Method for detecting dissolution rate of rimantadine hydrochloride preparation
Through a method including preparation of test solution and reference solution and gas chromatography detection, the dissolution of adamantine hydrochloride preparation was detected, and the problem of lack of dissolution detection methods in the prior art was solved, and rapid and accurate The low-cost inspection effect ensures the timeliness and accuracy of product quality control.
Patent Information
- Application Number
- CN202411713652.X
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2024-11-27
- Publication Date
- 2025-02-18
AI Technical Summary
The prior art lacks a method to detect the dissolution of adamantine hydrochloride preparations, which leads to the inability to accurately calculate its release rate in the human body, affecting product quality control.
A method including preparation of test solution and reference solution and gas chromatography detection is adopted. By mixing adamantine hydrochloride preparation with a dissolution medium, adding alkali and internal standard solution, leaving it stand and layering, gas chromatography detection is carried out. The dissolution of the adamantine hydrochloride preparation was calculated.
A fast, accurate and low-cost detection method is realized, and the sample pre-processing can be completed within 30 minutes, meeting the rapid detection needs in the production process, and is not affected by physiological factors and instrument temperature differences in the body, ensuring the detection results. Timeliness and accuracy.
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Figure CN119470716A_ABST
Abstract
Description
Technical Field
[0001] The invention relates to the field of chemical drug analysis, in particular to a method for detecting the dissolution of a rimantadine hydrochloride preparation. Background Art
[0002] Rimantadine hydrochloride preparations are mainly active against influenza A virus, and act in the early stage of the viral replication cycle by inhibiting the uncoating of viral particles in host cells. They are suitable for preventing influenza A virus infection in adults and children.
[0003] Zhao Yu, Yu Xiaohong. Determination of the content of rimantadine hydrochloride tablets by capillary gas chromatography. Heilongjiang Science and Technology Information. (2012.34) discloses a method for determining the content of rimantadine hydrochloride tablets by gas chromatography, but there is still a lack of detection methods for the dissolution of rimantadine hydrochloride preparations, so it is impossible to accurately calculate the release rate of rimantadine hydrochloride preparations in the human body. Only by developing a detection method for the dissolution of rimantadine hydrochloride preparations can the quality of rimantadine hydrochloride preparations be better controlled. Summary of the invention
[0004] The object of the present invention is to provide a method for detecting the dissolution of a rimantadine hydrochloride preparation which is simple, rapid and highly accurate.
[0005] To achieve the purpose of the present invention, the technical solution is as follows:
[0006] A method for detecting the dissolution of a rimantadine hydrochloride preparation, the method comprising: preparing a test solution: mixing the rimantadine hydrochloride preparation with a dissolution medium, dissolving, filtering the obtained dissolution solution, adding a base and an internal standard solution, and standing to separate layers;
[0007] Preparation of reference solution: Mix the rimantadine hydrochloride reference with the dissolution medium, dissolve, filter the obtained liquid, add alkali and internal standard solution, and let stand to separate;
[0008] The test solution and the reference solution are subjected to gas chromatography detection to calculate the solubility of the rimantadine hydrochloride preparation;
[0009] The internal standard solution is prepared by dissolving adamantane in n-hexane; the dissolution medium is selected from any one of hydrochloric acid solution, acetate buffer, and phosphate buffer; the solubility of the adamantane hydrochloride preparation refers to the calculation of peak area by the internal standard method.
[0010] Furthermore, the concentration of the internal standard solution is 0.35 mg / ml. When the reference solution is prepared, the concentration of the rimantadine hydrochloride reference substance in the dissolution medium is 0.2 mg / ml; and the concentration of the rimantadine hydrochloride preparation dissolution solution is 0.2 mg / ml.
[0011] Furthermore, the alkali is selected from sodium hydroxide solution. Preferably, the concentration of the sodium hydroxide solution is 1 mol / L.
[0012] Furthermore, the dissolution medium is selected from 0.1 mol / L hydrochloric acid solution, pH 4.5 acetate buffer, and pH 6.8 phosphate buffer.
