CN113820427A - Method for determining pramipexole dihydrochloride content in pramipexole dihydrochloride sustained-release tablets - Google Patents
Method for determining pramipexole dihydrochloride content in pramipexole dihydrochloride sustained-release tablets Download PDFInfo
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Abstract
The invention relates to a method for measuring the pramipexole dihydrochloride content in a pramipexole dihydrochloride sustained-release tablet, which comprises the following steps: mixing the sustained-release tablet to be detected with a diluent, performing ultrasonic treatment, detecting the solution by adopting a liquid chromatography, and calculating by using an external standard method to obtain the content of pramipexole dihydrochloride; the diluent is a methanol solution containing trifluoroacetic acid. The methanol solution containing trifluoroacetic acid is creatively used as a diluent to be mixed with the pramipexole dihydrochloride sustained-release tablets to be detected, the sustained-release tablets are disintegrated in the diluent by matching with ultrasound, the medicine is fully released, the problems that the tablets are not easy to disintegrate and easily absorb active ingredients due to the fact that the hydroxypropyl methylcellulose and the like easily form a colloidal solution in water at room temperature are solved, the detection result of the subsequent liquid chromatography is more accurate, and the method has high accuracy, precision and sensitivity; good linearity, specificity and system adaptability.
Description
Technical Field
The invention belongs to the technical field of drug analysis, and particularly relates to a method for determining pramipexole dihydrochloride content in pramipexole dihydrochloride sustained-release tablets.
Background
Pramipexole dihydrochloride sustained release tablets are used for treating signs and symptoms of idiopathic parkinsonism. The Chinese pharmacopoeia and other pharmacopoeias of various countries have no chapter for recording pramipexole dihydrochloride sustained-release tablets. For the content determination of the raw material drug pramipexole dihydrochloride, all extraction solvents used in pharmacopoeia of various countries are organic solvents and phosphate buffer solutions. The pramipexole hydrochloride is easy to dissolve in water, dissolve in methanol and slightly dissolve in ethanol, and the adoption of an organic solvent and a phosphate buffer solution as extraction solvents is suitable for measuring the content of the pramipexole hydrochloride serving as a raw material drug.
Therefore, it is very necessary to provide an analysis method for measuring the pramipexole dihydrochloride content in the pramipexole dihydrochloride sustained-release tablets, which has the advantages of rapid analysis, strong anti-interference performance and high sensitivity.
Disclosure of Invention
Aiming at the defects of the prior art, the invention aims to provide a method for measuring the pramipexole dihydrochloride content in a pramipexole dihydrochloride sustained-release tablet.
In order to achieve the purpose, the invention adopts the following technical scheme:
in a first aspect, the present invention provides a method for determining pramipexole dihydrochloride content in a pramipexole dihydrochloride sustained release tablet, where the method for determining pramipexole dihydrochloride content in the pramipexole dihydrochloride sustained release tablet includes:
mixing the sustained-release tablet to be detected with a diluent, performing ultrasonic treatment, detecting the solution by adopting a liquid chromatography, and calculating by using an external standard method to obtain the content of pramipexole dihydrochloride; the diluent is a methanol solution containing trifluoroacetic acid.
The methanol solution containing trifluoroacetic acid is creatively used as a diluent to be mixed with the pramipexole dihydrochloride sustained-release tablets to be detected, the sustained-release tablets are disintegrated in the diluent by matching with ultrasound, the medicine is fully released, the problems that the tablets are not easy to disintegrate and easily absorb active ingredients due to the fact that the hydroxypropyl methylcellulose and the like easily form a colloidal solution in water at room temperature are solved, the detection result of the subsequent liquid chromatography is more accurate, and the method has high accuracy, precision and sensitivity; good linearity, specificity and system adaptability.
Preferably, the concentration of trifluoroacetic acid in the diluent is 0.5-1.5%, such as 0.5%, 0.6%, 0.7%, 0.8%, 0.9%, 1.0%, 1.1%, 1.2%, 1.3%, 1.4%, 1.5%, etc., and other specific values in the numerical range can be selected, which is not described in detail herein.
