Method for measuring content of atropine sulfate in compound aluminum hydroxide tablet

Abstract

The invention relates to the technical field of pharmaceutical analysis, in particular to a method for measuring the content of atropine sulfate in a compound aluminum hydroxide tablet, which comprises the following steps: mixing and dissolving monopotassium phosphate and sodium 1-pentane sulfonate in pure water to obtain a mixed solution; adjusting the pH value of the mixed solution to 2.5 + / -0.05 with phosphoric acid, and filtering to obtain a buffer solution; weighing atropine sulfate, and sequentially dissolving and diluting to obtain an atropine sulfate reference solution; weighing the compound aluminum hydroxide tablets, and adding a hydrochloric acid solution to obtain a sample solution; respectively detecting the atropine sulfate reference solution and the sample solution by adopting a high performance liquid chromatography; the determined chromatographic conditions and related analysis methods have the beneficial effects of high efficiency, accuracy, reliability and the like in the aspect of measuring the content of atropine sulfate in the compound aluminum hydroxide tablets.

Description

Technical Field

[0001] The invention relates to the technical field of drug analysis, and in particular to a method for determining the content of atropine sulfate in a compound aluminum hydroxide tablet. Background Art

[0002] In the field of drug analysis, it is very important to accurately determine the content of atropine sulfate in compound aluminum hydroxide tablets, which is of key significance for ensuring the quality of drugs and ensuring the safety and effectiveness of clinical drugs. High performance liquid chromatography (HPLC) technology, as a common and effective analytical method, has been widely used in the quantitative analysis of drug components. When the existing chromatographic analysis technology is applied to the determination of atropine sulfate content in compound aluminum hydroxide tablets, it is difficult to achieve effective separation, resulting in problems such as peak broadening and insufficient separation, causing the atropine sulfate peak to overlap or partially overlap with other impurity peaks, seriously affecting the accurate integration of peak area and the precise calculation of content, and thus failing to meet the requirements of modern drug quality control for high sensitivity and high resolution analysis; With the continuous improvement of drug quality standards and the continuous development of analytical technology, there is an urgent need for a more efficient, accurate and reliable method for determining the content of atropine sulfate to fill the defects of the existing technology, meet the strict requirements of compound aluminum hydroxide tablet quality control, and ensure that patients can use drugs with qualified quality and stable efficacy;

[0003] Therefore, the present invention aims to address the deficiencies in the above-mentioned prior art and propose a method for determining the content of atropine sulfate in compound aluminum hydroxide tablets, so as to improve the level of drug quality control and ensure the safety of public drug use. Summary of the invention

[0004] The purpose of the present invention is to provide a method for determining the content of atropine sulfate in a composite aluminum hydroxide tablet in view of the deficiencies in the prior art;

[0005] To achieve the above object, the technical solution adopted by the present invention is:

[0006] The present invention provides a method for determining the content of atropine sulfate in a composite aluminum hydroxide tablet, comprising the following steps:

[0007] Step 1, providing potassium dihydrogen phosphate, sodium 1-pentane sulfonate, phosphoric acid, acetonitrile, hydrochloric acid, atropine sulfate, and aluminum hydroxide;

[0008] Step 2, mixing and dissolving the potassium dihydrogen phosphate and the sodium 1-pentane sulfonate in pure water to obtain a mixed solution; adjusting the pH of the mixed solution to 2.5±0.05 with the phosphoric acid, and filtering to obtain a buffer solution;

[0009] Step 3,

[0010] The buffer solution and the acetonitrile are sequentially mixed in a ratio of 17:1-3, and ultrasonically degassed to obtain mobile phase A.

[0011] The buffer solution and the acetonitrile are sequentially mixed in a ratio of 1-3:7-9, and ultrasonically degassed to obtain mobile phase B;

[0012] Step 4, weighing the atropine sulfate, dissolving and diluting the atropine sulfate in sequence to obtain an atropine sulfate control solution;

[0013] Step 5, weighing the composite aluminum hydroxide tablets, adding hydrochloric acid solution, diluting to scale with the buffer solution, centrifuging, and filtering to obtain a sample solution;

[0014] Step six, respectively detecting the atropine sulfate control solution and the sample solution by high performance liquid chromatography.

