Method for determining content of tandospirone sustained release preparation

Abstract

The invention provides a method for determining the content of a tandospirone sustained release preparation. Wherein methanol is selected as an extraction solvent, so that a sample is prevented from being viscous, and effective extraction of the target component tandospirone is realized; a slice feeding method is adopted for direct extraction, and a conventional grinding and weighing method is not adopted, so that the problem of low detection result caused by serious adsorption after a test sample is ground is avoided; when the extraction is carried out by a tablet feeding method, glass beads are creatively added to assist the extraction, so that the sustained-release tablet can be rapidly disintegrated.

Description

Technical Field

[0001] The invention relates to the technical field of high performance liquid chromatography, in particular to a method for determining the content of a tandospirone sustained-release preparation. Background Art

[0002] The 2020 edition of the Chinese Pharmacopoeia records that the content of tandospirone citrate raw materials is determined by the perchloric acid titration method, and the content of tandospirone citrate capsules is determined by the liquid phase external standard method.

[0003] In the content determination of tandospirone citrate capsules,

[0004] The chromatographic conditions were as follows: octadecylsilane bonded silica gel was used as filler; 0.01 mol / L potassium dihydrogen phosphate solution (pH adjusted to 7.5 with 10% sodium hydroxide solution)-acetonitrile (60:40) was used as mobile phase; detection wavelength was 243 nm; injection volume was 20 μl;

[0005] Preparation method of test solution: Take 10 capsules of this product, transfer the contents to a 25 ml volumetric flask with an appropriate amount of mobile phase, wash the capsule shell with mobile phase in batches, combine the washing solution into the same volumetric flask, add an appropriate amount of mobile phase, shake to dissolve, dilute to the scale with mobile phase, shake well, filter, accurately measure an appropriate amount of filtrate, and dilute with mobile phase to make a solution containing about 40 μg per 1 ml.

[0006] The tandospirone citrate sustained-release preparation reported in the prior art usually contains a hydrophilic gel material, which is characterized by swelling after contacting water or gastric juice to form a gel barrier, thereby controlling the release rate of the drug. However, when the tandospirone sustained-release preparation in the above patent was assayed using the assay method recorded in the Chinese Pharmacopoeia, the inventors found that during the assay or pre-treatment process, the sample containing the hydrophilic gel became viscous due to the use of an aqueous solvent (mobile phase solution), making it difficult to centrifuge or filter it, thereby making it impossible to perform subsequent extraction operations and assay processing. Summary of the invention

[0007] In order to improve the above technical problems, the present invention provides a method for determining the content of a tandospirone sustained-release preparation, the method comprising the following steps:

[0008] 1) Preparation of test solution: Take the tandospirone sustained-release preparation, add an appropriate amount of solvent to disintegrate the sustained-release preparation, make up to volume, and centrifuge to obtain the supernatant;

[0009] 2) Content determination: Determine the content of tandospirone in the supernatant.

[0010] In some embodiments, in step 1), the test solution is prepared by taking the tandospirone sustained-release preparation, adding an appropriate amount of solvent to disintegrate the sustained-release preparation without grinding, fixing the volume, and centrifuging to obtain a supernatant.

[0011] In some embodiments, in step 1), the tandospirone sustained-release preparation is taken without grinding, weighed and placed in a container, an appropriate amount of solvent is added to disintegrate the sustained-release preparation, the solvent is continued to be added to the fixed volume, the mixture is shaken, and the supernatant is obtained by centrifugation.

[0012] In some embodiments, the solvent used in step 1) is methanol.

[0013] In some embodiments, in step 1), grinding beads, such as glass beads, steel beads, ceramic beads, zirconia beads, etc., are pre-added in the container.

[0014] According to an embodiment of the present invention, the tandospirone sustained-release preparation comprises tandospirone or a pharmaceutically acceptable salt thereof.

[0015] In some embodiments, the tandospirone sustained-release formulation comprises a hydrophilic gel material.

[0016] In some embodiments, the hydrophilic gel material refers to a hydrophilic polymer that swells when exposed to water or digestive fluid to form a gel barrier to control drug dissolution.

[0017] In some embodiments, the hydrophilic gel material is selected from natural gums (eg, sodium alginate, agar, tragacanth), cellulose derivatives, and polyethylene oxide.