The concentration of the trifluoroacetic acid is specially limited to 0.5-1.5%, because the concentration can not influence the subsequent liquid phase detection result as a test solution, and can ensure that the active ingredients in the sustained-release tablet are fully released, so that the final detection result has higher accuracy and precision, and better linearity and system adaptability.
Preferably, the diluent also contains hydrochloric acid.
The methanol solution containing trifluoroacetic acid and hydrochloric acid is more preferably used as a diluent, so that the final detection result has higher accuracy and precision, and better linearity and system adaptability.
Preferably, the mass ratio of the hydrochloric acid to the trifluoroacetic acid is 1 (2-10), for example, 1:2, 1:2.5, 1:3, 1:3.5, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, and the like, and other specific values in the numerical range can be selected, which is not described herein again.
Preferably, the sustained release tablet to be tested is completely disintegrated by ultrasonic wave.
Preferably, the stationary phase in the liquid chromatography is an octadecylsilane bonded silica gel column.
Preferably, the mobile phase in the liquid chromatography comprises a phase A and a phase B, wherein the phase A is a mixed solution of methanol and a phosphate buffer solution, and the phase B is acetonitrile.
The invention creatively uses the A phase (the mixed solution of methanol and phosphate buffer solution) and the B phase (acetonitrile) as the mobile phase of liquid phase detection, wherein the methanol is helpful for enhancing the elution capacity of the chromatographic column and improving the peak shape of a chromatographic peak, the phosphate buffer solution is helpful for improving the peak shape and ensuring the reproducibility of the chromatographic peak, and the accuracy, the precision, the linearity and the system adaptability of the final detection result are higher under the condition of the mobile phase.
Preferably, the pH of the phosphate buffer is 2.5-3.5, for example, pH 2.5, pH 2.6, pH 2.7, pH 2.8, pH 2.9, pH 3.0, pH 3.1, pH 3.2, pH 3.3, pH 3.4, pH 3.5, and the like, and specific values within the range may be selected, which is not repeated herein.
The specific selection of the pH value of the phosphate buffer solution is 2.5-3.5 because the chromatographic peak has poor shape if the pH value is further increased, and the chromatographic peak has low reproducibility if the pH value is further reduced, and is easy to damage chromatographic columns and reduce the service life.
Preferably, the volume ratio of the phosphate buffer solution to the methanol is (5-10):1, for example, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, etc., and other specific values within the numerical range can be selected, which is not described in detail herein.
Preferably, the preparation method of the phosphate buffer solution comprises the following steps:
mixing potassium dihydrogen phosphate, sodium octane sulfonate and water in a mass ratio of (1-2):1 (100-), (300), adjusting the pH value to 2.5-3.5 by using phosphoric acid or sodium hydroxide, and shaking up.
The above-mentioned (1-2):1: (100) — (300) may be, for example, 1:1:100, 1:1:150, 1:1:200, 1:1:250, 1:1:300, 2:1:100, 2:1:150, 2:1:200, 2:1:250, 2:1:300, etc., and other specific values within the numerical range may be selected, which is not described herein again.
Preferably, the liquid chromatography uses a gradient elution mode, and the gradient elution is carried out to the following extent: 0min, 70-90% of phase A and 10-30% of phase B; 15min, 50-70% of phase A and 30-50% of phase B; 16min, 70-90% of phase A and 10-30% of phase B; 20min, 70-90% of phase A and 10-30% of phase B.
The invention preferably selects the specific gradient elution mode, and the accuracy, precision and sensitivity of the detection result are higher in the elution mode; the linearity, specificity and system adaptability are better.
