CN111487348B - Pramipexole dihydrochloride solution prepared by pramipexole dihydrochloride solid preparation and determination method thereof - Google Patents
Pramipexole dihydrochloride solution prepared by pramipexole dihydrochloride solid preparation and determination method thereof Download PDFInfo
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Abstract
The invention aims to provide a pramipexole dihydrochloride solution prepared by a pramipexole dihydrochloride solid preparation and a determination method thereof, and provides a method for preparing the pramipexole dihydrochloride solution by using pramipexole dihydrochloride sustained-release tablets, which has the advantages of short detection time consumption, high efficiency, readily available raw materials and low cost. When the pramipexole dihydrochloride solution prepared by the method is used for detecting pramipexole dihydrochloride in the pramipexole dihydrochloride sustained-release tablets, the method disclosed by the invention is found to accord with the guide principle of verification of the Chinese pharmacopoeia method in aspects of system applicability, specificity, precision, detection limit, quantification limit and the like, and the detection method is unexpectedly found to have higher accuracy compared with the existing method, and has great significance for manufacturers of pramipexole dihydrochloride preparations.
Description
Technical Field
The invention belongs to the technical field of pharmaceutical analysis, and particularly relates to a pramipexole dihydrochloride solution prepared from a pramipexole dihydrochloride solid preparation and a determination method thereof.
Background
Pramipexole was developed by Boehringer-Ingelheim, germany, and pramipexole dihydrochloride immediate-release tablets (pramipexoledihydrochloride immedate release tablets) were first marketed in 1997 in the united states; in 2007, pramipexole dihydrochloride (seofulo) was marketed in china. The curative effect and the safety of the pramipexole dihydrochloride tablets are consistently approved by doctors and patients after more than 20 years of clinical application.
Pramipexole is a non-ergot dopamine receptor agonist, acts on D2 and D3 receptors with high selectivity, and has obviously higher affinity for the D3 receptor than the D2 receptor. By selectively exciting the striatal postsynaptic membrane D2, D3 receptors, motor symptoms in PD patients are ameliorated; pramipexole had no effect on dopamine D1 and D5 receptors, alpha-adrenergic receptors, beta-adrenergic receptors, acetylcholine receptors, and 5-hydroxytryptamine receptors. Pramipexole is a non-ergot dopamine agonist with higher relative in vitro specificity and global intrinsic activity in the D2 dopamine receptor subfamily and higher affinity for the D2 or D4 receptor subtype than for D3. The product can be used for treating characteristics and symptoms of adult idiopathic Parkinson disease, i.e. in the whole disease process including later stage, when the curative effect of levodopa gradually weakens or changes and fluctuates, the product can be used alone (without levodopa) or combined with levodopa.
Pramipexole is BCS I type, pramipexole dihydrochloride preparation, and the slow release effect of pramipexole dihydrochloride is realized through prescription auxiliary materials and a process. The pramipexole dihydrochloride preparation contains two auxiliary materials including HPMC and carbomer, so that tablets are difficult to disintegrate and the main component is difficult to extract. In the national institute of food and drug administration imported drug registration standard, powdered pramipexole dihydrochloride sustained release tablets are added with a methanol-acetonitrile-phosphoric acid solvent, after shaking, a phosphoric acid buffer solution and an enzyme solution are added, after shaking, the phosphoric acid buffer solution is used for dilution, and then the enzyme solution is filtered by a filter membrane.
In the european union pharmacopoeia, a powdery pramipexole dihydrochloride sustained release tablet is mixed and shaken with a solution A, the solution A is formed by mixing methanol and a mobile phase A, the mobile phase A is a mixed solution of potassium dihydrogen phosphate and sodium octane sulfonate which are regulated to pH3.0 by phosphoric acid, and the method has the defects that the pramipexole dihydrochloride sustained release tablet cannot be directly dissolved in the solution A, the pramipexole dihydrochloride sustained release tablet is necessarily ground into powder in advance, and the detection result accuracy is not high.