[0015] Furthermore, in the step 1, the mass ratio of the potassium dihydrogen phosphate and the sodium 1-pentane sulfonate when mixed is 17-19:24-26;

[0016] Further, the concentration of the atropine sulfate control solution is

[0017] Furthermore, in the step 5,

[0018] 1 unit mass of the composite aluminum hydroxide tablet is added with 20-30 unit volumes of the hydrochloric acid solution;

[0019] Wherein, the concentration of the hydrochloric acid solution is 0.5mol / L-2mol / L.

[0020] Furthermore, in step six, the chromatographic column used in the high performance liquid chromatography is a reverse phase C18 column, and the column temperature of the chromatographic column during injection is 50°C-40°C.

[0021] Furthermore, in step six, the detector used in the high performance liquid chromatography is an ultraviolet detector, and the detection wavelength of the ultraviolet detector is 200nm-220nm.

[0022] Furthermore, in the step six, the flow rate of the mobile phase in the high performance liquid chromatography is 1 mL / min-3 mL / min, and the injection volume of the sample solution is 90 μL-110 μL.

[0023] Furthermore, the high performance liquid chromatography detection adopts gradient elution, and the gradient elution process is as follows:

[0024] At 11 min, the volume fraction of mobile phase A decreased from 92% to 79%, and the volume fraction of mobile phase B increased from 8% to 21%;

[0025] 11min-15min: the volume fraction of mobile phase A decreased from 97% to 46%, and the volume fraction of mobile phase B increased from 21% to 54%;

[0026] 15min-15.1min: the volume fraction of mobile phase A increased from 46% to 92%, and the volume fraction of mobile phase B decreased from 54% to 8%;

[0027] 15.1min-20min: the volume fraction of mobile phase A is maintained at 92%, and the volume fraction of mobile phase B is maintained at 8%;

[0028] The post-run time of mobile phase A and mobile phase B is 1 min-5 min.

[0029] The present invention adopts the above technical solution, and has the following technical effects compared with the prior art:

[0030] The chromatographic conditions and related analytical methods determined by the present invention have many beneficial effects such as high efficiency, accuracy and reliability in the determination of the content of atropine sulfate in the compound aluminum hydroxide tablets, and have important practical significance and application value for improving the quality control level of drugs. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 is the chromatogram of the blank solution of the present invention;

[0032] Figure 2 is the chromatogram of atropine sulfate reference substance of the present invention;

[0033] Figure 3 The chromatogram of the sample of the present invention. DETAILED DESCRIPTION

[0034] The specific embodiments of the present invention will be described in detail below.

[0035] Unless otherwise defined, technical or scientific terms used in the claims and the specification shall have the common meanings understood by persons having ordinary skills in the technical field to which the present invention belongs.

[0036] The words "include" or similar words used in the patent application specification and claims of the present invention mean that the items appearing before "include" include the items listed after "include" or their equivalents, and do not exclude other items.

[0037] The numerical values ​​mentioned in the present invention include all numerical values ​​that increase from low to high by one unit, assuming that there are at least two units between any lower value and the higher value. For example, if a component or a physical quantity is said to be from 1 to 100, 10 to 90 is more preferred, and 20 to 80 is the most preferred, it is intended to express that values ​​such as 5 to 95, 14 to 76, 23 to 67, 32 to 58, 41 to 49 are clearly listed in this specification; for values ​​less than 1, 0.0001, 0.001, 0.01 or 0.1 are considered to be more suitable as a unit. The above examples are for illustrative purposes only. In fact, all numerical combinations between the lowest value and the highest value listed are deemed to be clearly listed in this specification in a similar manner.