Preferably, the detection wavelength is 262-266nm, such as 262nm, 263nm, 264nm, 265nm, 266nm and the like, in the liquid chromatography; the column temperature is 35-45 deg.C, such as 35 deg.C, 36 deg.C, 37 deg.C, 38 deg.C, 40 deg.C, 42 deg.C, 43 deg.C, 45 deg.C, etc. Other specific point values within the above numerical range can be selected, and are not described in detail herein.
Preferably, the flow rate in the liquid chromatography is 1.0-2.0mL/min, such as 1.0mL/min, 1.2mL/min, 1.3mL/min, 1.4mL/min, 1.5mL/min, 1.6mL/min, 1.7mL/min, 1.8mL/min, 2.0mL/min, and the like; the injection volume is 5-25. mu.L, such as 5. mu.L, 10. mu.L, 15. mu.L, 20. mu.L, 25. mu.L, etc. Other specific point values within the above numerical range can be selected, and are not described in detail herein.
Compared with the prior art, the invention has the following beneficial effects:
the methanol solution containing trifluoroacetic acid is creatively used as a diluent to be mixed with the pramipexole dihydrochloride sustained-release tablets to be detected, the sustained-release tablets are disintegrated in the diluent by matching with ultrasound, the medicine is fully released, the problems that the tablets are not easy to disintegrate and easily absorb active ingredients due to the fact that the hydroxypropyl methylcellulose and the like easily form a colloidal solution in water at room temperature are solved, the detection result of the subsequent liquid chromatography is more accurate, and the method has high accuracy, precision and sensitivity; good linearity, specificity and system adaptability.
Drawings
FIG. 1 is a chromatogram of a solvent blank solution;
FIG. 2 is a chromatogram of a control;
FIG. 3 is a chromatogram of the test article of example 1;
FIG. 4 is a chromatogram of the test article of example 2;
FIG. 5 is a chromatogram of the test article of example 5;
FIG. 6 is a chromatogram of the test sample of example 6.
Detailed Description
The technical solution of the present invention is further explained by the following embodiments. It should be understood by those skilled in the art that the examples are only for the understanding of the present invention and should not be construed as the specific limitations of the present invention.
Example 1
This example provides a method for determining pramipexole dihydrochloride content in a pramipexole dihydrochloride sustained-release tablet (specification: 0.375mg, the theoretical pramipexole dihydrochloride content in the tablet is 0.375mg, which is 0.16% of the total tablet weight), which is performed as follows:
(1) preparation of phosphate buffered saline solution with pH 3.0:
weighing 18.2g of monopotassium phosphate and 10g of sodium octane sulfonate, dissolving in 2L of water, adjusting the pH value to 3.0, and shaking up;
(2) preparation of a mobile phase:
mobile phase A: respectively measuring 100mL of anhydrous methanol and 700mL of the phosphate buffer solution, uniformly mixing, and filtering by using a 0.45-micron organic filter membrane;
mobile phase B: measuring acetonitrile, and filtering with 0.45 μm organic filter membrane;
(3) preparing a diluent:
measuring 10mL of trifluoroacetic acid, putting the trifluoroacetic acid in 1000mL of methanol, and uniformly mixing;
(4) preparing a test solution:
transferring 5 pramipexole dihydrochloride sustained-release tablets into a 200mL measuring flask, adding 160mL diluent into the measuring flask, performing ultrasonic treatment for 30min to completely disintegrate the sustained-release tablets, cooling to 25 ℃, performing constant volume to scale with the diluent, centrifuging part of the solution at 15000rpm for 5min, and taking the supernatant as a sample for liquid phase analysis;
(5) preparing a reference substance solution:
accurately weighing 20mg to 100mL of pramipexole dihydrochloride standard substance in a measuring flask, dissolving the pramipexole dihydrochloride standard substance by using a diluent to fix the volume to a scale, wherein the solution is a reference substance stock solution. Measuring the reference substance storage solution in a measuring flask of 5-100 mL, diluting to scale with diluent, and analyzing as reference substance liquid phase;
(6) liquid phase conditions:
liquid phase chromatograph: an Agilent 1200 chromatographic system and workstation;
a chromatographic column: sunfire C18, Vortight, 4.6X 150 mm;
flow rate: 1.5 mL/min;
detection wavelength: UV 264 nm;
sample introduction volume: 10 mu L of the solution;
column temperature: 40 ℃;
analysis time: 20 min;
elution gradient:
FIG. 1 is a chromatogram of a solvent blank solution; FIG. 2 is a chromatogram of a control; FIG. 3 is a chromatogram of a sample.