[0013] Furthermore, when preparing the test solution, 500 ml of the dissolution medium is used, and the dissolution is carried out by a paddle method at 50 rpm for 15-45 minutes. Furthermore, 10 ml of the obtained dissolution solution is taken, filtered, 2 ml of the filtrate is taken, and 5 ml of the alkaline solution is added.
[0014] Furthermore, when preparing the test solution and the reference solution, 1 ml of the internal standard solution was added, the solution was allowed to stand for stratification, and the n-hexane layer was taken.
[0015] Further, when the reference solution is prepared, the concentration of the rimantadine hydrochloride reference substance in the dissolution medium is 0.2 mg / ml. Then, 2 ml of the liquid is taken, 5 ml of the alkaline solution is added, and the internal standard solution is added, and the preparation is performed according to the above method.
[0016] Furthermore, the gas chromatography uses a chromatographic column with 5% phenyl-95% methyl polysiloxane as the stationary liquid.
[0017] Furthermore, the column temperature was 150°C, the injection port was 210°C-230°C, the detector was 240°C-260°C, and the injection volume was 2 μL.
[0018] The above-mentioned rimantadine hydrochloride preparations include tablets, granules, capsules, etc., and rimantadine hydrochloride granules are preferred.
[0019] Compared with the prior art, the present invention has the following significant advantages: the sample pretreatment of the detection method of the present invention only requires 30 minutes, which can meet the requirements of rapid detection in the production process to ensure the timeliness of the test data; at the same time, the cost is low, it is not interfered by physiological factors in the body, it is not affected by small temperature differences of the instrument, it can more sensitively reflect the characteristics of the preparation, and the method is simple, fast and inexpensive; it has high accuracy, and can meet the requirements of the determination of the dissolution curve of the rimantadine hydrochloride preparation when changing different instruments, different experimenters, different experimental times, different chromatographic conditions and different batches of samples. BRIEF DESCRIPTION OF THE DRAWINGS
[0020] Figure 1 It is a gas chromatogram of a blank sample and a blank excipient sample in which the dissolution medium is 0.1 mol / L hydrochloric acid solution in Example 2 of the present invention. Figure 1 A is the gas chromatogram of the blank sample. Figure 1 B is the gas chromatogram of the blank excipient sample.
[0021] Figure 2It is the gas chromatogram of the reference substance and the test substance in Example 2 of the present invention whose dissolution medium is 0.1 mol / L hydrochloric acid solution. Figure 2 A is the gas chromatogram of the reference substance. Figure 2 B is the gas chromatogram of the test product.
[0022] Figure 3 It is a gas chromatogram of the blank acetate buffer solution and the blank auxiliary material sample of the dissolution medium in Example 2 of the present invention. Figure 3 A is the gas chromatogram of the blank sample. Figure 3 B is the gas chromatogram of the blank excipient sample.
[0023] Figure 4 It is the gas chromatogram of the reference substance and the test substance in Example 2 of the present invention whose dissolution medium is acetate buffer. Figure 4 A is the gas chromatogram of the reference substance. Figure 4 B is the gas chromatogram of the test product.
[0024] Figure 5 It is a gas chromatogram of a blank sample and a blank excipient sample in which the dissolution medium is a phosphate buffer in Example 2 of the present invention. Figure 5 A is the gas chromatogram of the blank sample. Figure 5 B is the gas chromatogram of the blank excipient sample.
[0025] Figure 6 It is a gas chromatogram of a reference substance and a test substance in which the dissolution medium is a phosphate buffer solution in Example 2 of the present invention. Figure 6 A is the gas chromatogram of the reference substance. Figure 6 B is the gas chromatogram of the test product. DETAILED DESCRIPTION
[0026] The present invention is further illustrated by the following examples, but is not limited thereto.
