Buspirone hydrochloride content detection method

Abstract

The invention belongs to the technical field of pharmaceutical analysis, and particularly relates to a buspirone hydrochloride content detection method, which adopts a high performance liquid chromatography under the chromatographic conditions that a mobile phase is a methanol-phosphate buffer solution, a chromatographic column is a C18 reversed-phase column, the detection wavelength is 239-249 nm, the column temperature is 30-40 DEG C, the flow velocity is 0.8 mL / min-1. 2 mL / min, the column temperature is 30-40 DEG C, the column temperature is 30-40 DEG C, the column temperature is 30-40 DEG C, the column temperature is 30-40 DEG C, the column temperature is 30-40 DEG C, the column temperature is 30-40 DEG C, and the the sample is diluted into a solution containing 0.005 mg / mL-0. 15 mg / mL of buspirone hydrochloride, and the sample comprises a raw material medicine and a preparation. The method for measuring buspirone hydrochloride through the high performance liquid chromatography can be used for detecting the content of active ingredients in the buspirone hydrochloride raw material medicine and the preparation at the same time; the detection is rapid, the result is accurate, and the repeatability is good.

Description

Technical Field

[0001] The invention belongs to the technical field of drug analysis, and particularly relates to a method for detecting the content of buspirone hydrochloride. Background Art

[0002] High-Performance Liquid Chromatography (HPLC), also known as "high-pressure liquid chromatography," "high-speed liquid chromatography," "high-resolution liquid chromatography," and "modern column chromatography," is a key branch of chromatography. Using a liquid as the mobile phase, a high-pressure infusion system pumps a single solvent of varying polarity, or mixed solvents of varying proportions, buffers, and other mobile phases through a chromatographic column containing a stationary phase. After the components are separated within the column, they are detected by a detector, enabling analysis of the sample. This method has become an important separation and analysis technique in disciplines such as chemistry, medicine, industry, agronomy, commercial inspection, and legal inspection.

[0003] Buspirone hydrochloride is an organic compound with the chemical formula C 21 H 32 ClN₅O₂ is an antianxiety drug primarily used to treat various anxiety disorders, depression, maladaptive behaviors, and as an adjunct to obsessive-compulsive disorder. Buspirone hydrochloride is currently determined by chromogenic titration, UV spectrophotometry, and HPLC. However, these existing methods have the following drawbacks: UV spectrophotometry suffers from poor specificity and is susceptible to interference from excipients; chromogenic titration is not conducive to endpoint determination; and the HPLC method has a long run time. Summary of the Invention

[0004] In order to solve the problems in the prior art, the present invention provides a method for detecting the content of buspirone hydrochloride, which adopts high performance liquid chromatography (HPLC) to determine the content of active ingredients in buspirone hydrochloride raw materials and preparations, achieving the purpose of rapid, accurate and reproducible determination.

[0005] The present invention solves the technical problem by adopting the following technical solutions:

[0006] The present invention aims to provide a method for detecting the content of buspirone hydrochloride, which adopts high performance liquid chromatography, and the chromatographic conditions are as follows: mobile phase: methanol-phosphate buffer, chromatographic column: C18 reverse phase column, detection wavelength: 239nm-249nm, column temperature: 30℃-40℃, flow rate: 0.8mL / min-1.2mL / min.

[0007] Furthermore, the pH of the methanol-phosphate buffer is 3.5±0.1.

[0008] Furthermore, the phosphate buffer is 0.05 mol / L-0.07 mol / L potassium dihydrogen phosphate.

[0009] Furthermore, methanol-potassium dihydrogen phosphate=60:40.

[0010] Furthermore, the method also includes processing of samples before testing: diluting the sample into a solution containing 0.005 mg / mL-0.15 mg / mL of buspirone hydrochloride, and the sample includes raw materials and preparations.

[0011] Furthermore, the processing of the raw material drug sample includes: dissolving the sample with a 0.07 mol / L-0.13 mol / L hydrochloric acid solution and diluting it to a solution containing 0.005 mg / mL-0.15 mg / mL of buspirone hydrochloride.

[0012] Furthermore, the preparation sample treatment includes: adding 2mL-5mL of methanol to the sample for infiltration and disintegration, adding 0.07mol / L-0.13mol / L hydrochloric acid solution as a diluent, ultrasonic extraction for 10 minutes to 30 minutes, centrifugal filtration, and dilution to a solution containing 0.005mg / mL-0.15mg / mL of buspirone hydrochloride.