The methodology of the method is examined, and comprises the following steps: accuracy (recovery), precision, detection limit, linearity, specificity, system adaptability.
Example 2
This example provides a method for measuring pramipexole dihydrochloride sustained release tablets (specification: 0.75mg, the theoretical pramipexole dihydrochloride content in the tablet is 0.75mg, which is 0.33% of the total tablet weight), which is performed as follows:
(1) preparation of phosphate buffered saline solution with pH 3.2:
weighing 18.2g of monopotassium phosphate and 10g of sodium octane sulfonate, dissolving in 2L of water, adjusting the pH value to 3.2, and shaking up;
(2) preparation of a mobile phase:
mobile phase A: respectively measuring 100mL of anhydrous methanol and 900mL of the phosphate buffer solution, uniformly mixing, and filtering by using a 0.45-micron organic filter membrane;
mobile phase B: measuring acetonitrile, and filtering with 0.45 μm organic filter membrane;
(3) preparing a diluent:
measuring 13mL of trifluoroacetic acid, putting the trifluoroacetic acid in 1000mL of methanol, and uniformly mixing;
(4) preparing a test solution:
transferring 5 pramipexole dihydrochloride sustained-release tablets into a 200mL measuring flask, adding 160mL diluent into the measuring flask, performing ultrasonic treatment for 30min to completely disintegrate the sustained-release tablets, cooling to 25 ℃, performing constant volume to scale with the diluent, centrifuging part of the solution at 15000rpm for 5min, and taking the supernatant as a sample for liquid phase analysis;
(5) preparing a reference substance solution:
accurately weighing 20mg to 100mL of pramipexole dihydrochloride standard substance in a measuring flask, dissolving the pramipexole dihydrochloride standard substance by using a diluent to fix the volume to a scale, wherein the solution is a reference substance stock solution. Measuring the reference substance storage solution in a measuring flask of 5-100 mL, diluting to scale with diluent, and analyzing as reference substance liquid phase;
(6) liquid phase conditions:
liquid phase chromatograph: an Agilent 1200 chromatographic system and workstation;
a chromatographic column: sunfire C18, Vortight, 4.6X 150 mm;
flow rate: 1.0 mL/min;
detection wavelength: UV 264 nm;
sample introduction volume: 15 mu L of the solution;
column temperature: 42 ℃;
analysis time: 20 min;
elution gradient:
FIG. 4 is a chromatogram of a sample.
The methodology of the method is examined, and comprises the following steps: accuracy (recovery), precision, detection limit, linearity, specificity, system adaptability.