[0018] In some embodiments, the hydrophilic gel material is selected from at least one of methyl cellulose (MC), hydroxymethyl cellulose, sodium hydroxymethyl cellulose (CMC-Na), hydroxyethyl cellulose (HEC), hydroxypropyl cellulose, hydroxypropyl methyl cellulose (HPMC), carboxymethyl cellulose, carboxyethyl cellulose, microcrystalline cellulose, povidone (PVP), sodium alginate, carbomer, Kollidon SR, and polyethylene oxide.

[0019] In some embodiments, the HPMC is selected from at least one of HPMC A4M, HPMC E4M, HPMC E10M, HPMC K4M, HPMC K15M, HPMC K50M, and HPMC K100M.

[0020] In some embodiments, the polyethylene oxide is selected from one or more of polyethylene oxide WSR and polyethylene oxide N-80.

[0021] In some embodiments, the polyethylene oxide is selected from one or more of polyethylene oxide WSR 303, polyethylene oxide WSR 1105, polyethylene oxide WSR301, polyethylene oxide WSR 205, and polyethylene oxide N-80.

[0022] In some embodiments, the pharmaceutically acceptable salt is hydrochloride, sulfate, tartrate, oxalate, maleate, fumarate, citrate, methanesulfonate, p-toluenesulfonate, nitrate; preferably hydrochloride or citrate; more preferably citrate.

[0023] In some embodiments, the tandospirone sustained-release preparations include tandospirone sustained-release tablets, tandospirone sustained-release pills, and tandospirone sustained-release capsules.

[0024] In some embodiments, the tandospirone sustained-release capsules need to remove the capsule shell before content determination.

[0025] In some embodiments, in step 1), the concentration of tandospirone citrate in the test solution is 0.05 mg / mL-5.0 mg / mL, preferably 0.1 mg / mL-2.0 mg / mL, more preferably 0.2 mg / mL-1.0 mg / mL, for example 0.6 mg / mL.

[0026] In some embodiments, in step 1), the concentration of the hydrophilic gel material in the test solution is 0.1 mg / mL-10.0 mg / mL, preferably 0.5 mg / mL-5.0 mg / mL, more preferably 1.0 mg / mL-3.0 mg / mL, for example 2.2 mg / mL.

[0027] In some embodiments, in step 1), 5 tandospirone sustained-release tablets are taken, and the capacity of the container is 250 mL.

[0028] In some embodiments, in step 1), the mass ratio of the amount of grinding beads to tandospirone citrate is 1-20 beads: 50-200 mg, for example, 10 beads: 150 mg.

[0029] In some embodiments, in step 1), the mass ratio of the amount of grinding beads to the hydrophilic gel material is 1-20 beads: 200-1000 mg, for example, 10 beads: 550 mg.

[0030] In some embodiments, in step 1), ultrasound, vortexing, shaking, etc. can be used to promote the dissolution and disintegration of the sample.

[0031] In some embodiments, in step 1), the diameter of the grinding beads is 3-8 mm, preferably 6-8 mm.

[0032] In some embodiments, step 1) specifically includes the following steps: take 5 tandospirone sustained-release tablets, accurately weigh them, place them in a 250 mL volumetric bottle pre-added with grinding beads, add an appropriate amount of solvent to disintegrate the sustained-release preparation, continue to add solvent to dilute to the scale of the volumetric bottle, shake well, and centrifuge to obtain the test solution.

[0033] In some embodiments, step 1) further comprises a dilution step of the test solution:

[0034] Take a certain amount of the test solution in step 1) into a volumetric flask, add an appropriate amount of solvent to further dissolve it, then dilute it to the scale of the volumetric flask with the mobile phase, shake well, and filter to obtain the diluted test solution.

[0035] In some embodiments, the solvent used for dissolution is methanol.

[0036] In some embodiments, the ratio of the volume of the test solution to the volume of the solvent is 1:1.

[0037] In some embodiments, the concentration of tandospirone citrate in the diluted test solution is 0.005 mg / mL-1.0 mg / mL, preferably 0.01 mg / mL-0.10 mg / mL, and more preferably 0.03 mg / mL.