[0027] Example 1 Dissolution time selection
[0028] The dissolution detection method of rimantadine hydrochloride granules comprises the following steps:
[0029] 1. Take a sample of rimantadine hydrochloride granules (100 mg) produced by the Zhongshan Branch of Zhuhai United Pharmaceutical Co., Ltd., and use the dissolution and release determination method of the "China Drug Inspection Standard Operation Specification" (2019 Edition) as the dissolution medium, with a paddle speed of 50 revolutions per minute, and operate according to the law. After 5, 10, 15, 20, 25, 30, and 45 minutes respectively (see Table 1 for details), take 10 ml of the solution, treat the dissolution solution as follows and perform the determination. Among them, the medium temperature is 37±0.5℃.
[0030] 2. Preparation of the test solution of rimantadine hydrochloride granules: Take 10 ml of the dissolution obtained in step 1, filter, accurately measure 2 ml of the filtrate, add 5 ml of 1 mol / L sodium hydroxide solution, shake, add 1 ml of internal standard solution for extraction, let stand to separate the layers, and take the n-hexane layer.
[0031] Preparation of reference solution: Take 10 mg of rimantadine hydrochloride reference substance, accurately weigh it, add an appropriate amount of methanol to dissolve it and quantitatively dilute it with 0.1 mol / L hydrochloric acid solution as the dissolution medium to make a solution of about 0.2 mg per 1 ml. Accurately measure 2 ml, add 5 ml of 1 mol / L sodium hydroxide solution, shake, add 1 ml of internal standard solution to extract, let stand and separate, and take the n-hexane layer.
[0032] Preparation of internal standard solution: Take an appropriate amount of adamantane, dissolve it in n-hexane and dilute it to make a solution containing 0.35 mg per 1 ml.
[0033] 3. Gas chromatography determination:
[0034] Instruments and equipment: Gas chromatograph, Equipment model: Agilent 6890N, Agilent 7890B, Manufacturer: Agilent Technologies Co., Ltd.
[0035] Chromatographic column: 5% phenyl-95% methyl polysiloxane as stationary liquid
[0036] Chromatographic conditions: Program temperature: column temperature 150°C, injection port 220°C, detector 250°C, injection volume 2 μL.
[0037] Determination method: Accurately pipette the reference solution and the test solution in step 2, inject them into the gas chromatograph, and determine. Calculate the dissolution rate by the internal standard method and peak area, see Table 1.
[0038] According to the above method, the difference is that the dissolution medium in step 1 is replaced with pH 4.5 acetate buffer and pH 6.8 phosphate buffer. The dissolution rate is calculated by gas chromatography using the internal standard method and peak area, as shown in Table 1.
[0039] Table 1
[0040]
[0041] As can be seen from Table 1, the dissolution medium of 0.1 mol / L hydrochloric acid solution / PH4.5 acetate buffer / PH6.8 phosphate buffer has a good solubility when the dissolution time is 15-45 minutes.
[0042] Example 2 Specificity Test
[0043] Blank solvent preparation: accurately measure 2 ml of 0.1 mol / L hydrochloric acid solution as the dissolution medium, add 5 ml of 1 mol / L sodium hydroxide solution, shake, add 1 ml of internal standard solution for extraction, let stand to separate the layers, and take the n-hexane layer.
[0044] Preparation of blank auxiliary material solution: weigh 18.5292g sucrose, 0.3137g stevioside, 0.0508g orange powder essence, mix well, weigh 1.885g mixed blank auxiliary material, put in a 500ml beaker, add 0.1mol / L hydrochloric acid solution as dissolution medium and shake to dissolve. Take an appropriate amount of solution and filter, accurately measure 2ml of the filtrate, add 5ml of 1mol / L sodium hydroxide solution, shake, add 1ml of internal standard solution to extract, let stand and separate, and take the n-hexane layer.
