0

[0049]

[0050]

[0051] in, Figure 1 The linear curve for phosphorus at pH 1.2 satisfies: y = 0.004547x + 2.472946E-004, R = 1.0000, BEC = 0.05439; Figure 2 The linear curve for phosphorus at pH 3.0 satisfies: y = 0.004751x + 3.757583E-005, R = 1.0000, BEC = 0.007909; Figure 3The linear curve for phosphorus at pH 5.0 satisfies: y = 0.004677x + 2.065995E-004, R = 1.0000, BEC = 0.04417.

[0052] Example 2

[0053] This embodiment conducts a sensitivity experiment, and the specific steps are as follows:

[0054] (1) Solution preparation:

[0055] ① Lower limit of quantitation solution - pH 1.2: Accurately measure 20 μl of phosphorus standard solution into a 100 ml volumetric flask, add 1 ml of pH 1.2 medium, add 90 μl of germanium standard solution, dilute to the mark with 2% nitric acid, and mix well. Prepare 6 portions using the same method.

[0056] ② Lower limit of quantitation solution - pH 3.0: Accurately measure 20 μl of phosphorus standard solution into a 100 ml volumetric flask, add 1 ml of pH 3.0 medium, add 90 μl of germanium standard solution, dilute to the mark with 2% nitric acid, and mix well. Prepare 6 portions using the same method.

[0057] ③ Lower limit of quantitation solution - pH 5.0: Accurately measure 20 μl of phosphorus standard solution into a 100 ml volumetric flask, add 1 ml of pH 5.0 medium, add 90 μl of germanium standard solution, dilute to the mark with 2% nitric acid, and mix well. Prepare 6 portions using the same method.

[0058] (2) Sensitivity test determination:

[0059] The ICP-MS parameters were set the same as in Example 1. The solutions with lower limits of quantitation and the working linear solution prepared in Example 1 were tested, and the results are shown in Table 4.

[0060] Table 4: Sensitivity Measurement Results at Various pH Values

[0061]

[0062]

[0063] The results show that the determination method provided in this case has good accuracy in the 0.2 μg / ml limit of quantification under pH 1.2, pH 3.0 and pH 5.0 media.

[0064] Example 3

[0065] This embodiment conducts accuracy and precision experiments, and the specific steps are as follows:

[0066] (1) Solution preparation:

[0067] 1) Blank excipient solutions: Accurately weigh approximately 1100 mg of blank excipient into three portions and place them in conical flasks. Add 200 ml of pH 1.2 medium, pH 3.0 medium, and pH 5.0 medium to each flask, shake (37℃, 75 rpm) for 24 h and incubate. Then remove the flasks to obtain blank excipient solution-pH 1.2, blank excipient solution-pH 3.0, and blank excipient solution-pH 5.0, respectively.

[0068] 2) Lower limit of quantitation control solution - pH 1.2: Accurately measure 2 ml of phosphorus standard solution into a 10 ml volumetric flask, dilute to the mark with blank excipient solution - pH 1.2, mix well, filter, take 100 μl of the filtrate, place it into a 100 ml volumetric flask, add 90 μl of germanium standard solution, dilute to the mark with 2% nitric acid, mix well, and you have obtained the solution (0.2 μg / ml). Prepare 6 portions using the same method.

[0069] 3) Lower limit of quantitation control solution - pH 3.0: Except that blank excipient solution - pH 3.0 is used instead of blank excipient solution - pH 1.2, the other preparation process is the same as that of the lower limit of quantitation control solution - pH 1.2. Prepare 6 portions (0.2 μg / ml) in the same way.

[0070] 4) Lower limit of quantitation control solution - pH 5.0: Except that blank excipient solution - pH 5.0 is used instead of blank excipient solution - pH 1.2, the other preparation process is the same as that of the lower limit of quantitation control solution - pH 1.2. Prepare 6 portions (0.2 μg / ml) in the same way.

[0071] 5) Low-concentration quality control solution - pH 1.2: Accurately measure 2 ml of phosphorus standard solution into a 10 ml volumetric flask, dilute to the mark with blank excipient solution - pH 1.2, mix well, filter, take 250 μl of the filtrate, place it into a 100 ml volumetric flask, add 90 μl of germanium standard solution, dilute to the mark with 2% nitric acid, mix well, and you have obtained the solution (0.5 μg / ml). Prepare 6 portions using the same method.

[0072] 6) Low-concentration quality control solution - pH 3.0: Except that blank excipient solution - pH 3.0 is used instead of blank excipient solution - pH 1.2, the preparation process is the same as that of low-concentration quality control solution - pH 1.2. (0.5 μg / ml) Prepare 6 portions in the same way.

[0073] 7) Low-concentration quality control solution - pH 5.0: Except that blank excipient solution - pH 5.0 is used instead of blank excipient solution - pH 1.2, the preparation process is the same as that of low-concentration quality control solution - pH 1.2. (0.5 μg / ml) Prepare 6 portions in the same way.