[0038] In some embodiments, the concentration of the hydrophilic gel material in the diluted test solution is 0.01 mg / mL-2.0 mg / mL, preferably 0.05 mg / mL-0.5 mg / mL, and more preferably 0.11 mg / mL.

[0039] In some embodiments, in the dilution step of the test solution, the mobile phase used for dilution includes phase A and phase B; phase A is 0.005 mol / L-0.2 mol / L (e.g., 0.025 mol / L) potassium dihydrogen phosphate aqueous solution, and phase B is acetonitrile.

[0040] In some embodiments, phase A:phase B=60:40.

[0041] In some embodiments, phase A is further adjusted to pH 7.5 using 20% ​​sodium hydroxide solution.

[0042] In some embodiments, step 1) further comprises a dilution step of the test solution:

[0043] Take 5 mL of the test solution in step 1) into a 100 mL volumetric flask, add 5 mL of solvent to further dissolve, then dilute to the scale of the volumetric flask with the mobile phase, shake well, and filter to obtain the diluted test solution.

[0044] In some embodiments, high performance liquid chromatography is used to determine the content in step 2).

[0045] In some embodiments, in step 2), the content is calculated by peak area using an external standard method.

[0046] In some embodiments, in step 2), the chromatogram is recorded to about 1.3 times the retention time of the main component peak.

[0047] In some embodiments, the chromatographic conditions for content determination in step 2) are:

[0048] Chromatographic column: octadecylsilane bonded silica gel is used as filler, such as C18; preferably, the size of the chromatographic column is 4.6 mm × 150 mm, 5 μm;

[0049] The mobile phase conditions are: phase A is 0.005 mol / L-0.2 mol / L (e.g. 0.025 mol / L) potassium dihydrogen phosphate aqueous solution, phase B is acetonitrile; isocratic elution;

[0050] The detection wavelength is 240nm-246nm, for example 243nm;

[0051] The column temperature is 20°C-40°C, for example 30°C;

[0052] Injection volume 5μl-50μl, for example 20μl;

[0053] The flow rate is 0.8-1.2ml / min.

[0054] In some embodiments, phase A:phase B=60:40.

[0055] In some embodiments, phase A is further adjusted to pH 7.5 using 20% ​​sodium hydroxide solution.

[0056] In some embodiments, the content determination method further comprises the following steps:

[0057] 3) Preparation of reference substance solution: accurately weigh the reference substance, place it in a container, add a solvent to dissolve the reference substance, and make up the volume; the reference substance is tandospirone or a pharmaceutically acceptable salt thereof.

[0058] In some embodiments, the solvent used in step 3) is methanol.

[0059] In some embodiments, in step 3), grinding beads, such as glass beads, steel beads, ceramic beads, zirconia beads, etc., are pre-added in the container.

[0060] In some embodiments, in step 3), the concentration of the reference solution is 0.2 mg / mL-0.4 mg / mL, for example 0.3 mg / mL.

[0061] In some embodiments, in step 3), the mass ratio of the amount of grinding beads to tandospirone citrate is 1-10 beads: 10-100 mg, for example, 4 beads: 30 mg.

[0062] In some embodiments, in step 3), the diameter of the grinding beads is 3-8 mm, preferably 6-8 mm.

[0063] In some embodiments, step 3) specifically includes the following steps: accurately weigh 30 mg of a reference substance, place it in a 100 mL volumetric flask pre-added with grinding beads, add a solvent to dissolve the reference substance, and then dilute it with a solvent to the volume of the volumetric flask; the reference substance is tandospirone or a pharmaceutically acceptable salt thereof.

[0064] In some embodiments, step 3) further comprises a dilution step of the reference solution:

[0065] Take a certain amount of the reference substance solution in step 3) into a volumetric flask, dilute it to the scale of the volumetric flask with the mobile phase, shake well, and filter to obtain the diluted reference substance solution.

[0066] In some embodiments, in the dilution step of the reference solution, the mobile phase used for dilution includes phase A and phase B; phase A is 0.005 mol / L-0.2 mol / L (eg, 0.025 mol / L) potassium dihydrogen phosphate aqueous solution, and phase B is acetonitrile.

[0067] In some embodiments, phase A:phase B=60:40.