Disclosure of Invention
In order to solve the problems, the invention provides a method for preparing a pramipexole dihydrochloride solution by using a pramipexole dihydrochloride solid preparation, which has the advantages of short detection time consumption, high efficiency, readily available raw materials and low cost. When the pramipexole dihydrochloride solution prepared by the method is used for detecting pramipexole dihydrochloride in the pramipexole dihydrochloride solid preparation, the method disclosed by the invention is found to accord with the guide principle of verification of the Chinese pharmacopoeia method in aspects of system applicability, specificity, precision, detection limit, quantification limit and the like, and the method is unexpectedly found to have higher accuracy compared with the existing method, and has great significance for manufacturers of pramipexole dihydrochloride preparations.
The invention provides a pramipexole dihydrochloride solution prepared by a pramipexole dihydrochloride solid preparation, which comprises the pramipexole dihydrochloride solid preparation, isopropanol, dimethyl sulfoxide, acetonitrile and a buffer solution with the pH value of 3.0, and the pramipexole dihydrochloride solid preparation does not need to be ground.
The invention provides a preparation method of a pramipexole dihydrochloride solution, which comprises the following steps: adding the pramipexole dihydrochloride solid preparation into an isopropanol solvent, standing, adding a dimethyl sulfoxide solvent after standing, adding a mixed solution of acetonitrile and a buffer solution with the pH value of 3.0 after magnetic stirring or magnetic stirring and ultrasound, uniformly mixing, centrifuging, and filtering to obtain a filtrate, namely the pramipexole dihydrochloride solution.
According to the preparation method of the pramipexole dihydrochloride solution, isopropanol is added into the solid pramipexole dihydrochloride preparation and then the solid pramipexole dihydrochloride preparation is kept stand for 3-7 min, and the time of magnetic stirring or magnetic stirring plus ultrasound after dimethyl sulfoxide is added is 15-25 min.
The preparation method of the pramipexole dihydrochloride solution comprises the following specific operations of adding the mixed solution, uniformly mixing, and centrifuging: the mixture was added, sonicated, occasionally shaken under sonication, and recentrifuged. The ultrasonic time in the step is 30-100 min, preferably 50-70 min; the centrifugation time in the step is 10-30 min, preferably 15-25 min, and the centrifugation rotating speed is 8500-10000 rpm; after the centrifugation, the mixture is filtered by a filter membrane of 0.45 mu m.
According to the preparation method of the pramipexole dihydrochloride solution, the pramipexole dihydrochloride solid preparation has the following mass: volume of isopropyl alcohol: volume of dimethyl sulfoxide 1.3mg: (10-70 mL), wherein the mass of the pramipexole dihydrochloride preparation is calculated by the mass of the pramipexole dihydrochloride serving as the raw material of the tablet.
According to the preparation method of the pramipexole dihydrochloride solution, the pramipexole dihydrochloride solid preparation comprises pramipexole dihydrochloride tablets, sustained-release tablets or enteric-coated tablets.
According to the preparation method of the pramipexole dihydrochloride solution, the pramipexole dihydrochloride solution prepared by the method is used for quality control of API in the pramipexole dihydrochloride solid preparation.
The invention also provides a method for detecting pramipexole dihydrochloride in the pramipexole dihydrochloride sustained-release solid preparation, which comprises the following steps: (1) Preparing solutions, namely preparing a blank solution, a blank auxiliary material solution, a pramipexole hydrochloride reference substance solution and a pramipexole hydrochloride sample solution respectively; the blank solution comprises isopropanol, dimethyl sulfoxide and a diluted solution; the blank auxiliary material solution is prepared from blank auxiliary materials, isopropanol, dimethyl sulfoxide and diluent; the blank auxiliary materials are all substances except the pramipexole dihydrochloride in the pramipexole dihydrochloride solid preparation; the pramipexole dihydrochloride reference solution is prepared from pramipexole dihydrochloride monohydrate, isopropanol, dimethyl sulfoxide and a diluent; the pramipexole dihydrochloride sample solution is prepared by adopting the method for preparing the pramipexole dihydrochloride solution by adopting the pramipexole dihydrochloride solid preparation; (2) The prepared solution was measured by HPLC method.