[0045] Preparation of the test sample: Use the sample batch number S240204 rimantadine hydrochloride granules produced by Jinling Pharmaceutical. According to the preparation method of the rimantadine hydrochloride granules test sample solution in Example 1, take an appropriate amount of the sample of the dissolution (the concentration of the dissolution is 0.2 mg / ml) after 15 minutes, take 10 ml of the dissolution, filter, accurately measure 2 ml of the filtrate, add 5 ml of 1 mol / L sodium hydroxide solution, shake, add 1 ml of internal standard solution to extract, let stand and separate, and take the n-hexane layer. The dissolution medium used is 0.1 mol / L hydrochloric acid solution.
[0046] Preparation of reference substance: Take the rimantadine hydrochloride reference substance, accurately weigh it, add an appropriate amount of methanol to dissolve it and quantitatively dilute it with a dissolution medium to make a solution of about 0.2 mg per 1 ml. Accurately measure 2 ml, add 5 ml of 1 mol / L sodium hydroxide solution, shake, add 1 ml of internal standard solution to extract, let it stand and separate, and take the n-hexane layer.
[0047] The internal standard solution in this embodiment is configured the same as in Example 1.
[0048] Chromatographic conditions: Program temperature: column temperature 150℃; injection port 220℃. Detector 250℃; injection volume 2 μL. Chromatographic column: 5% phenyl-95% methyl polysiloxane as stationary liquid.
[0049] Under the above chromatographic conditions, the blank solvent, blank excipient, reference solution, and test solution were tested by gas chromatography. The results are shown in Table 2 and Figure 1 , the blank solvent has no interference with the blank excipients and meets the specificity standards.
[0050] Table 2
[0051]
[0052] According to the above method, the blank solvent, blank excipient solution, and dissolution medium in the test solution were replaced with pH 4.5 acetate buffer and gas chromatography was performed. The results are shown in Table 3 and Figure 2 , the blank solvent has no interference with the blank excipients and meets the specificity standards.
[0053] Table 3
[0054]
[0055] According to the above method, the dissolution medium in the blank solvent, blank excipient solution, and test solution was replaced with pH 6.8 phosphate buffer and gas chromatography was performed. The results are shown in Table 4 and Figure 3 , the blank solvent has no interference with the blank excipients and meets the specificity standards.
[0056] Table 4
[0057]
[0058] Example 3 Stability Test
[0059] Test sample stock solution: Use the rimantadine hydrochloride granules produced by Jinling Pharmaceutical, and follow the method for preparing the test sample solution of rimantadine hydrochloride granules in Example 1. Take 50 ml of the sample at 15 minutes, filter it, and use it as the test sample stock solution with a concentration of 0.2 mg / ml.
[0060] Test solution: Take an appropriate amount of the test stock solution, filter, accurately measure 2 ml of the filtrate, add 5 ml of 1 mol / L sodium hydroxide solution, shake, add 1 ml of the internal standard solution to extract, let stand to separate, and take the n-hexane layer. The internal standard solution is prepared in the same way as in Example 1.
[0061] The test solution was tested at 2h, 2h, 4h, 6h, 12h, 18h, 24h, and 26h according to the detection method of the chromatographic conditions in Example 2, and the stability of the solution was investigated using the ratio of the main peak area to the internal standard as an indicator. The results are shown in Table 5:
[0062] Table 5
[0063]
[0064] The above method was followed, except that the dissolution medium in the test sample stock solution was replaced with pH 4.5 acetate buffer and pH 6.8 phosphate buffer. The results are shown in Tables 6 and 7.
[0065] Table 6
[0066]
[0067] Table 7
[0068]
[0069] It can be seen from the data in the above table that the test solution can be stable within 26 hours using the dissolution media of 0.1 mol / L hydrochloric acid solution, pH 4.5 acetate buffer, and pH 6.8 phosphate buffer.
[0070] Example 4 Linearity Test
[0071] Preparation of reference stock solution: Accurately weigh an appropriate amount of rimantadine hydrochloride reference substance, add an appropriate amount of methanol (about 1-2 ml) to dissolve it, and quantitatively dilute it with different dissolution media (0.1 mol / L hydrochloric acid solution, pH 4.5 acetate buffer, pH 6.8 phosphate buffer) to make a solution containing about 400 micrograms of rimantadine hydrochloride per 1 ml, and filter to obtain.