[0068] In some embodiments, phase A is further adjusted to pH 7.5 using 20% ​​sodium hydroxide solution.

[0069] In some embodiments, the concentration of the diluted reference solution is 0.005 mg / mL-1.0 mg / mL, preferably 0.01 mg / mL-0.10 mg / mL, more preferably 0.02 mg / mL-0.04 mg / mL, for example 0.03 mg / mL.

[0070] In some embodiments, the tandospirone sustained-release preparation optionally further comprises a filler, a bleaching aid, a lubricant, and a binder.

[0071] In some embodiments, in the tandospirone sustained-release preparation, the content of the active pharmaceutical ingredient is 1-15% (preferably 2.5-10%), and the content of the hydrophilic gel material is 5-75% (preferably 15-65%, and further preferably 15-61.7%).

[0072] In some embodiments, the tandospirone sustained-release formulation includes the following components in weight percentage:

[0073]

[0074] In some embodiments, the filler is selected from one or a combination of lactose, sucrose, microcrystalline cellulose, pregelatinized starch, mannitol, sorbitol, xylitol, glucose, calcium sulfate, calcium hydrogen phosphate, calcium phosphate, calcium chloride, aluminum chloride, sodium chloride, calcium oxide, zinc oxide, and magnesium oxide; preferably microcrystalline cellulose.

[0075] In some embodiments, the bleaching aid is selected from one or a combination of sodium carbonate, sodium bicarbonate, potassium bicarbonate, magnesium carbonate, and calcium carbonate; preferably, the bleaching aid is selected from sodium carbonate and / or sodium bicarbonate.

[0076] In some embodiments, the lubricant is selected from one or a combination of talc, micro-powdered silica, magnesium stearate, calcium stearate, zinc stearate, sodium stearyl fumarate, magnesium lauryl sulfate, sodium lauryl sulfate, and hydrogenated vegetable oil; preferably magnesium stearate.

[0077] In some embodiments, the binder is selected from one or a combination of polyvinyl pyrrolidone, gelatin, xanthan gum, dextrin, polyvinyl alcohol, and carboxymethyl cellulose; preferably, the binder is selected from polyvinyl pyrrolidone and / or polyvinyl alcohol.

[0078] Beneficial Effects

[0079] The method for determining the content of the above-mentioned tandospirone sustained-release preparation provided by the present invention has the following advantages:

[0080] 1. Methanol was selected as the extraction solvent to avoid sample viscosity and achieve effective extraction of the target component tandospirone citrate;

[0081] 2. The extraction is directly carried out by the chip casting method instead of the conventional grinding and weighing method, which avoids the problem of low test results caused by severe adsorption of the test sample after grinding;

[0082] 3. When extracting by the tablet method, grinding beads are creatively added to assist the extraction, so that the sustained-release tablets can disintegrate quickly. BRIEF DESCRIPTION OF THE DRAWINGS

[0083] Figure 1 This is a typical picture of the reference solution.

[0084] Figure 2 A typical graph of the test solution. DETAILED DESCRIPTION

[0085] The technical scheme of the present invention will be further described in detail below in conjunction with specific embodiments. It should be understood that the following embodiments are only exemplary descriptions and explanations of the present invention and should not be construed as limiting the scope of protection of the present invention. All technologies implemented based on the above content of the present invention are included in the scope that the present invention is intended to protect.

[0086] Unless otherwise specified, the raw materials and reagents used in the following examples are commercially available or can be prepared by known methods.

[0087] The tandospirone sustained-release preparation and its preparation process refer to Example 8 in patent CN113018271B.

[0088] Example 1 Optimization of extraction solvent

[0089] Because the sustained-release preparation contains a hydrophilic gel material - polyethylene oxide, when a conventional aqueous solvent (aqueous buffer solution) is used to extract the sample, the sample becomes extremely viscous after swelling and cannot be post-processed by centrifugation or filtration. This application compares the swelling of the sustained-release preparation in common solvents such as water, methanol, acetonitrile, isopropanol, and N,N-dimethylformamide.

[0090] Table 1 Comparison of swelling of sustained-release preparations in different solvents

[0091]

[0092] White powder # It is an excipient that is insoluble in methanol and does not contain the active ingredient tandospirone or a pharmaceutically acceptable salt thereof.