The invention discloses a method for detecting pramipexole dihydrochloride in a pramipexole dihydrochloride solid preparation, which comprises the following steps of: respectively injecting the blank solution, the pramipexole dihydrochloride reference solution and the pramipexole dihydrochloride sample solution into a liquid chromatograph, and recording a chromatogram, wherein the chromatogram conditions are as follows: and (3) chromatographic column: inertsil ODS-3V (150X 4.6 mm), 5 μm; the flow rate is 1.5 plus or minus 0.2mL/min; column temperature: 40 +/-3 ℃; temperature of the sample: 25 ℃; sample injection volume: 100 mul; operating time: 20min; detection wavelength: 264nm; the mobile phase is an A-B system and gradient elution is carried out.
According to the detection method of pramipexole dihydrochloride in the pramipexole dihydrochloride solid preparation, the mobile phase A is a buffer solution with the pH value of 3.0; the mobile phase B is the volume of the mobile phase A: the volume of the acetonitrile is 50; the diluent is acetonitrile in volume: mobile phase a volume was 20:80; the mobile phase gradient process is as follows:
| time (min) | Mobile phase A (%) | Mobile phase B (%) |
| 0 | 60 | 40 |
| 15 | 20 | 80 |
| 15.1 | 60 | 40 |
| 20 | 60 | 40 |
According to the detection method of pramipexole dihydrochloride in the pramipexole dihydrochloride solid preparation, the buffer solution consists of potassium dihydrogen phosphate, sodium octane sulfonate and phosphoric acid.
Advantageous effects
The beneficial effects of the invention are mainly embodied in the following points:
1. in the prior art, when the content of pramipexole dihydrochloride in pramipexole dihydrochloride sustained-release tablets is detected and a pramipexole dihydrochloride sample solution is prepared, the pramipexole dihydrochloride sustained-release tablets need to be ground into powder and then dissolved, so that the content of pramipexole dihydrochloride in the pramipexole dihydrochloride sustained-release tablets is detected; the invention discloses a method for directly preparing a pramipexole dihydrochloride solution by using a pramipexole dihydrochloride solid preparation, which does not need to grind the pramipexole dihydrochloride solid preparation into powder, and the prepared pramipexole dihydrochloride solution can be used for detecting the content of pramipexole dihydrochloride in the pramipexole dihydrochloride solid preparation.
2. When the pramipexole dihydrochloride solution prepared by the method is used for detecting pramipexole dihydrochloride in the pramipexole dihydrochloride sustained-release tablets, the method disclosed by the invention is found to accord with the guiding principle of verification of the Chinese pharmacopoeia method in the aspects of system applicability, specificity, precision, detection limit, quantification limit and the like, and the detection method disclosed by the invention is unexpectedly found to have obviously higher accuracy compared with the existing method in the prior art. Under the condition that a detection solution, a reference substance solution, a detection instrument and an operator are the same, a detection method recorded in European Union pharmacopoeia and the method disclosed by the invention are respectively adopted for detection, the detection result of the European Union pharmacopoeia is 94.2%, the detection result of the method disclosed by the invention is 101.1%, the difference between the detection results is 7%, in the field of human medicine, according to the ICH guiding principle, if the difference between the detection results of two times is 2% -3%, the error can be considered, and if the difference between the detection results of two times is 5% or more, the obvious difference can be considered, and the methods are obviously different. In the invention, because other conditions are the same, only the detection methods are different, the difference between the results of the two methods is 7%, and the result of the method is 101.1%, obviously, the result of the method is closer to the true value, the accuracy of the method is higher, the accuracy of the detection method is crucial to the determination of whether the product of a preparation manufacturer is qualified, and the detection method has great significance to the manufacturers of the pramipexole dihydrochloride preparations.