[0072] Linear solution preparation: Accurately measure 0.2ml, 0.5ml, 1.0ml, 1.5ml, and 2.0ml of the reference stock solution, add 5ml of 1mol / L sodium hydroxide solution to each, shake, add 1ml of internal standard solution to extract, let stand to separate layers, and take the n-hexane layer. Prepare five reference solutions of different concentrations.
[0073] Take 2 μl of each of the above reference solution and inject it into gas chromatography. The chromatographic conditions are the same as those in Example 2. Linear regression analysis is performed on the peak area using the injection volume, wherein the concentration of rimantadine hydrochloride is used as the abscissa and the main peak area and the internal standard peak area are used as the ordinate to obtain a linear equation and correlation coefficient R. The results are shown in Tables 8 to 10 below:
[0074] Table 8
[0075]
[0076] Table 9
[0077]
[0078] Table 10
[0079]
[0080] From Tables 8 to 10, it can be seen that the R values in the tables meet the linear standard, indicating that the detection method has a good linear relationship using the dissolution medium 0.1 mol / L hydrochloric acid solution, pH 4.5 acetate buffer, and pH 6.8 phosphate buffer.
[0081] Example 5 Accuracy Test
[0082] Test solution: weigh about 100 mg of six portions of rimantadine hydrochloride reference substance, add about 1.885 g of mixed blank excipients (see the mixed blank excipients in Example 2 for the ratio and composition), add 500 ml of dissolution medium (0.1 mol / L hydrochloric acid solution / PH4.5 acetate buffer / PH6.8 phosphate buffer) and dissolve by ultrasonic, filter, accurately measure 2 ml of the filtrate, add 5 ml of 1 mol / L sodium hydroxide solution, shake, add 1 ml of internal standard solution to extract, let stand to separate, and take the n-hexane layer. Preparation of internal standard solution: take an appropriate amount of adamantane, dissolve and dilute with n-hexane to make a solution containing about 0.35 mg per 1 ml.
[0083] The preparation of the reference solution and the gas chromatography conditions were the same as those in Example 2. Six portions of the test solution were prepared in parallel, each portion was measured twice in parallel, and the results of the 12 measurements were used for evaluation, as shown in Tables 11 to 13.
[0084] Table 11
[0085]
[0086] Table 12
[0087]
[0088] Table 13
[0089]
[0090] Example 6 Intermediate Precision Experiment
[0091] Take a sample of rimantadine hydrochloride granules, and according to the dissolution and release determination method of the "Chinese Drug Inspection Standard Operation Specification" (2019 Edition), use 500 ml of 0.1 mol / L hydrochloric acid solution, PH4.5 acetate buffer, and PH6.8 phosphate buffer as the dissolution medium (dissolution concentration is 0.2 mg / ml), and operate according to the paddle method at a speed of 50 revolutions per minute. After 15 minutes, take 10 ml of the solution. Among them, the medium temperature is 37±0.5℃.
[0092] Preparation of the test solution of rimantadine hydrochloride granules: Take 10 ml of the dissolution obtained in step 1, filter, accurately measure 2 ml of the filtrate, add 5 ml of 1 mol / L sodium hydroxide solution, shake, extract with 1 ml of internal standard solution, let stand to separate, and take the n-hexane layer. Preparation of the reference solution: Take 10 mg of rimantadine hydrochloride reference, accurately weigh, add an appropriate amount of methanol to dissolve, and quantitatively dilute with 0.1 mol / L hydrochloric acid solution as the dissolution medium to make a solution of about 0.2 mg per 1 ml, accurately measure 2 ml, add 5 ml of 1 mol / L sodium hydroxide solution, shake, extract with 1 ml of internal standard solution, let stand to separate, and take the n-hexane layer.