[0038] Example

[0039] This embodiment provides a method for determining the content of atropine sulfate in a composite aluminum hydroxide tablet, characterized in that it comprises the following steps:

[0040] Step 1, providing potassium dihydrogen phosphate, sodium 1-pentane sulfonate, phosphoric acid, acetonitrile, hydrochloric acid, atropine sulfate, and compound aluminum hydroxide tablets;

[0041] Step 2, weighing 1.8 g of the potassium dihydrogen phosphate and 2.5 g of the sodium 1-pentane sulfonate, dissolving them in water, and diluting them to 1000 ml to obtain a mixed solution; adjusting the pH of the mixed solution to 2.5±0.05 with the phosphoric acid, and filtering with a 0.45 μm filter membrane to obtain a buffer solution;

[0042] Step 3: Mobile phase preparation

[0043] Measure 1900 ml of buffer and 100 ml of acetonitrile, mix them in sequence, and degas by ultrasonication to obtain mobile phase A.

[0044] Measure 200 ml of buffer and 800 ml of acetonitrile, mix them in sequence, and degas by ultrasonication to obtain mobile phase B;

[0045] Step 4: Preparation of atropine sulfate control solution:

[0046] Weigh 10 mg of atropine sulfate reference substance, accurately weigh it, place it in a 50 ml volumetric flask, dissolve it in water and dilute it to the mark, shake it well, accurately measure 5.0 ml and place it in a 50 ml volumetric flask, dilute it to the mark with water, shake it well, accurately measure 2 ml and place it in a 50 ml volumetric flask, dilute it to the mark with buffer solution, shake it well, and make an atropine sulfate reference solution containing about 0.8 μg of atropine sulfate per 1 ml.

[0047] Step 5, sample solution preparation (prepare 2 in parallel):

[0048] Accurately weigh 1.0g of the fine powder under the content determination item of compound aluminum hydroxide tablets, place it in a 50ml volumetric flask, add 25ml of 1mol / L hydrochloric acid solution, shake for 2 to 5 minutes (to prevent the test solution from caking), ultrasonically extract for 15 minutes (shake once every 5 minutes), take it out, cool to room temperature, make up to the scale with buffer, shake well, centrifuge at 4000 rpm for 5 minutes, take the supernatant and filter it through a 0.45μm filter membrane, discard 1ml of the initial filtrate, and take the subsequent filtrate as the sample solution.

[0049] Step six, respectively detecting the atropine sulfate control solution and the sample solution by high performance liquid chromatography;

[0050] Table 1: Chromatographic conditions:

[0051]

[0052] Table 2: Injection sequence:

[0053] Perform sample analysis according to the injection sequence in the table below.

[0054]

[0055]

[0056] Note:

[0057] Compare the chromatograms of the solvent blank solution, sample solution and atropine sulfate control solution. There should be no obvious interference at the retention time position of atropine sulfate.

[0058] Table 3: System suitability test results:

[0059]

[0060] Among them, it should be noted that

[0061] Inject at least one injection of blank solution, five injections of atropine sulfate reference substance 1, and one injection of atropine sulfate reference substance 2;

[0062] The acceptable criteria for the system suitability experiment results are that the blank solvent has no obvious interference at the retention time position of the atropine sulfate peak; the RSD value of the area of ​​the peak of atropine sulfate reference substance 1 after 5 consecutive injections is no more than 5%; and the recovery rate of atropine sulfate reference substance 2 relative to atropine sulfate reference substance 1 is within the range of 95% to 105%.

[0063] Table 4: Determination results of atropine sulfate content in compound sodium hydroxide aluminum tablets according to the determination method in the embodiment:

[0064]

[0065]

[0066] It should be noted that the RSD value of the atropine sulfate content in the 6 samples of compound sodium hydroxide aluminum tablets should not be greater than 5%.

[0067] The following is the calculation formula:

[0068]

[0069] Where: Sa: peak area of ​​sample; Mt: weight of reference substance, g;

[0070] St: peak area of ​​reference substance; m: weight of sample, g;

[0071] P: purity of the reference substance; M: average tablet weight, g;

[0072] In summary, the chromatographic conditions and related analytical methods determined in the present invention have many beneficial effects such as high efficiency, accuracy and reliability in the determination of the content of atropine sulfate in the compound aluminum hydroxide tablets, and have important practical significance and application value for improving the quality control level of drugs.