3. The detection method of the invention comprises the following steps of: results of system applicability: the theoretical plate number is not less than 2000, the tailing factor is not more than 2.0, the blank solution has no interference at the retention time of the pramipexole hydrochloride, the blank auxiliary material solution has no interference at the retention time of the pramipexole hydrochloride, and all impurity peaks in the sample solution are well separated from the chromatographic peak of the pramipexole hydrochloride; in the durability experiment, when the flow rate is changed to +/-0.2 mL/minute, the system applicability parameters are not changed, and the system applicability parameters of the durability samples at 45 ℃ and 35 ℃ are basically not changed; in the recovery rate test, the recovery filter results settled by the reference solution (2.8 ppm) are 100.5 percent (30 percent of sample preparation), 100.8 percent (30 percent of sample preparation), 101.2 percent (30 percent of sample preparation), and the recovery filter results settled by the reference solution (10 ppm) are 99.3 percent (30 percent of sample preparation), 99.0 percent (30 percent of sample preparation) and 100.2 percent (30 percent of sample preparation); the content test result in the precision test is 97.5%, and the RSD% of 6 parts of samples is 1.79%; in the solution stability experiment, the change values of 19h at room temperature are 1.01 percent and 1.00 percent, the change values of 48h at room temperature are 0.99 percent and 1.00 percent, the change values of 19h in a refrigerator are 0.4 percent and 0.1 percent, and the change values of 48h in the refrigerator are-1.1 percent and-1.8 percent; in the filter membrane applicability test, the similarity factor of the filtered sample is 99.9%, the similarity factor of the non-filtered sample is 100.07%, and the difference between the two samples is 0.8.
Detailed Description
The invention will be further explained and illustrated by the following specific examples, which are not intended to limit the scope of the invention in any way.
Example 1
Preparation of pramipexole dihydrochloride solution according to the invention (sample specification: API:0.26 mg): and (3) taking 5 pramipexole sustained-release tablets, precisely weighing, placing in a 500ml measuring flask, adding 25ml isopropanol, and standing for 5min. Adding 25ml of dimethyl sulfoxide, and magnetically stirring for 20min at the rotating speed of 1000rpm; adding 350ml of diluent, performing ultrasonic treatment for 60min, occasionally shaking in the ultrasonic treatment, taking out the stirrer, and performing constant volume treatment to scale with the diluent; centrifuge at 9000rpm for 20min. Filtering the solution by using a 0.45 mu m filter membrane, and then discarding 3ml of primary filtrate to obtain the pramipexole dihydrochloride solution.
Comparative example 1 dissolution of sample solutions according to the invention in different solvent systems
According to the invention, a large amount of experimental researches show that the pramipexole dihydrochloride sustained-release tablets can be directly prepared into a pramipexole dihydrochloride solution for HPLC detection by using isopropanol and DMSO, but when a solvent system is changed, namely the isopropanol and DMSO system in example 1 is replaced by the following solvent system, an ideal pramipexole dihydrochloride solution cannot be obtained. Referring to the method of preparing the solution of example 1, the experimental results are as follows:
TABLE 1 preparation of pramipexole dihydrochloride sustained release tablets in different solvent systems
When the solvent system was not changed, but the solvent content was changed or the order of addition of the solvents was changed, as shown in the following table:
TABLE 2 preparation of pramipexole dihydrochloride sustained release tablets with different solvent addition sequences and solvent amounts
And (4) conclusion: the preparation of the pramipexole dihydrochloride sustained release tablet is to adopt the method of firstly adding isopropanol and standing, then adding DMSO and stirring, wherein the adding volume of the isopropanol and the DMSO is defined by the invention, if the amount of the isopropanol and the DMSO is too small, the sustained release tablet is not completely disintegrated, the pramipexole dihydrochloride cannot be completely dissolved in a solvent, if the amount of the isopropanol and the DMSO is too large, the service life of instruments and consumables is influenced, and meanwhile, the peak shape of a chromatographic peak is influenced, and the detection sensitivity and accuracy are influenced; if isopropanol and DMSO are added simultaneously, the sustained release tablet does not swell and disintegrate; if the order of addition is changed, the sustained-release tablet does not swell and disintegrate.