[0093] The results in Table 1 show that even when organic solvents such as acetonitrile, isopropanol, and N,N-dimethylformamide are used as extraction solvents, the solution of the sustained-release preparation still contains some floccules and the solution is viscous; when methanol is used as the extraction solvent, the solution of the sustained-release preparation is clear and non-viscous, which effectively solves the problems of sample viscosity, floccules, and difficulty in post-processing, thereby ensuring the complete extraction of the main drug.

[0094] Example 2 Effect of glass beads on disintegration

[0095] When measuring by the tablet method, the inventors found that even if methanol was selected as the extraction solvent, the sustained-release preparation was difficult to completely disintegrate or disintegrated slowly in methanol, resulting in a longer time required for complete extraction and a longer measurement time. Therefore, grinding beads - glass beads were added to assist.

[0096] Table 2 Disintegration of sustained-release preparations under different treatment methods

[0097]

[0098]

[0099] The results are shown in Table 2. The addition of glass beads can significantly increase the disintegration rate of the tandospirone sustained-release preparation.

[0100] Example 3 Study on the Slicing Method and the Grinding Method

[0101] Tablet method: Take 5 tandospirone sustained-release tablets, place them in a 250ml volumetric bottle, add 10 glass beads with a diameter of about 7-8mm, add about 20ml of methanol, shake to disintegrate, then add methanol for vortex extraction. After dilution, measure the content.

[0102] Grinding method: Take 20 tandospirone sustained-release tablets, grind them in an agate mortar and mix them evenly, take 600 mg of fine powder, weigh it accurately, put it in a 250 ml volumetric bottle, add about 150 ml of methanol and shake it, let it stand at room temperature, and then vortex extract it. After dilution, determine the content.

[0103] Table 3 Content determination under the tableting method and grinding method

[0104]

[0105]

[0106] The results show that the results of the slice method are basically consistent with the theoretical value, and the method has good repeatability; the results of the grinding method are obviously lower, and the slice method used for this product is significantly better than the grinding method.

[0107] The present invention adopts the tableting method in the sample preparation process, uses methanol as the solvent, and adds glass beads to assist in disintegration, thereby solving the problem that the sustained-release preparation is not easy to disintegrate, and the obtained solution is non-viscous, so that the test solution can be post-processed by centrifugation or filtration, thereby shortening the sample pre-processing time.

[0108] The content determination result of the tablet method of the present invention is more accurate than that of the conventional grinding method. The content determination result of the conventional grinding method is 3% lower than that of the tablet method of the present invention. The present invention creatively solves the problem of low determination results caused by adsorption of the main drug after grinding.

[0109] Example 4 Content Determination

[0110] Take 5 tablets of tandospirone sustained-release tablets for the test solution, weigh them accurately, put them in a 250ml volumetric flask pre-added with 10 glass beads with a diameter of about 7-8mm, add about 20ml of methanol, shake to disintegrate, add about 180ml of methanol, vortex for 5 minutes, dilute to the scale with methanol, shake well, centrifuge at 4000 revolutions per minute for 3 minutes, accurately measure 5ml of the supernatant, put it in a 100ml volumetric flask, accurately add 5ml of methanol, add the mobile phase to dilute to the scale, shake well, filter, and take the filtrate.

[0111] Reference solution: Weigh 30 mg of tandospirone citrate reference substance accurately, place it in a 100 ml volumetric flask with 4 glass beads of about 7-8 mm in diameter, add methanol to the mark, dissolve by ultrasonication, cool, and dilute to the mark with methanol. Accurately measure 5 ml, place it in a 50 ml volumetric flask, add mobile phase to dilute to the mark, and shake well.

[0112] The chromatographic conditions were as follows: octadecylsilane bonded silica gel was used as filler (Phenomenex Gemini C18, 4.6 mm × 150 mm, 5 μm or a chromatographic column of equivalent performance); 0.025 mol / L potassium dihydrogen phosphate solution (pH adjusted to 7.5 with 20% sodium hydroxide solution)-acetonitrile (60:40) was used as the mobile phase; the detection wavelength was 243 nm; the column temperature was 30°C; the injection volume was 20 μl; and the flow rate was 1.0 ml / min.