[0013] Furthermore, the centrifugal speed is 8000 rpm-12000 rpm.

[0014] Compared with the prior art, the beneficial technical effects of the present invention are:

[0015] 1. The method of the present invention can be used for detecting the content of active ingredients in buspirone hydrochloride raw materials and preparations at the same time, and the detection is rapid, the results are accurate, and the repeatability is good.

[0016] 2. The analysis time using the method of the present invention is shortened to within 8 minutes, which is 80% more efficient than the existing HPLC method.

[0017] 3. In the process of determining the active ingredient content in the preparation by the method of the present invention, 5 ml of methanol is first added to infiltrate and disintegrate the preparation to avoid agglomeration of the excipients during the extraction process, which may affect the extraction of the active ingredient.

[0018] The above description is only an overview of the technical solution of the present invention. In order to more clearly understand the technical means of the present invention, it can be implemented in accordance with the contents of the specification. In order to make the above contents of the present invention and its objectives, features and advantages more obvious and easy to understand, the specific implementation methods of the present invention are specifically listed below. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 The chromatogram of the reference substance in the present invention (displaying the number of theoretical plates>5000).

[0020] Figure 2The chromatogram shows the separation degree between the active ingredient and the impurities in the present invention (the separation degree between the main peak and the impurities is greater than 1.8). DETAILED DESCRIPTION

[0021] The technical solutions of the present invention are further described in detail below with reference to specific embodiments. It should be understood that the following embodiments are merely illustrative and explain 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 encompassed within the scope that the present invention is intended to protect.

[0022] In addition, unless otherwise specified, various raw materials, reagents, instruments and equipment used in the present invention can be purchased from the market or prepared by existing methods.

[0023] Example 1

[0024] A rapid, accurate, and reproducible HPLC method for the detection of buspirone hydrochloride comprises:

[0025] 1. Sample processing:

[0026] - API: After accurately weighing, dissolve in 0.07 mol / L hydrochloric acid solution and dilute to a solution containing 0.005 mg / mL of buspirone hydrochloride.

[0027] - Preparation: After ultrasonic extraction (2 mL of methanol for infiltration and disintegration, 0.07 mol / L hydrochloric acid solution as diluent, for 10 minutes), centrifugation (8000 rpm) and filtration, the solution was diluted to a concentration of 0.005 mg / mL of buspirone hydrochloride.

[0028] 2. Chromatographic conditions:

[0029] -Mobile phase: methanol-phosphate buffer (pH 3.4) (60:40, v / v);

[0030] -Chromatographic column: C18 reverse phase column (250×4.6 mm, 5 μm);

[0031] - Detection wavelength: 239nm;

[0032] - Column temperature: 30°C;

[0033] -Flow rate: 0.8 mL / min.

[0034] Example 2

[0035] A rapid, accurate, and reproducible HPLC method for the detection of buspirone hydrochloride comprises:

[0036] 1. Sample processing:

[0037] - API: After accurately weighing, dissolve in 0.13 mol / L hydrochloric acid solution and dilute to a solution containing 0.15 mg / mL of buspirone hydrochloride.

[0038] - Preparation: After ultrasonic extraction (5 mL of methanol for infiltration and disintegration, 0.13 mol / L hydrochloric acid solution as diluent, for 30 minutes), centrifugation (12000 rpm) and filtration, the solution was diluted to a concentration of 0.15 mg / mL of buspirone hydrochloride.

[0039] 2. Chromatographic conditions:

[0040] -Mobile phase: methanol-phosphate buffer (pH 3.6) (60:40, v / v);

[0041] -Chromatographic column: C18 reverse phase column (250×4.6 mm, 5 μm);

[0042] - Detection wavelength: 249nm;

[0043] - Column temperature: 40°C;

[0044] -Flow rate: 1.2 mL / min.

[0045] Example 3

[0046] A rapid, accurate, and reproducible HPLC method for the detection of buspirone hydrochloride comprises:

[0047] 1. Sample processing:

[0048] - API: After accurately weighing, dissolve in 0.1 mol / L hydrochloric acid solution and dilute to a solution containing 0.05 mg / mL of buspirone hydrochloride.

[0049] - Preparation: After ultrasonic extraction (4 mL of methanol for infiltration and disintegration, 0.1 mol / L hydrochloric acid solution as diluent, for 20 minutes), centrifugation (10,000 rpm) and filtration, the solution was diluted to a concentration of 0.05 mg / mL of buspirone hydrochloride.

