Method for determining content of sucrose octasulfate potassium salt
By using the mixing of cation exchange SCX filler and C18 filler as a filler in the assay, combined with an electrospray detector and a specific mobile phase, the problem of difficulty in determining the potassium salt content of sucrose octasulfate in the prior art is solved, and high efficiency is achieved , accurate quantitative analysis ensures the quality of the drug and significantly improves reproducibility and peak shape.
Patent Information
- Application Number
- CN202310789363.7
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2023-06-30
- Publication Date
- 2024-12-31
AI Technical Summary
The existing assays cannot effectively quantify the potassium salt content of sucrose octasulfate, and the peak type is poor, the retention time drifts seriously, the chromatographic column is not durable, difficult to repeat and amplify, and effective detection cannot be achieved.
The cation exchange SCX filler and C18 filler are mixed at 1:3 to 5 as filler, and 50mM/L ammonium acetate and acetonitrile are used as mobile phases. The detector is an electrospray detector, which sets the spray temperature high and the half-maximum width of the acquisition frequency. It is 0.1 min, column temperature is 28-32 °C, flow rate is 0.7-0.9 ml/min, injection volume is 3-7 μl, running time is 8-12 min, and sucrose octasulfate potassium salt control solution is prepared by water as a diluent, and the recording is made Chromatogram, the content is calculated according to the external standard method of dry product.
It has achieved effective quantitative determination of potassium salt of sucrose octasulfate, strictly controlled the quality of the drug, greatly saved time using CAD detector, strong cation exchange and reverse particle mixing column have good reproducibility, better peak type and good repeatability, It has great positive progress and practical application value.
Smart Images
Figure CN119224188A_ABST
Abstract
Description
Technical Field
[0001] The invention belongs to the field of medicine, and particularly relates to a method for determining the content of sucrose octasulfate potassium salt. Background Art
[0002] The quality standard of sucrose octasulfate potassium salt as an auxiliary material is not included in the pharmacopoeias of various countries. Refer to the general chapter 0512 of the "Chinese Pharmacopoeia (2020 Edition)" for high-performance liquid chromatography; although the document "HPLC method for determining the content of sucrose octasulfate in sucralfate tablets" discloses a test method, it uses an amino column and a differential refractometer detector, with poor peak shape, severe retention time drift, chromatographic column intolerance, and difficulty in repeating and amplification, and still cannot achieve the above detection. Therefore, it is urgent to develop a method for determining the content of sucrose octasulfate potassium salt, which can effectively quantify the content of sucrose octasulfate potassium, so as to strictly control the quality of drugs. Summary of the invention
[0003] The purpose of the present invention is to provide a method for determining the content of sucrose potassium octasulfate, which is a must for controlling the content of sucrose potassium octasulfate and can effectively quantify the content of sucrose potassium octasulfate, thereby strictly controlling the quality of drugs.
[0004] The present invention provides the following technical solutions:
[0005] A method for determining the content of sucrose octasulfate potassium salt, the steps are as follows:
[0006] Use cation exchange SCX filler and C18 filler mixed in a ratio of 1:3-5 as filler;
[0007] Use 50mM / L ammonium acetate and acetonitrile as the mobile phase, ammonium acetate: acetonitrile = 90-100: 3-7, isocratic elution;
[0008] The detector was an electrospray detector, the spray temperature was set to High, the half-peak width of the acquisition frequency was 0.1 min; the column temperature was 28-32°C; the flow rate was 0.7-0.9 ml / min; the injection volume was 3-7 μl; the run time was 8-12 min;
[0009] Use water as the diluent, take an appropriate amount of sucrose octasulfate potassium salt reference substance to prepare a reference substance solution containing 2 mg of sucrose octasulfate potassium salt per 1 ml, take 5 μl of the reference substance solution and inject it into the liquid chromatograph to record the chromatogram.
[0010] Take 20 mg of this product, weigh it accurately, put it in a 10 ml volumetric bottle, dissolve it with diluent and dilute it to the scale, shake it well, and use it as the test solution; accurately measure 5 μl of the test solution and reference solution and inject them into the liquid chromatograph to record the chromatogram. Calculated by the dry product external standard method, the content of potassium sucrose octasulfate (SOS) in this product should be 90.0% to 110.0%, and the content of potassium salt (K) should be 90.0% to 110.0%.
[0011] Preferably, the cation exchange SCX filler and the C18 filler are mixed in a ratio of 1:4 as the filler.