Example 2
1. Experimental materials and instrumentation conditions
Experimental materials: acetonitrile, manufacturer: rankem; phosphoric acid, manufacturer: merck; monopotassium phosphate, manufacturer: merck; anhydrous sodium 1-octanesulfonate, manufacturer: rankem; dimethyl sulfoxide, manufacturer: rankem; isopropanol, manufacturer: merck; ultrapure water, manufacturer: zhuhairun pharmaceutical products, inc.; pramipexole dihydrochloride sustained release tablets, manufacturer: zuhairun pharmaceutical products, inc, specification: 0.26mg, 0.58mg, 1.05mg.
The instrument comprises: high performance liquid chromatograph: agilent 1260; an ultrasonic instrument: a pH meter: lab India-PICO +; a semi-microbalance: radwag-XA 82/220/2X; ultrasonic instrument: PCI analytics; a constant temperature oscillator: glass co; a centrifuge: eltek; electronic analytical balance XSE205DU, GR-200; a chromatographic column: inertsil ODS-3V (150X 4.6 mm), 5 μm.
The detection method comprises the following steps: respectively injecting the blank solution, the pramipexole dihydrochloride reference solution (n = 5) and the pramipexole dihydrochloride sample solution into a liquid chromatograph in sequence, and recording chromatograms, wherein the chromatographic conditions are as follows: a chromatographic column: inertsil ODS-3V (150X 4.6 mm), 5 μm; the flow rate is 1.5mL/min plus or minus 0.2mL/min; column temperature: 40 +/-5 ℃; temperature of the sample: 25 ℃; sample introduction volume: 100 mul; operating time: 20min; detection wavelength: 264nm; the mobile phase is an A-B system, the mobile phase A is a buffer solution with the pH value of 3.0 and contains potassium dihydrogen phosphate, sodium octane sulfonate and phosphoric acid, and the mobile phase B is a mobile phase A: acetonitrile (50, volume ratio), gradient elution was performed, with the following gradient:
| time (min) | Mobile phase A (%) | Mobile phase B (%) |
| 0 | 60 | 40 |
| 15 | 20 | 80 |
| 15.1 | 60 | 40 |
| 20 | 60 | 40 |
2. Experimental procedure
1. Preparing a 10% phosphoric acid solution: 2ml of phosphoric acid was diluted to 20ml with water.
2. Mobile phase a (ph 3.0 buffer) was prepared: 9.1g of sodium dihydrogen phosphate and 5.0g of sodium octane sulfonate were weighed and dissolved in 1L of water by ultrasound, and then the pH was adjusted to 3.0 with 10% phosphoric acid solution, and the solution was filtered through a 0.45 μm filter membrane and degassed by ultrasound to obtain a mobile phase A (pH 3.0 buffer).
3. Preparing a mobile phase B: and measuring the mobile phase A and acetonitrile, mixing, and performing ultrasonic degassing to obtain a mobile phase B.
4. Preparing a diluent: weighing acetonitrile and the mobile phase A, and mixing and shaking uniformly to obtain the diluent.
5. Preparing a blank solution: transferring 1.0ml of isopropanol and 1.0ml of dimethyl sulfoxide into a 20ml volumetric flask, diluting to a scale with a diluent, fully and uniformly mixing, filtering with a 0.45 mu m nylon filter membrane, discarding 3ml of primary filtrate, and collecting continuous filtrate to obtain a blank solution.