[0093] Preparation of internal standard solution: Take an appropriate amount of adamantane, dissolve it in n-hexane and dilute it to make a solution containing about 0.35 mg per 1 ml.
[0094] Gas chromatography determination: Instrument: Gas chromatograph, Equipment model: Agilent 6890N, Agilent 7890B, Manufacturer: Agilent Technologies Co., Ltd.
[0095] Chromatographic column: 5% phenyl-95% methyl polysiloxane as stationary liquid
[0096] Chromatographic conditions: Program temperature: column temperature 150°C, injection port 220°C, detector 250°C, injection volume 2 μL.
[0097] In the same laboratory, at different times, different experimenters used different gas chromatographs (same model) to prepare six parallel portions of 100% test solution, injected the reference substance and test solution into the gas chromatograph, and measured the experimental results of the 12 samples, as shown in Tables 14 to 16 below:
[0098] Table 14
[0099]
[0100] Table 15
[0101]
[0102] Table 16
[0103]
[0104] Example 7 Durability Test
[0105] Take a sample of rimantadine hydrochloride granules, and according to the dissolution and release determination method of the "Chinese Drug Inspection Standard Operation Specification" (2019 Edition), use 500 ml of 0.1 mol / L hydrochloric acid solution, PH4.5 acetate buffer, and PH6.8 phosphate buffer as the dissolution medium (concentration of 0.2 mg / ml), and operate according to the paddle method at a speed of 50 revolutions per minute. After 15 minutes, take 10 ml of the solution. Among them, the medium temperature is 37±0.5℃.
[0106] Preparation of the test solution of rimantadine hydrochloride granules: Take 10 ml of the obtained dissolution solution, filter, accurately measure 2 ml of the filtrate, add 5 ml of 1 mol / L sodium hydroxide solution, shake, add 1 ml of the internal standard solution to extract, let stand to separate, and take the n-hexane layer. Preparation of the reference solution: Take the rimantadine hydrochloride reference, accurately weigh, add an appropriate amount of methanol to dissolve, and quantitatively dilute with 0.1 mol / L hydrochloric acid solution as the dissolution medium to make a solution of about 0.2 mg per 1 ml, accurately measure 2 ml, add 5 ml of 1 mol / L sodium hydroxide solution, shake, add 1 ml of the internal standard solution to extract, let stand to separate, and take the n-hexane layer.
[0107] Preparation of internal standard solution: Take an appropriate amount of adamantane, dissolve it in n-hexane and dilute it to make a solution containing about 0.35 mg per 1 ml.
[0108] Gas chromatography determination: Chromatographic column: 5% phenyl-95% methyl polysiloxane as the stationary liquid column
[0109] Inject the reference and test solutions into the gas chromatograph at a column temperature of 150°C and an injection volume of 2 μL. The injection port and detector temperature adjustments are shown in Tables 18 to 20.
[0110] Table 18
[0111]
[0112] Table 19
[0113]
[0114] Table 20
[0115]
[0116] Example 8 Different manufacturers and different batches
[0117] Take samples of rimantadine hydrochloride granules from different manufacturers and batches, and according to the dissolution and release determination method of the "Chinese Drug Inspection Standard Operation Specification" (2019 Edition), use 500 ml of 0.1 mol / L hydrochloric acid solution, PH4.5 acetate buffer, and PH6.8 phosphate buffer as the dissolution medium (concentration of 0.2 mg / ml), and operate according to the paddle method at a speed of 50 revolutions per minute. After 15 minutes, take 10 ml of the solution. Among them, the medium temperature is 37±0.5℃.
[0118] Preparation of the test solution of rimantadine hydrochloride granules: Take 10 ml of the obtained dissolution solution, filter, accurately measure 2 ml of the filtrate, add 5 ml of 1 mol / L sodium hydroxide solution, shake, add 1 ml of the internal standard solution to extract, let stand to separate, and take the n-hexane layer. Preparation of the reference solution: Take the rimantadine hydrochloride reference, accurately weigh, add an appropriate amount of methanol to dissolve, and quantitatively dilute with 0.1 mol / L hydrochloric acid solution as the dissolution medium to make a solution of about 0.2 mg per 1 ml, accurately measure 2 ml, add 5 ml of 1 mol / L sodium hydroxide solution, shake, add 1 ml of the internal standard solution to extract, let stand to separate, and take the n-hexane layer.