[0012] Preferably, the chromatographic column model is CAPCELLPAKCRC18+SCX5μm, 250×4.6mml.D.
[0013] Preferably, the mobile phase is ammonium acetate: acetonitrile = 95:5
[0014] Preferably, the column temperature is 30°C; the flow rate is 0.8 ml / min; the injection volume is 5 μl; and the running time is 10 min.
[0015] Preferably, the theoretical plate numbers of the sucrose octasulfate peak and the potassium peak in the reference solution are greater than 2000.
[0016] Beneficial effects of the present invention:
[0017] The present invention solves the problem of determining the content of sucrose potassium octasulfate, is a must for controlling the content of sucrose potassium octasulfate, and can effectively quantify the content of sucrose potassium octasulfate, thereby strictly controlling the quality of the drug. The quality control of sucrose potassium octasulfate of the present invention uses a CAD detector for determination in the establishment of an analytical method, which can greatly save time, and uses a strong cation exchange and reverse particle mixed column CAPCELLPAKCR with good reproducibility, better peak shape, and good repeatability, and has a large positive improvement effect and practical application value. BRIEF DESCRIPTION OF THE DRAWINGS
[0018] The accompanying drawings are used to provide a further understanding of the present invention and constitute a part of the specification. Together with the embodiments of the present invention, they are used to explain the present invention and do not constitute a limitation of the present invention. In the accompanying drawings:
[0019] Figure 1 This is a typical chromatogram of the reference solution in implementation case 1;
[0020] Figure 2 This is a typical chromatogram of the test solution in implementation case 1;
[0021] Figure 3 This is a typical chromatogram of the reference solution in implementation case 2;
[0022] Figure 4This is a typical chromatogram of the test solution in implementation case 3;
[0023] Figure 5 This is a typical chromatogram of the reference solution in implementation case 3;
[0024] Figure 6 This is a typical chromatogram of the test solution in implementation case 3. DETAILED DESCRIPTION
[0025] Embodiment 1:
[0026] The method for determining the content of sucrose octasulfate potassium salt is as follows:
[0027] A cation exchange SCX filler and a C18 filler were mixed in a ratio of 1:3 as a filler, and the chromatographic column model was CAPCELLPAKCRC18+SCX5μm, 250×4.6mml.D.; 50mM / L ammonium acetate and acetonitrile were used as the mobile phase, ammonium acetate:acetonitrile=90:3, isocratic elution; the detector was an electrospray detector, the spray temperature was set to High, and the half-peak width of the acquisition frequency was 0.1min; the column temperature was 28°C; the flow rate was 0.7ml / min; the injection volume was 3μl; the running time was 8min; water was used as a diluent, and an appropriate amount of sucrose octasulfate potassium salt reference substance was taken to prepare a reference substance solution containing 2mg of sucrose octasulfate potassium salt per 1ml, and 5μ1 of the reference substance solution was injected into the liquid chromatograph, and the chromatogram was recorded, such as Figure 1 Take 20 mg of this product, weigh it accurately, put it in a 10 ml volumetric flask, dissolve it with a diluent and dilute it to the mark, shake it well, and use it as the test solution; accurately measure 5 μl of the test solution and the reference solution and inject them into the liquid chromatograph, record the chromatogram, such as Figure 2 Calculated by the external standard method of dry product, this product contains 98.8% sucrose octasulfate potassium (SOS) and 98.6% potassium salt (K).
[0028] Embodiment 2:
[0029] A cation exchange SCX filler and a C18 filler were mixed in a ratio of 1:4 as a filler, and the chromatographic column model was CAPCELLPAKCRC18+SCX5μm, 250×4.6mml.D.; 50mM / L ammonium acetate and acetonitrile were used as the mobile phase, ammonium acetate:acetonitrile = 95:5, isocratic elution; the detector was an electrospray detector, the spray temperature was set to High, and the half-peak width of the acquisition frequency was 0.1min; the column temperature was 30°C; the flow rate was 0.8ml / min; the injection volume was 5μl; the running time was 10min; water was used as a diluent, and an appropriate amount of sucrose octasulfate potassium salt reference substance was taken to prepare a reference substance solution containing 2mg of sucrose octasulfate potassium salt per 1ml, and 5μ1 of the reference substance solution was injected into the liquid chromatograph, and the chromatogram was recorded, as shown in FIG. Figure 3Take 20 mg of this product, weigh it accurately, put it in a 10 ml volumetric flask, dissolve it with a diluent and dilute it to the mark, shake it well, and use it as the test solution; accurately measure 5 μl of the test solution and the reference solution and inject them into the liquid chromatograph, record the chromatogram, such as Figure 4 Calculated by the external standard method of dry product, the content of sucrose octasulfate potassium (SOS) in this product is 98.3%, and the content of potassium salt (K) should be 98.1%.