6. Preparing a pramipexole dihydrochloride reference substance stock solution: accurately weighing about 25mg of pramipexole dihydrochloride monohydrate, placing the pramipexole dihydrochloride monohydrate into a 250ml volumetric flask, adding 170ml of diluent for ultrasonic dissolution, diluting the solution with the diluent to a constant volume to a scale, and filtering the solution through a 0.45 mu m filter membrane to obtain a pramipexole dihydrochloride reference substance stock solution. (about 70 ppm)
7. Control solution preparation 0.26mg gauge: precisely transferring 4.0ml of pramipexole dihydrochloride reference substance stock solution into a 100ml volumetric flask, adding 5ml of isopropanol and 5ml of dimethyl sulfoxide, fixing the volume to the scale by using a diluent, and filtering by using a 0.45-micrometer filter membrane to obtain the reference substance solution with the specification of 0.26 mg. (about 2.8 ppm)
8. Preparation of pramipexole dihydrochloride sample solution (sample specification: 0.26 mg): and (3) taking 5 pramipexole sustained-release tablets, precisely weighing, placing in a 500ml measuring flask, adding 25ml isopropanol, and standing for 5min. Adding 25ml of dimethyl sulfoxide, and magnetically stirring for 20min at the rotating speed of 1000rpm; adding 350ml of diluent, performing ultrasonic treatment for 60min, occasionally shaking in the ultrasonic treatment, taking out the stirrer, and performing constant volume treatment to scale with the diluent; centrifuge at 9000rpm for 20min. After filtration through a 0.45 μm filter membrane, 3ml of the initial filtrate was discarded, and the subsequent filtrate was analyzed.
9. Preparing a blank auxiliary material solution: precisely weighing 5 times of the prescription amount of blank auxiliary materials in a 500mL measuring flask, adding 25mL of isopropanol, standing for 5min, adding 25mL of isopropanol, adding 25mL of dimethyl sulfoxide, magnetically stirring for 20min, rotating at 1000rpm, adding 350mL of diluent, and performing ultrasonic treatment for 1h while shaking occasionally; adding diluent to constant volume, and fully mixing; centrifuging the appropriate amount of solution at 9000rpm for 10min, filtering with 0.45 μm filter membrane, discarding 3ml of primary filtrate, and collecting the subsequent filtrate for analysis. (the blank auxiliary materials are the rest substances except the pramipexole dihydrochloride in the pramipexole dihydrochloride sustained-release tablets).
Sample introduction procedure: and after the system is stabilized, performing recalibration on the reference substance solution before the end of the sequence and at the interval of about 8 hours by using 1 needle of the blank solution, 5 needles of the first reference substance solution, 1 needle of the second reference substance solution and 1 needle of the pramipexole dihydrochloride sample solution respectively. And recording the chromatogram, and calculating the peak area by using an external standard method. The first measurement result is 99.48%, the second measurement result is 102.65%, and the average content is taken, so that the content of pramipexole dihydrochloride in the sample is 101.1%.
Example 3 specificity test of the detection method of the invention
The specificity is to investigate the identification and selectivity of the detected components, and blank solution and blank auxiliary materials are required to have no interference on the detection of the pramipexole dihydrochloride; in the adaptive solution of the system, all impurity peaks are well separated from the pramipexole dihydrochloride chromatographic peak.
Interference evaluation of blank solutions and blank adjuvant solutions: the blank solution (diluent), the control solution and the blank adjuvant solution were analyzed separately according to the content measurement analysis method.
And (4) conclusion: the theoretical plate number is not less than 2000, the tailing factor is not more than 2.0, the blank solution has no interference at the retention time of the pramipexole, the blank auxiliary material solution has no interference at the retention time of the pramipexole dihydrochloride, and all impurity peaks in the sample solution are well separated from the chromatographic peak of the pramipexole dihydrochloride.
Comparative example 2
The results were measured according to the methods of the European Union pharmacopoeia
The diluent, mobile phase A and mobile phase B were the same as in example 3.
The blank solution is the dilution.
Control stock solution: measuring 25mg of pramipexole dihydrochloride monohydrate reference substance, placing the reference substance in a 250ml volumetric flask, adding 170ml of diluent, performing ultrasonic dissolution, diluting the reference substance to a scale with the diluent, shaking up, and filtering the solution through a 0.45 mu m filter membrane to obtain pramipexole dihydrochloride reference substance stock solution (preparing two parts by the same method);
control solution: precisely transferring 4ml of the reference substance stock solution, placing the reference substance stock solution into a 100ml volumetric flask, and diluting the reference substance stock solution to a scale by using a diluent; filtering the solution with a filter membrane, and taking the subsequent filtrate as a reference substance (preparing two parts by the same method);
preparation of pramipexole dihydrochloride sample solution: weighing powder containing about 1.3mg of pramipexole, placing the powder into a 500ml measuring flask, adding a proper amount of diluent, and ultrasonically shaking the powder uniformly to dilute the powder to 500ml; the solution was filtered through a filter membrane and the subsequent filtrates were collected (two portions prepared in the same manner).