[0119] Preparation of internal standard solution: Take an appropriate amount of adamantane, dissolve it in n-hexane and dilute it to make a solution containing about 0.35 mg per 1 ml.
[0120] Gas chromatography determination: chromatographic column with 5% phenyl-95% methyl polysiloxane as stationary liquid
[0121] The reference and test solutions were injected into the gas chromatograph (chromatographic conditions: column temperature 150°C, injection port 220°C, detector 250°C) with an injection volume of 2 μL. The results are shown in Table 21.
[0122] Table 21
[0123]
Claims
1. A method for detecting the dissolution rate of a rimantadine hydrochloride preparation, characterized in that: The method comprises: preparing a test solution: mixing a rimantadine hydrochloride preparation with a dissolution medium, dissolving, filtering the obtained dissolution solution, adding a base and an internal standard solution, and standing to separate layers; Preparation of reference solution: Mix the rimantadine hydrochloride reference with the dissolution medium, dissolve, filter the obtained liquid, add alkali and internal standard solution, and let stand to separate; The obtained test solution and reference solution are subjected to gas chromatography detection to calculate the solubility of the memantine hydrochloride sustained-release preparation; The internal standard solution is prepared by dissolving adamantane in n-hexane; the dissolution medium is selected from any one of hydrochloric acid solution, acetate buffer and phosphate buffer; The solubility of the rimantadine hydrochloride preparation refers to the calculation of peak area using the internal standard method.
2. The method for detecting the dissolution rate of a rimantadine hydrochloride preparation according to claim 1, characterized in that: The concentration of the internal standard solution is 0.35 mg / ml; when the reference solution is prepared, the concentration of the rimantadine hydrochloride reference substance in the dissolution medium is 0.2 mg / ml; and the concentration of the rimantadine hydrochloride preparation dissolution solution is 0.2 mg / ml.
3. The method for detecting the dissolution rate of a rimantadine hydrochloride preparation according to claim 1, characterized in that: The base is selected from sodium hydroxide solution.
4. The method for detecting the dissolution rate of a rimantadine hydrochloride preparation according to claim 3, characterized in that: The sodium hydroxide solution is 1 mol / L.
5. The method for detecting the dissolution rate of a rimantadine hydrochloride preparation according to claim 1, characterized in that: The dissolution medium is selected from 0.1 mol / L hydrochloric acid solution, pH 4.5 acetate buffer, and pH 6.8 phosphate buffer.
6. The method for detecting the dissolution rate of a rimantadine hydrochloride preparation according to claim 1, characterized in that: When preparing the test solution, use 500 ml of dissolution medium and use the paddle method at 50 rpm for 15-45 minutes.
7. The method for detecting the dissolution rate of a rimantadine hydrochloride preparation according to claim 6, characterized in that: When preparing the test solution, take 10 ml of the obtained eluate, filter it, take 2 ml of the filtrate, and add 5 ml of the alkaline solution.
8. The method for detecting the dissolution rate of a rimantadine hydrochloride preparation according to claim 7, characterized in that: When preparing the test solution and the reference solution, add 1 ml of the internal standard solution, let it stand to separate the layers, and take the n-hexane layer.
9. The method for detecting the dissolution rate of a rimantadine hydrochloride preparation according to claim 1, characterized in that: The gas chromatography uses a chromatographic column with 5% phenyl-95% methylpolysiloxane as a stationary liquid.
10. The method for detecting the dissolution rate of a rimantadine hydrochloride preparation according to claim 9, characterized in that: The column temperature was 150°C, the injection port was 210°C-230°C, the detector was 240°C-260°C, and the injection volume was 2 μL.