[0113] The system suitability requires that the number of theoretical plates calculated based on the tandospirone peak be no less than 5000.

[0114] Determination method: Accurately measure the reference solution and the test solution, inject them into the liquid chromatograph respectively, record the chromatogram to about 1.3 times the retention time of the main component peak, and calculate the peak area according to the external standard method.

[0115] This method was used to test three batches of sustained-release preparations, and the results are shown in Table 4. Typical spectra are shown in Figure 1-2 As shown, Figure 1 A typical graph of a reference solution is shown in Figure 2. Figure 2 It is a typical diagram of the test solution. Analysis shows that the content determination method of the present application has high accuracy and high stability.

[0116] Table 4 Content determination of different batches of sustained-release preparations

[0117] batch number Measurement results 220201 101.0％ 220202 100.0％ 220203 100.5％

[0118] Example 5 Methodology Verification

[0119] The verification results of the method of the present invention are as follows:

[0120]

[0121]

[0122] The above methodological validation results show that the method system of the present invention has good applicability, strong specificity, good linearity and range, high accuracy, strong repeatability, good intermediate precision, strong solution stability and high durability.

[0123] The above is an explanation of the embodiments of the present invention. However, the present invention is not limited to the above embodiments. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A method for determining the content of a tandospirone sustained-release preparation, the method comprising the following steps: 1) Preparation of test solution: Take the tandospirone sustained-release preparation, add an appropriate amount of solvent to disintegrate the sustained-release preparation, make up to volume, and centrifuge to obtain the supernatant; 2) Content determination: Determine the content of tandospirone in the supernatant.

2. The content determination method according to claim 1, characterized in that: In step 1), the test solution is prepared by taking the tandospirone sustained-release preparation, adding an appropriate amount of solvent to disintegrate the sustained-release preparation without grinding, fixing the volume, and centrifuging to obtain a supernatant; Preferably, in step 1), the tandospirone sustained-release preparation is taken without grinding, weighed and placed in a container, an appropriate amount of solvent is added to disintegrate the sustained-release preparation, the solvent is continued to be added to the fixed volume, shaken well, and centrifuged to obtain a supernatant; Preferably, the solvent used in step 1) is methanol; Preferably, in step 1), grinding beads, such as glass beads, steel beads, ceramic beads, zirconia beads, etc., are pre-added in the container.

3. The content determination method according to claim 1 or 2, characterized in that: The tandospirone sustained-release preparation comprises tandospirone or a pharmaceutically acceptable salt thereof; Preferably, the tandospirone sustained-release preparation further comprises a hydrophilic gel material.

4. The content determination method according to claim 3, characterized in that: The hydrophilic gel material is selected from natural gums (such as sodium alginate, agar, tragacanth gum), cellulose derivatives, and polyethylene oxide; Preferably, the hydrophilic gel material is selected from at least one of methylcellulose (MC), hydroxymethylcellulose, sodium hydroxymethylcellulose (CMC-Na), hydroxyethylcellulose (HEC), hydroxypropylcellulose, hydroxypropylmethylcellulose (HPMC), carboxymethylcellulose, carboxyethylcellulose, microcrystalline cellulose, polyvidone (PVP), sodium alginate, carbomer, Kollidon SR, and polyethylene oxide; Preferably, HPMC is selected from at least one of HPMC A4M, HPMC E4M, HPMC E10M, HPMC K4M, HPMC K15M, HPMC K50M and HPMC K100M; Preferably, the polyethylene oxide is selected from one or more of polyethylene oxide WSR and polyethylene oxide N-80; Preferably, the polyethylene oxide is selected from one or more of polyethylene oxide WSR 303, polyethylene oxide WSR 1105, polyethylene oxide WSR301, polyethylene oxide WSR 205, and polyethylene oxide N-80; Preferably, the pharmaceutically acceptable salt is hydrochloride, sulfate, tartrate, oxalate, maleate, fumarate, citrate, methanesulfonate, p-toluenesulfonate, nitrate; preferably hydrochloride or citrate; more preferably citrate; Preferably, the tandospirone sustained-release preparations include tandospirone sustained-release tablets, tandospirone sustained-release pills, and tandospirone sustained-release capsules.