[0050] 2. Chromatographic conditions:

[0051] -Mobile phase: methanol-phosphate buffer (pH 3.5) (60:40, v / v);

[0052] -Chromatographic column: C18 reverse phase column (250×4.6 mm, 5 μm);

[0053] - Detection wavelength: 244nm;

[0054] - Column temperature: 35°C;

[0055] -Flow rate: 1.0 mL / min.

[0056] Test Example 1: Determination of API Content

[0057] 1. Solvent: 0.1 mol / L hydrochloric acid (take 9 ml of hydrochloric acid, add it to 1000 ml of water, and stir well).

[0058] 2. Reference solution: Accurately weigh 25 mg of buspirone hydrochloride reference substance, place in a 50 ml volumetric flask, add an appropriate amount of 0.1 mol / L hydrochloric acid, dissolve and dilute to the scale, shake well, filter, take 1 ml of the filtrate, place in a 10 ml volumetric flask, add 0.1 mol / L hydrochloric acid to dilute to the scale, and shake well.

[0059] 3. Test solution (i.e., sample solution): Accurately weigh 25 mg of buspirone hydrochloride raw material, place it in a 50 ml volumetric flask, add an appropriate amount of 0.1 mol / L hydrochloric acid, dissolve and dilute to the scale, shake well, filter, take 1 ml of the filtrate, place it in a 10 ml volumetric flask, add 0.1 mol / L hydrochloric acid to dilute to the scale, and shake well.

[0060] 4. The test results are shown in Table 1 below:

[0061] Table 1

[0062]

[0063] Result analysis: The requirement is that the RSD of 5 samples should be less than 2%, and the content should be between 98.0% and 102.0%. The results are in compliance with the requirements. This method is highly accurate in determining the content of raw materials.

[0064] Test Example 2: Tablet Content Uniformity Determination

[0065] 1. Solvent: 0.1 mol / L hydrochloric acid (take 9 ml of hydrochloric acid, add it to 1000 ml of water, and stir well).

[0066] 2. Reference solution: Accurately weigh 25 mg of buspirone hydrochloride reference substance, place in a 50 ml volumetric flask, add an appropriate amount of 0.1 mol / L hydrochloric acid, dissolve and dilute to the scale, shake well, filter, take 1 ml of the filtrate, place in a 10 ml volumetric flask, add 0.1 mol / L hydrochloric acid to dilute to the scale, and shake well.

[0067] 3. Test solution: Take one buspirone hydrochloride sustained-release tablet (containing 20 mg of the main ingredient / tablet), place it in a 50 ml volumetric flask, add 5 ml of methanol and ultrasonically disintegrate the tablet, then add an appropriate amount of 0.1 mol / L hydrochloric acid, ultrasonically extract for 15 minutes, let cool, add solvent to dilute to the scale, shake well, centrifuge (10000 rpm), take the supernatant and filter, take 1 ml of the filtrate, place it in a 10 ml volumetric flask, add 0.1 mol / L hydrochloric acid to dilute to the scale, shake well (parallel 10 tablets).

[0068] 4. The results are shown in Table 2 below.

[0069] Table 2

[0070]

[0071] Result analysis: The requirement for single tablet content is 95.0% to 105.0%, and A+2.2S≤15. The test results all meet the requirements. This method is highly accurate in determining tablet content uniformity.

[0072] Comparative Example 1: Determination of the contents of three batches of preparations by UV spectrophotometry and the method of the present invention

[0073] 1. Ultraviolet spectrophotometry (UV method):

[0074] (1) Reference solution: Take an appropriate amount of buspirone hydrochloride reference substance, accurately weigh it, dissolve it in 0.1 mol / L hydrochloric acid solution and quantitatively dilute it to make a solution containing approximately 10 μg per 1 ml.

[0075] (2) Test solution: Take 20 tablets of this product, accurately weigh them, grind them into powder, accurately weigh an appropriate amount (equivalent to 10 mg of buspirone hydrochloride), place it in a 100 ml volumetric flask, add 0.1 mol / L hydrochloric acid solution to dissolve and dilute to the scale, shake well, filter, accurately measure 5 ml of the filtrate, place it in a 50 ml volumetric flask, dilute to the scale with 0.1 mol / L hydrochloric acid solution, and shake well.

[0076] (3) Determination: Take the test solution and the reference solution, measure the absorbance at a wavelength of 233 nm, and calculate.

[0077] 2. The method of the present invention (HPLC method):

[0078] (1) Solvent: 0.1 mol / L hydrochloric acid.