Example 3
This example provides a method for measuring pramipexole dihydrochloride sustained release tablets (specification: 0.75mg, the theoretical pramipexole dihydrochloride content in the tablet is 0.75mg, which is 0.33% of the total tablet weight), which is performed as follows:
(1) preparation of phosphate buffered saline solution with pH 2.8:
weighing 18.2g of monopotassium phosphate and 10g of sodium octane sulfonate, dissolving in 2L of water, adjusting the pH value to 2.8, and shaking up;
(2) preparation of a mobile phase:
mobile phase A: respectively measuring 100mL of anhydrous methanol and 600mL of the phosphate buffer solution, uniformly mixing, and filtering by using a 0.45-micron organic filter membrane;
mobile phase B: measuring acetonitrile, and filtering with 0.45 μm organic filter membrane;
(3) preparing a diluent:
measuring 8mL of trifluoroacetic acid, putting the trifluoroacetic acid in 1000mL of methanol, and uniformly mixing;
(4) preparing a test solution:
transferring 5 pramipexole dihydrochloride sustained-release tablets into a 200mL measuring flask, adding 160mL diluent into the measuring flask, performing ultrasonic treatment for 30min to completely disintegrate the sustained-release tablets, cooling to 25 ℃, performing constant volume to scale with the diluent, centrifuging part of the solution at 15000rpm for 5min, and taking the supernatant as a sample for liquid phase analysis;
(5) preparing a reference substance solution:
accurately weighing 20mg to 100mL of pramipexole dihydrochloride standard substance in a measuring flask, dissolving the pramipexole dihydrochloride standard substance by using a diluent to fix the volume to a scale, wherein the solution is a reference substance stock solution. Measuring the reference substance storage solution in a measuring flask of 5-100 mL, diluting to scale with diluent, and analyzing as reference substance liquid phase;
(6) liquid phase conditions:
liquid phase chromatograph: an Agilent 1200 chromatographic system and workstation;
a chromatographic column: sunfire C18, Vortight, 4.6X 150 mm;
flow rate: 1.8 mL/min;
detection wavelength: UV 264 nm;
sample introduction volume: 10 mu L of the solution;
column temperature: 37 ℃;
analysis time: 20 min;
elution gradient:
the methodology of the method is examined, and comprises the following steps: accuracy (recovery), precision, detection limit, linearity, specificity, system adaptability.
Example 4
This example provides a method for measuring pramipexole dihydrochloride sustained release tablets (specification: 0.375mg, the theoretical pramipexole dihydrochloride content in the tablet is 0.375mg, which is 0.16% of the total tablet weight), the operation is different from that of example 1 only in the preparation method of the diluent in step (3): 7mL of trifluoroacetic acid and 3mL of hydrochloric acid (37%) were weighed out and placed in 1000mL of methanol, followed by mixing. All other conditions remained unchanged.
The methodology of the method is examined, and comprises the following steps: accuracy (recovery), precision, detection limit, linearity, specificity, system adaptability.
Comparative example 1
This example provides a method for measuring pramipexole dihydrochloride sustained release tablets (specification: 0.375mg, the theoretical pramipexole dihydrochloride content in the tablet is 0.375mg, which is 0.16% of the total tablet weight), the operation is different from that of example 1 only in the preparation method of the diluent in step (3): 10mL of hydrochloric acid (37%) was weighed into 1000mL of methanol and mixed well. All other conditions remained unchanged.
The methodology of the method is examined, and comprises the following steps: accuracy (recovery), precision, detection limit, linearity, specificity, system adaptability.
Example 5
This example provides a method for determining pramipexole dihydrochloride content in a pramipexole dihydrochloride sustained release tablet (specification: 0.375mg, the theoretical pramipexole dihydrochloride content in the tablet is 0.375mg, and the content is 0.16% of the total tablet weight), which is different from the operation of example 1 only in that the mobile phase a: no methanol was contained, 700mL of phosphate buffer was measured, mixed well and filtered through a 0.45 μm organic filter. All other conditions remained unchanged.
FIG. 5 is a chromatogram of the above sample.
Under the condition, the chromatographic peak of the pramipexole dihydrochloride has longer retention time and poor chromatographic peak shape, and is not suitable for measuring the content of the pramipexole dihydrochloride.
Example 6
This example provides a method for determining pramipexole dihydrochloride content in a pramipexole dihydrochloride sustained release tablet (specification: 0.375mg, the theoretical pramipexole dihydrochloride content in the tablet is 0.375mg, and the content is 0.16% of the total tablet weight), which is different from the operation of example 1 only in that the mobile phase a: 300mL of methanol and 700mL of phosphate buffer solution were weighed out, mixed well, and filtered through a 0.45 μm organic filter. All other conditions remained unchanged.
FIG. 6 is a chromatogram of the above sample.
Under the condition, the chromatographic peak of the pramipexole dihydrochloride has poor chromatographic peak shape, and is not suitable for measuring the content of the pramipexole dihydrochloride.