[0073] The above description is only a preferred embodiment of the present invention, and does not limit the implementation mode and protection scope of the present invention. For those skilled in the art, it should be aware that all solutions obtained by equivalent substitutions and obvious changes made using the description and illustrations of the present invention should be included in the protection scope of the present invention.

Claims

1. A method for determining the content of atropine sulfate in a composite aluminum hydroxide tablet, characterized in that: The following steps are involved: Step 1, providing potassium dihydrogen phosphate, sodium 1-pentane sulfonate, phosphoric acid, acetonitrile, hydrochloric acid, atropine sulfate, and aluminum hydroxide; Step 2, mixing and dissolving the potassium dihydrogen phosphate and the sodium 1-pentane sulfonate in pure water to obtain a mixed solution; The mixed solution is adjusted to pH 2.5±0.05 with the phosphoric acid, and filtered to obtain a buffer solution; Step 3, The buffer solution and the acetonitrile are sequentially mixed in a ratio of 17:1-3, and ultrasonically degassed to obtain mobile phase A; the buffer solution and the acetonitrile are sequentially mixed in a ratio of 1-3:7-9, and ultrasonically degassed to obtain mobile phase B; Step 4, weighing the atropine sulfate, dissolving and diluting the atropine sulfate in sequence to obtain an atropine sulfate control solution; Step 5, weighing the composite aluminum hydroxide tablets, adding hydrochloric acid solution, diluting to scale with the buffer solution, centrifuging, and filtering to obtain a sample solution; Step six, respectively detecting the atropine sulfate control solution and the sample solution by high performance liquid chromatography.

2. The method for determining the content of atropine sulfate in a composite aluminum hydroxide tablet according to claim 1, characterized in that: In the step 1, the mass ratio of the potassium dihydrogen phosphate and the sodium 1-pentane sulfonate when mixed is 17-19:24-26.

3. The method for determining the content of atropine sulfate in a composite aluminum hydroxide tablet according to claim 1, characterized in that: The concentration of the atropine sulfate control solution is 4. The method for determining the content of atropine sulfate in a composite aluminum hydroxide tablet according to claim 1, characterized in that: In the step five, 1 unit mass of the aluminum hydroxide is added to 20-30 unit volumes of the hydrochloric acid solution; Wherein, the concentration of the hydrochloric acid solution is 0.5mol / L-2mol / L.

5. The method for determining the content of atropine sulfate in a composite aluminum hydroxide tablet according to claim 1, characterized in that: In the step six, the chromatographic column used in the high performance liquid chromatography is a reverse phase C18 column, and the column temperature of the chromatographic column during injection is 50° C.-40° C.

6. The method for determining the content of atropine sulfate in a composite aluminum hydroxide tablet according to claim 1, characterized in that: In step six, the detector used in the high performance liquid chromatography is an ultraviolet detector, and the detection wavelength of the ultraviolet detector is 200nm-220nm.

7. The method for determining the content of atropine sulfate in a composite aluminum hydroxide tablet according to claim 1, characterized in that: In the step six, the flow rate of the mobile phase in the high performance liquid chromatography is 1 mL / min-3 mL / min, and the injection volume of the sample solution is 90 μL-110 μL.

8. The method for determining the content of atropine sulfate in a composite aluminum hydroxide tablet according to claim 1, characterized in that: The high performance liquid chromatography detection adopts gradient elution, and the gradient elution process is as follows: At 11 min, the volume fraction of mobile phase A decreased from 92% to 79%, and the volume fraction of mobile phase B increased from 8% to 21%; 11min-15min: the volume fraction of mobile phase A decreased from 97% to 46%, and the volume fraction of mobile phase B increased from 21% to 54%; 15min-15.1min: the volume fraction of mobile phase A increased from 46% to 92%, and the volume fraction of mobile phase B decreased from 54% to 8%; 15.1min-20min: the volume fraction of mobile phase A is maintained at 92%, and the volume fraction of mobile phase B is maintained at 8%; The post-run time of mobile phase A and mobile phase B is 1 min-5 min.

Images