[0074] 8) Medium-concentration quality control solution - pH 1.2: Accurately measure 2 ml of phosphorus standard solution into a 10 ml volumetric flask, dilute to the mark with blank excipient solution - pH 1.2, mix well, filter, take 2 ml of the filtrate, place it into a 20 ml volumetric flask, add 18 μl of germanium standard solution, dilute to the mark with 2% nitric acid, mix well, and you have the solution. (20 μg / ml) Prepare 6 portions using the same method.

[0075] 9) Medium-concentration quality control solution - pH 3.0: Except that blank excipient solution - pH 3.0 is used instead of blank excipient solution - pH 1.2, the other preparation process is the same as that of medium-concentration quality control solution - pH 1.2. (20 μg / ml) Prepare 6 portions in the same way.

[0076] 10) Medium-concentration quality control solution - pH 5.0: Except that blank excipient solution - pH 5.0 is used instead of blank excipient solution - pH 1.2, the other preparation process is the same as that of medium-concentration quality control solution - pH 1.2. (20 μg / ml) Prepare 6 portions in the same way.

[0077] 11) High-concentration quality control solution - pH 1.2: Accurately measure 2 ml of phosphorus standard solution into a 10 ml volumetric flask, dilute to the mark with blank excipient solution - pH 1.2, filter, take 3 ml of the filtrate, place it into a 20 ml volumetric flask, add 18 μl of germanium standard solution, dilute to the mark with 2% nitric acid, mix well, and you have obtained the solution (30 μg / ml). Prepare 6 portions using the same method.

[0078] 12) High-concentration quality control solution - pH 3.0: Except that blank excipient solution - pH 3.0 is used instead of blank excipient solution - pH 1.2, the other preparation process is the same as that of high-concentration quality control solution - pH 1.2. Prepare 6 portions (30 μg / ml) in the same way.

[0079] 13) High-concentration quality control solution - pH 5.0: Except that blank excipient solution - pH 5.0 is used instead of blank excipient solution - pH 1.2, the other preparation process is the same as that of high-concentration quality control solution - pH 1.2. Prepare 6 portions (30 μg / ml) in the same way.

[0080] (2) Accuracy and precision experimental determination:

[0081] The ICP-MS parameters were set the same as in Example 1. The lower limit of quantitation solution, low concentration quality control solution, medium concentration quality control solution, high concentration quality control solution, and the working linear solution prepared in Example 1 were tested. The results are shown in Tables 5 to 7.

[0082] Table 5: Accuracy and precision experimental results at pH 1.2

[0083]

[0084] Table 6: Accuracy and Precision Experiment Results at pH 3.0

[0085]

[0086] Table 7. Accuracy and precision test results at pH 5.0

[0087]

[0088]

[0089] The results show that the present invention has good accuracy and precision in pH 1.2, pH 3.0, pH 5.0 media for its lower limit of quantitation quality control solution, low concentration quality control solution, medium concentration quality control solution, and high concentration quality control solution.

[0090] Example 4

[0091] This embodiment conducts a stability experiment on the solution, and the specific steps are as follows:

[0092] (1) Solution preparation:

[0093] ① Blank excipient solution: Accurately weigh three portions of blank excipient, each approximately 1100 mg, and place them in different conical flasks. Add 200 ml of pH 1.2 medium, pH 3.0 medium, and pH 5.0 medium to each flask, and incubate by shaking (37℃, 75 rpm) for 24 hours. Then remove the flasks.

[0094] ② Low-concentration quality control solution - pH 1.2: Accurately measure 2 ml of phosphorus standard solution into a 10 ml volumetric flask, dilute to the mark with blank excipient solution - pH 1.2, mix well, filter, take 250 μl of the filtrate, place it into a 100 ml volumetric flask, add 90 μl of germanium standard solution, dilute to the mark with 2% nitric acid, mix well, and you have obtained the solution (0.5 μg / ml). Prepare 6 portions using the same method, and measure them after standing at room temperature for 1, 2, and 7 days.

[0095] ③ Low concentration quality control solution - pH 3.0: Except that blank excipient solution - pH 3.0 is used instead of blank excipient solution - pH 1.2, the other preparation process is the same as low concentration quality control solution - pH 1.2. Prepare 6 portions (0.5 μg / ml) in the same way, and measure them after standing at room temperature for 1, 2 and 7 days.

[0096] ④ Low concentration quality control solution - pH 5.0: Except that blank excipient solution - pH 5.0 is used instead of blank excipient solution - pH 1.2, the other preparation process is the same as low concentration quality control solution - pH 1.2. Prepare 6 portions (0.5 μg / ml) in the same way, and measure them after standing at room temperature for 1, 2 and 7 days.

[0097] ⑤ High-concentration quality control solution - pH 1.2: Accurately measure 2 ml of phosphorus standard solution into a 10 ml volumetric flask, dilute to the mark with blank excipient solution - pH 1.2, filter, take 3 ml of the filtrate, place it into a 20 ml volumetric flask, add 18 μl of germanium standard solution, dilute to the mark with 2% nitric acid, mix well, and the solution is ready. (30 μg / ml) Prepare 6 portions using the same method, and measure at room temperature for 1, 2, and 7 days.