Example 7
This example provides a method for measuring pramipexole dihydrochloride sustained release tablets (specification: 0.375mg, the theoretical pramipexole dihydrochloride content in the tablet is 0.375mg, and the content of pramipexole dihydrochloride in the tablet is 0.16% of the total tablet weight), which is different from example 1 only in that the elution degree is isocratic: phase A: 80%, phase B: 20 percent. All other conditions remained unchanged.
The methodology of the method is examined, and comprises the following steps: accuracy (recovery), precision, detection limit, linearity, specificity, system adaptability.
Example 8
This example provides a method for measuring the pramipexole dihydrochloride content in a pramipexole dihydrochloride sustained release tablet (specification: 0.375mg, the theoretical pramipexole dihydrochloride content in the tablet is 0.375mg, and the theoretical pramipexole dihydrochloride content in the tablet is 0.16% of the total tablet weight), and the operation is different from that in example 1 only in that the elution degree is gradient elution as follows. All other conditions remained unchanged.
The methodology of the method is examined, and comprises the following steps: accuracy (recovery), precision, detection limit, linearity, specificity, system adaptability.
Test example 1
The recovery data for the above examples 1-4, 7-8 and comparative example 1 are shown in table 1: three parts (9 parts of samples) of the test solution with the concentration of 80%, 100% and 120% are prepared respectively, the content of the sample solution is measured respectively, and the measured value is compared with the theoretical value to calculate the recovery rate.
TABLE 1
Test example 2
Precision data for examples 1-4, 7-8 and comparative example 1 above are shown in table 2: 6 parts of each of the test solutions having a concentration of 100% were prepared, and tested by an analyst under the same conditions as much as possible, and the relative standard deviation (RSD%) of the contents of the 6 parts of the test solutions was calculated.
TABLE 2
| Group of | Relative standard deviation (RSD%) |
| Example 1 | 1.2 |
| Example 2 | 1.1 |
| Example 3 | 1.3 |
| Example 4 | 0.5 |
| Example 7 | 3.1 |
| Example 8 | 2.8 |
| Comparative example 1 | 6.7 |
Test example 3
The results of the linear evaluations of the above examples 1 to 4, 7 to 8 and comparative example 1 are shown in Table 3: 5 parts of test sample solutions with the concentrations of 50%, 75%, 100%, 125% and 150% are prepared respectively, the areas of main peaks are measured respectively, and the corresponding contents are calculated. Taking the content as an abscissa (X) and the peak area as an ordinate (Y), linear regression analysis is performed, and a relative coefficient (R) of a regression line is calculated.
TABLE 3
| Group of | Relative coefficient (R) |
| Example 1 | 1.000 |
| Example 2 | 1.000 |
| Example 3 | 1.000 |
| Practice ofExample 4 | 1.000 |
| Example 7 | 0.996 |
| Example 8 | 0.996 |
| Comparative example 1 | 0.997 |
Test example 4
The results of the evaluation of the suitability of the systems of the above examples 1 to 4, 7 to 8 and comparative example 1 are shown in Table 4: respectively preparing 6 test sample solutions with the concentration of 100% for analysis, and calculating the relative standard deviation of the peak area of the main peak, the relative standard deviation of the retention time of the main peak and the tailing factor of the main peak.
TABLE 4
Test example 5
The results of the specificity evaluation of the above examples 1 to 4, 7 to 8 and comparative example 1 were: the method has good specificity, and has no interference to the content determination of the pramipexole dihydrochloride.
The applicant states that the method for measuring the pramipexole dihydrochloride content in the pramipexole dihydrochloride sustained release tablets according to the present invention is illustrated by the above examples, but the present invention is not limited to the above examples, i.e., the present invention does not mean that the present invention must be implemented by the above examples. It should be understood by those skilled in the art that any modification of the present invention, equivalent substitutions of the raw materials of the product of the present invention, addition of auxiliary components, selection of specific modes, etc., are within the scope and disclosure of the present invention.