[0030] Embodiment 3:
[0031] A cation exchange SCX filler and a C18 filler were mixed in a ratio of 1:5 as a filler, and the chromatographic column model was CAPCELLPAKCRC18+SCX5μm, 250×4.6mml.D.; 50mM / L ammonium acetate and acetonitrile were used as the mobile phase, ammonium acetate:acetonitrile=100:7, isocratic elution; the detector was an electrospray detector, the spray temperature was set to High, and the half-peak width of the acquisition frequency was 0.1min; the column temperature was 32°C; the flow rate was 0.9ml / min; the injection volume was 7μl; the running time was 12min; water was used as a diluent, and an appropriate amount of sucrose octasulfate potassium salt reference substance was taken to prepare a reference substance solution containing 2mg of sucrose octasulfate potassium salt per 1ml, and 5μ1 of the reference substance solution was injected into the liquid chromatograph, and the chromatogram was recorded, such as Figure 5 Take 20 mg of this product, weigh it accurately, put it in a 10 ml volumetric flask, dissolve it with a diluent and dilute it to the mark, shake it well, and use it as the test solution; accurately measure 5 μl of the test solution and the reference solution and inject them into the liquid chromatograph, record the chromatogram, such as Figure 6 Calculated by the external standard method of dry product, the content of sucrose octasulfate potassium (SOS) in this product is 98.7%, and the content of potassium salt (K) is 99.1%.
[0032] Research has found that the use of CAD detector in the establishment of analytical methods for quality control of sucrose octasulfate potassium salt can greatly save time, and the use of strong cation exchange and reverse particle mixed column CAPCELLPAKCR has good reproducibility, better peak shape, and good repeatability, which has great positive improvement effects and practical application value.
[0033] The above are only preferred embodiments of the present invention and are not intended to limit the present invention. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art can still modify the technical solutions described in the aforementioned embodiments or replace some of the technical features therein by equivalents. 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. The method for determining the content of sucrose octasulfate potassium salt is characterized in that: Here are the steps: Use cation exchange SCX filler and C18 filler mixed in a ratio of 1:3-5 as filler; Use 50mM / L ammonium acetate and acetonitrile as the mobile phase, ammonium acetate: acetonitrile = 90-100: 3-7, isocratic elution; The detector was an electrospray detector, the spray temperature was set to High, the half peak width of the acquisition frequency was 0.1 min; the column temperature was 28-32°C; the flow rate was 0.7-0.9 ml / min; the injection volume was 3-7 μl; the run time was 8-12 min; Use water as the diluent, take an appropriate amount of sucrose octasulfate potassium salt reference substance to prepare a reference substance solution containing 2 mg of sucrose octasulfate potassium salt per 1 ml, take 5 μl of the reference substance solution and inject it into the liquid chromatograph to record the chromatogram. Take 20 mg of this product, weigh accurately, put it in a 10 ml volumetric bottle, dissolve it with diluent and dilute it to the scale, shake well, and use it as the test solution; Accurately measure 5 μl of the test solution and the reference solution and inject them into the liquid chromatograph to record the chromatogram.
2. The method for determining the content of sucrose octasulfate potassium salt according to claim 1, wherein: The cation exchange SCX filler and C18 filler were mixed at a ratio of 1:4 as filler.
3. The method for determining the content of sucrose octasulfate potassium salt according to claim 1, wherein: The chromatographic column model is CAPCELLPAKCRC18+SCX5μm, 250×4.6mml.D.
4. The method for determining the content of sucrose octasulfate potassium salt according to claim 1, wherein: The mobile phase was ammonium acetate: acetonitrile = 95:
5.
5. The method for determining the content of sucrose octasulfate potassium salt according to claim 1, wherein: Column temperature 30°C; flow rate 0.8 ml / min; injection volume 5 μl; running time 10 min.
6. The method for determining the content of sucrose octasulfate potassium salt according to claim 1, characterized in that: The theoretical plate numbers of the sucrose octasulfate peak and potassium peak in the reference solution are greater than 2000.