[0098] ⑥ High-concentration quality control solution - pH 3.0: Except that blank excipient solution - pH 3.0 is used instead of blank excipient solution - pH 1.2, the other preparation process is the same as that of low-concentration quality control solution - pH 1.2. Prepare 6 portions (30 μg / ml) in the same way, and measure them after standing at room temperature for 1, 2 and 7 days.

[0099] ⑦ High-concentration quality control solution - pH 5.0: Except that blank excipient solution - pH 5.0 is used instead of blank excipient solution - pH 1.2, the other preparation process is the same as that of low-concentration quality control solution - pH 1.2. Prepare 6 portions (30 μg / ml) in the same way, and measure them after standing at room temperature for 1, 2 and 7 days.

[0100] (2) Solution stability test:

[0101] The ICP-MS parameters were set the same as in Example 1. The low-concentration and high-concentration quality control solutions were tested on days 0, 1, 2, and 7, respectively, along with the working linear solution prepared in Example 1. The results are shown in Tables 7 to 9.

[0102] Table 7: Results of solution stability experiments at pH 1.2

[0103]

[0104]

[0105] Table 8: Results of solution stability experiments at pH 3.0

[0106]

[0107] Table 9: Results of solution stability experiments at pH 5.0

[0108]

[0109]

[0110] The results show that the assay method provided in this protocol has good stability in both low-concentration and high-concentration quality control solutions within 7 days under pH 1.2, pH 3.0, and pH 5.0 media.

[0111] It should be noted that the above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A method for determining the in vitro phosphate binding capacity of lanthanum carbonate chewable tablets, characterized in that, The steps are as follows: (1) Prepare a phosphate stock solution with a concentration of 160~170 mg / mL. The phosphate stock solution is obtained by dissolving sodium dodecahydrate in water. (2) Prepare pH media with pH values ​​of 1.2, 3.0, and 5.0 respectively; (3) Preparation of working linear solutions: Take phosphorus standard solution, add pH medium and germanium standard solution in sequence, and dilute with nitric acid to prepare a series of working linear solutions with different concentrations. The concentration of phosphorus standard solution is 1000µg / ml, the concentration of germanium standard solution is 1000µg / ml, and the concentration of nitric acid is 2%. (4) Preparation of test solution: Take lanthanum carbonate chewable tablet sample, add pH medium and phosphate stock solution, adjust pH value, add germanium standard solution, and dilute with nitric acid to prepare test solution of a series of concentrations. The concentration of germanium standard solution is 1000µg / ml, and the concentration of nitric acid is 2%. (5) The working linear standard solution and the test solution were tested by ICP-MS, and the phosphorus binding force was calculated using the following formula: Phosphorus binding = (initial moles of phosphate - remaining moles of phosphate) / initial moles of phosphate × 100%.

2. The method according to claim 1, wherein the method is for determining the in vitro phosphate binding capacity of a lanthanum carbonate chewable tablet. In step (2), the pH medium of pH 1.2 is obtained by diluting hydrochloric acid with water, the pH medium of pH 3.0 is obtained by diluting anhydrous sodium acetate and glacial acetic acid with water and adjusting the pH, and the pH medium of pH 5.0 is obtained by dissolving sodium acetate trihydrate in water and adjusting the pH.

3. The method for determining the in vitro phosphorus binding capacity of lanthanum carbonate chewable tablets according to claim 1, characterized in that: In step (3), the concentration range of the working linear solution is 0.2µg / ml to 40µg / ml.

4. The method for determining the in vitro phosphorus binding capacity of lanthanum carbonate chewable tablets according to claim 1, characterized in that: In step (3), the concentrations of the working linear solution series are 0.2µg / mL, 0.3µg / mL, 3µg / mL, 15µg / mL, 20µg / mL, 30µg / mL and 40µg / mL, respectively.

5. The method for determining the in vitro phosphorus binding capacity of lanthanum carbonate chewable tablets according to claim 1, characterized in that: In step (4), the concentration range of the test solution is 7.8~96 mmol / L.

6. The method for determining the in vitro phosphorus binding capacity of lanthanum carbonate chewable tablets according to claim 1, characterized in that: In step (4), the concentrations of the test solution are 7.8~9.6 mmol / L, 11.7~14.3 mmol / L, 15.6~19.1 mmol / L, 23.5~28.7 mmol / L, 31.3~38.2 mmol / L, 39.1~47.8 mmol / L, 62.6~76.4 mmol / L and 78.2~95.6 mmol / L.

7. The method for determining the in vitro phosphorus binding capacity of lanthanum carbonate chewable tablets according to claim 1, characterized in that: In step (4), the pH of the test solution is adjusted to 1.2, 3.0 and 5.0 respectively.

8. A method for determining the in vitro phosphorus binding affinity of lanthanum carbonate chewable tablets according to any one of claims 1-7, characterized in that, The parameters of the ICP-MS are as follows: gas flow rate of high-purity argon 1.05 L / min, collision gas and flow rate of high-purity helium 5.0 ml / min, nebulizer temperature 2℃, introduction speed 0.5 rps, introduction time 30 sec; stabilization time 40 sec, integration time of target phosphorus 0.3 s, integration time of internal standard germanium 0.12 s.

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