The preferred embodiments of the present invention have been described in detail, however, the present invention is not limited to the specific details of the above embodiments, and various simple modifications may be made to the technical solution of the present invention within the technical idea of the present invention, and these simple modifications are within the protective scope of the present invention.
It should be noted that the various technical features described in the above embodiments can be combined in any suitable manner without contradiction, and the invention is not described in any way for the possible combinations in order to avoid unnecessary repetition.
Claims (10)
1. A method for measuring the pramipexole dihydrochloride content in a pramipexole dihydrochloride sustained-release tablet is characterized by comprising the following steps:
mixing the sustained-release tablet to be detected with a diluent, performing ultrasonic treatment, detecting the solution by adopting a liquid chromatography, and calculating by using an external standard method to obtain the content of pramipexole dihydrochloride; the diluent is a methanol solution containing trifluoroacetic acid.
2. The method for determining pramipexole dihydrochloride sustained release tablets according to claim 1, wherein the concentration of trifluoroacetic acid in the diluent is 0.5-1.5%.
3. The method for determining pramipexole dihydrochloride content in pramipexole dihydrochloride sustained release tablets according to claim 1 or 2, wherein the diluent further comprises hydrochloric acid;
preferably, the mass ratio of the hydrochloric acid to the trifluoroacetic acid is 1 (2-10);
preferably, the sustained release tablet to be tested is completely disintegrated by ultrasonic wave.
4. The method for determining pramipexole dihydrochloride content in pramipexole dihydrochloride sustained-release tablets according to any one of claims 1 to 3, wherein the stationary phase in the liquid chromatography is octadecylsilane chemically bonded silica.
5. The method for determining pramipexole dihydrochloride content in pramipexole dihydrochloride sustained release tablets according to any one of claims 1 to 4, wherein the mobile phase in the liquid chromatography comprises an A phase and a B phase, the A phase is a mixed solution of methanol and a phosphate buffer solution, and the B phase is acetonitrile.
6. The method for determining pramipexole dihydrochloride sustained release tablets according to claim 5, wherein the phosphate buffer has a pH value of 2.5-3.5;
preferably, the volume ratio of the phosphate buffer solution to the methanol is (5-10): 1.
7. The method for determining pramipexole dihydrochloride content in pramipexole dihydrochloride sustained release tablets according to claim 5, wherein the preparation method of the phosphate buffer solution comprises the following steps:
mixing potassium dihydrogen phosphate, sodium octane sulfonate and water in a mass ratio of (1-2):1 (100-), (300), adjusting the pH value to 2.5-3.5 by using phosphoric acid or sodium hydroxide, and shaking up.
8. The method for determining pramipexole dihydrochloride content in pramipexole dihydrochloride sustained release tablets according to any one of claims 1 to 7, wherein the liquid chromatography adopts a gradient elution mode, and the gradient elution degree is as follows: 0min, 70-90% of phase A and 10-30% of phase B; 15min, 50-70% of phase A and 30-50% of phase B; 16min, 70-90% of phase A and 10-30% of phase B; 20min, 70-90% of phase A and 10-30% of phase B.
9. The method for determining the pramipexole dihydrochloride content in the pramipexole dihydrochloride sustained release tablets as claimed in any one of claims 1 to 8, wherein the detection wavelength is 262-266nm in the liquid chromatography; the column temperature is 35-45 ℃.
10. The method for determining pramipexole dihydrochloride content in pramipexole dihydrochloride sustained release tablets according to any one of claims 1 to 9, wherein the flow rate in the liquid chromatography is 1.0 to 2.0 mL/min; the injection volume is 5-25 μ L.
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| CN115128184A (en) * | 2022-06-20 | 2022-09-30 | 上海橡实化学有限公司 | Method for determining content of thiourea in pramipexole dihydrochloride raw material by using HPLC (high performance liquid chromatography) external standard method |
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