5. The method for determining the content of a substance according to any one of claims 1 to 4, characterized in that: Step 1) In the test solution, the concentration of tandospirone citrate is 0.05 mg / mL-5.0 mg / mL, preferably 0.1 mg / mL-2.0 mg / mL, more preferably 0.2 mg / mL-1.0 mg / mL, for example 0.6 mg / mL; And / or, in step 1), in the test solution, the concentration of the hydrophilic gel material is 0.1 mg / mL-10.0 mg / mL, preferably 0.5 mg / mL-5.0 mg / mL, more preferably 1.0 mg / mL-3.0 mg / mL, for example 2.2 mg / mL; And / or, in step 1), 5 tandospirone sustained-release tablets are taken, and the capacity of the container is 250 mL; And / or, in step 1), the mass ratio of the amount of grinding beads to tandospirone citrate is 1-20 beads: 50-200 mg, for example, 10 beads: 150 mg; and / or, in step 1), the mass ratio of the amount of grinding beads to the hydrophilic gel material is 1-20 beads: 200-1000 mg, for example, 10 beads: 550 mg; And / or, in step 1), the diameter of the grinding beads is 3-8 mm, preferably 6-8 mm; Preferably, step 1) specifically The method comprises the following steps: taking 5 tandospirone sustained-release tablets, accurately weighing them, placing them in a 250mL volumetric bottle pre-added with grinding beads, adding an appropriate amount of solvent to disintegrate the sustained-release preparation, continuing to add solvent to dilute to the scale of the volumetric bottle, shaking well, centrifuging, and obtaining a test solution.

6. The method for determining the content of a substance according to any one of claims 1 to 5, characterized in that: Step 1) further comprises a dilution step of the test solution: Take a certain amount of the test solution in step 1) into a volumetric flask, add an appropriate amount of solvent to further dissolve, then dilute to the scale of the volumetric flask with the mobile phase, shake well, filter, and obtain the diluted test solution; Preferably, the solvent used for dissolution is methanol; Preferably, the volume ratio of the test solution to the solvent volume is 1:1; Preferably, in the diluted test solution, the concentration of tandospirone citrate is 0.005 mg / mL-1.0 mg / mL, preferably 0.01 mg / mL-0.10 mg / mL, and more preferably 0.03 mg / mL; Preferably, in the diluted test solution, the concentration of the hydrophilic gel material is 0.01 mg / mL-2.0 mg / mL, preferably 0.05 mg / mL-0.5 mg / mL, and more preferably 0.11 mg / mL; Preferably, in the dilution step of the test solution, the mobile phase used for dilution includes phase A and phase B; phase A is 0.005 mol / L-0.2 mol / L (e.g., 0.025 mol / L) potassium dihydrogen phosphate aqueous solution, and phase B is acetonitrile; preferably, phase A: phase B = 60:40; preferably, phase A is further adjusted to a pH value of 7.5 with 20% sodium hydroxide solution; Preferably, the dilution step of the test solution is specifically as follows: Take 5 mL of the test solution in step 1) into a 100 mL volumetric flask, add 5 mL of solvent to further dissolve, then dilute to the scale of the volumetric flask with mobile phase, shake well, and filter to obtain the diluted test solution.

7. The method for determining the content of a substance according to any one of claims 1 to 6, characterized in that: In step 2), the content is determined by high performance liquid chromatography; Preferably, in step 2), the content is calculated by peak area using an external standard method; Preferably, in step 2), the chromatogram is recorded to about 1.3 times the retention time of the main component peak; Preferably, the chromatographic conditions for content determination in step 2) are: Chromatographic column: octadecylsilane bonded silica gel is used as filler, such as C18; preferably, the size of the chromatographic column is 4.6 mm × 150 mm, 5 μm; The mobile phase conditions are: phase A is 0.005 mol / L-0.2 mol / L (e.g. 0.025 mol / L) potassium dihydrogen phosphate aqueous solution, phase B is acetonitrile; isocratic elution; The detection wavelength is 240nm-246nm, for example 243nm; The column temperature is 20°C-40°C, for example 30°C; Injection volume 5μl-50μl, for example 20μl; Flow rate: 0.8-1.2 ml / min; Preferably, phase A:phase B=60:40; Preferably, the pH value of phase A is further adjusted to 7.5 using 20% ​​sodium hydroxide solution.