[0079] (2) Reference solution: Accurately weigh 25 mg of buspirone hydrochloride reference solution, place in a 50 ml volumetric flask, add an appropriate amount of 0.1 mol / L hydrochloric acid, dissolve and dilute to the mark, shake well, filter, take 1 ml of the filtrate, place in a 10 ml volumetric flask, add 0.1 mol / L hydrochloric acid to dilute to the mark, shake well.

[0080] (3) Test solution: Take 20 tablets of this product, accurately weigh them, grind them into powder, accurately weigh an appropriate amount (equivalent to 25 mg of buspirone hydrochloride), place them in a 50 ml volumetric flask, add 5 ml of methanol and ultrasonically disintegrate the tablets, then add an appropriate amount of 0.1 mol / L hydrochloric acid, ultrasonically extract for 15 min, let it cool, add solvent to dilute to the scale, shake well, centrifuge (10,000 rpm), take the supernatant and filter, take 1 ml of the filtrate, place it in a 10 ml volumetric flask, add 0.1 mol / L hydrochloric acid to dilute to the scale, shake well.

[0081] (4) Determination: Chromatographic column with octadecylsilane bonded silica as filler (C18 reverse phase chromatography column); mobile phase, methanol-0.06 mol / L potassium dihydrogen phosphate (pH adjusted to 3.5 with phosphoric acid) = 60:40; column temperature: 35°C; flow rate: 1.0 ml / min; wavelength: 244 nm; injection volume: 20 μl.

[0082] 3. Take three batches of this product for testing (241001, 241002, 241101)

[0083] The results are shown in Table 3:

[0084] Table 3

[0085]

[0086] Result analysis: The accuracy of the method of the present invention (HPLC method) is significantly better than that of the UV method.

[0087] Use the method of the present invention to verify:

[0088] -Linear range 0.005-0.15 mg / mL (r=0.9998);

[0089] - Repeatability RSD < 0.5% (n = 6);

[0090] - Recovery rate 98.5%-101.2%;

[0091] Tolerance tests showed that when the pH fluctuated by ±0.5, the retention time changed by less than 1%.

[0092] The serial numbers of the above embodiments of the present invention are for description only and do not represent the advantages or disadvantages of the embodiments.

[0093] The embodiments of the present invention are described above in conjunction with the accompanying drawings, but the present invention is not limited to the above-mentioned specific implementation methods. The above-mentioned specific implementation methods are merely illustrative and not restrictive. Under the guidance of the present invention, ordinary technicians in this field can also make many forms without departing from the scope of protection of the present invention and the claims, all of which are protected by the present invention.

Claims

1. A method for detecting the content of buspirone hydrochloride, characterized in that: High performance liquid chromatography was used, and the chromatographic conditions were as follows: mobile phase: methanol-phosphate buffer, chromatographic column: C18 reverse phase column, detection wavelength: 239 nm-249 nm, column temperature: 30°C-40°C, flow rate: 0.8 mL / min-1.2 mL / min.

2. A method for detecting buspirone hydrochloride content as claimed in claim 1, characterized in that: The pH of the methanol-phosphate buffer was 3.5 ± 0.

1.

3. A method for detecting buspirone hydrochloride content as claimed in claim 2, characterized in that: The phosphate buffer is 0.05mol / L-0.07mol / L potassium dihydrogen phosphate.

4. A method for detecting buspirone hydrochloride content as claimed in claim 1, characterized in that: It also includes sample processing before testing: diluting the sample into a solution containing 0.005 mg / mL-0.15 mg / mL of buspirone hydrochloride, and the sample includes raw materials or preparations.

5. A method for detecting buspirone hydrochloride content as claimed in claim 4, characterized in that: The processing of the raw material drug sample includes: dissolving the sample with 0.07mol / L-0.13mol / L hydrochloric acid solution and diluting it to a solution containing 0.005mg / mL-0.15mg / mL of buspirone hydrochloride.

6. A method for detecting buspirone hydrochloride content as claimed in claim 4, characterized in that: The treatment of the preparation sample includes: adding 2mL-5mL of methanol to the sample for infiltration and disintegration, then adding 0.07mol / L-0.13mol / L hydrochloric acid solution as a diluent, ultrasonic extraction for 10 minutes-30 minutes, centrifugal filtration, and dilution to a solution containing 0.005mg / mL-0.15mg / mL of buspirone hydrochloride.

7. A method for detecting buspirone hydrochloride content as claimed in claim 6, characterized in that: The centrifugal speed is 8000 rpm-12000 rpm.

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