8. The method for determining the content of a substance according to any one of claims 1 to 7, characterized in that: The content determination method also includes the following steps: 3) Preparation of reference substance solution: accurately weigh the reference substance, place it in a container, add a solvent to dissolve the reference substance, and make up the volume; the reference substance is tandospirone or a pharmaceutically acceptable salt thereof; Preferably, the solvent used in step 3) is methanol; Preferably, in step 3), grinding beads, such as glass beads, steel beads, ceramic beads, zirconium oxide beads, etc., are pre-added in the container; Preferably, in step 3), the concentration of the reference solution is 0.2 mg / mL-0.4 mg / mL, for example 0.3 mg / mL; Preferably, in step 3), the mass ratio of the amount of grinding beads to tandospirone citrate is 1-10 beads: 10-100 mg, for example, 4 beads: 30 mg; Preferably, in step 3), the diameter of the grinding beads is 3-8 mm, preferably 6-8 mm; Preferably, step 3) specifically includes the following steps: accurately weigh 30 mg of the reference substance, place it in a 100 mL volumetric flask pre-added with grinding beads, add a solvent to dissolve the reference substance, and then dilute it with a solvent to the volume of the volumetric flask; the reference substance is tandospirone or a pharmaceutically acceptable salt thereof.

9. The content determination method according to claim 8, characterized in that: Step 3) further comprises a dilution step of the reference solution: Take a certain amount of the reference substance solution in step 3) into a volumetric flask, dilute it to the mark on the volumetric flask with the mobile phase, shake well, and filter to obtain the diluted reference substance solution; Preferably, in the dilution step of the reference solution, the mobile phase used for dilution includes phase A and phase B; phase A is 0.005 mol / L-0.2 mol / L (e.g., 0.025 mol / L) potassium dihydrogen phosphate aqueous solution, and phase B is acetonitrile; preferably, phase A: phase B = 60:40; preferably, phase A is further adjusted to a pH value of 7.5 using a 20% sodium hydroxide solution; Preferably, the concentration of the diluted reference solution is 0.005 mg / mL-1.0 mg / mL, preferably 0.01 mg / mL-0.10 mg / mL, more preferably 0.02 mg / mL-0.04 mg / mL, for example 0.03 mg / mL.

10. The content determination method according to any one of claims 1 to 9, characterized in that: The tandospirone sustained-release preparation may also optionally contain a filler, a bleaching agent, a lubricant, and a binder; Preferably, in the tandospirone sustained-release preparation, the content of the active pharmaceutical ingredient is 1-15% (preferably 2.5-10%), and the content of the hydrophilic gel material is 5-75% (preferably 15-65%, and further preferably 15-61.7%); Preferably, the tandospirone sustained-release preparation comprises the following components in percentage by weight: Active pharmaceutical ingredient 1-15% Hydrophilic gel material 5-75% Adhesive 0-20% Filler 15-80% Bleach aid 1-20% Lubricant 0.5-5%; Preferably, the filler is selected from one or a combination of lactose, sucrose, microcrystalline cellulose, pregelatinized starch, mannitol, sorbitol, xylitol, glucose, calcium sulfate, calcium hydrogen phosphate, calcium phosphate, calcium chloride, aluminum chloride, sodium chloride, calcium oxide, zinc oxide, and magnesium oxide; preferably microcrystalline cellulose; Preferably, the bleaching agent is selected from one or a combination of sodium carbonate, sodium bicarbonate, potassium bicarbonate, magnesium carbonate, and calcium carbonate; preferably, the bleaching agent is selected from sodium carbonate and / or sodium bicarbonate; Preferably, the lubricant is selected from one or a combination of talc, micro-powdered silica gel, magnesium stearate, calcium stearate, zinc stearate, sodium stearyl fumarate, magnesium lauryl sulfate, sodium lauryl sulfate, and hydrogenated vegetable oil; preferably magnesium stearate; Preferably, the binder is selected from one or a combination of polyvinyl pyrrolidone, gelatin, xanthan gum, dextrin, polyvinyl alcohol, carboxymethyl cellulose; preferably, the binder is selected from polyvinyl pyrrolidone and / or polyvinyl alcohol.

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