Sample introduction procedure: after the system is stabilized, 1 needle of blank solution, 5 needles of the first part of comparison product solution, 1 needle of the second part of comparison product solution and 1 needle of pramipexole dihydrochloride sample solution are respectively subjected to recalibration before the sequence is finished and at intervals of about 8 hours. The first measurement result is 95.21%, the second measurement result is 93.1%, and the average content is taken, so that the content of pramipexole dihydrochloride in the sample is 94.16%.
Claims (9)
1. The method for preparing the pramipexole dihydrochloride solution by using the pramipexole dihydrochloride solid preparation is characterized in that the pramipexole dihydrochloride solution comprises the pramipexole dihydrochloride solid preparation, isopropanol, dimethyl sulfoxide, acetonitrile and a buffer solution with the pH value of 3.0, the pramipexole dihydrochloride solid preparation does not need to be ground, and the method for preparing the pramipexole dihydrochloride solution by using the pramipexole dihydrochloride solid preparation comprises the following steps: adding the pramipexole dihydrochloride solid preparation into an isopropanol solvent, standing, adding a dimethyl sulfoxide solvent after standing, adding a mixed solution of acetonitrile and a buffer solution with the pH value of 3.0 after magnetic stirring or magnetic stirring and ultrasound, uniformly mixing, centrifuging, and filtering to obtain a filtrate, namely the pramipexole dihydrochloride solution.
2. The method according to claim 1, wherein the pramipexole dihydrochloride solid preparation is allowed to stand for 3 to 7min after being added with isopropanol, and then is subjected to magnetic stirring by adding dimethyl sulfoxide or magnetic stirring and ultrasound for 15 to 25min after being allowed to stand.
3. The method according to claim 2, wherein the specific operations of adding the mixed solution, uniformly mixing and centrifuging are as follows: adding the mixed solution, performing ultrasonic treatment, occasionally shaking in the ultrasonic treatment, and centrifuging; the ultrasonic time in the step is 50-70 min; the centrifugation time in the step is 15-25 min, and the centrifugation rotating speed is 8500-10000 rpm; after the centrifugation, the mixture is filtered by a filter membrane of 0.45 mu m.
4. The method according to any one of claims 2 to 3, wherein the pramipexole dihydrochloride solid preparation has the following mass: volume of isopropyl alcohol: volume of dimethyl sulfoxide 1.3mg: 10-70mL, wherein the mass of the pramipexole dihydrochloride solid preparation is calculated by the mass of the pramipexole dihydrochloride serving as the raw material of the tablet.
5. The method of claim 4, wherein the solid pramipexole dihydrochloride formulation comprises pramipexole dihydrochloride tablets.
6. The method of claim 5, wherein the pramipexole dihydrochloride solution prepared by the method is used for quality control of API in pramipexole dihydrochloride solid preparation.
7. A method for detecting pramipexole dihydrochloride in a pramipexole dihydrochloride sustained-release solid preparation is characterized by comprising the following steps: (1) Preparing solutions, namely respectively preparing a blank solution, a blank auxiliary material solution, a pramipexole hydrochloride reference substance solution and a pramipexole hydrochloride sample solution; the blank solution comprises isopropanol, dimethyl sulfoxide and diluent; the blank auxiliary material solution is prepared from blank auxiliary materials, isopropanol, dimethyl sulfoxide and diluent; the blank auxiliary materials are all substances except the pramipexole dihydrochloride in the pramipexole dihydrochloride solid preparation; the pramipexole dihydrochloride reference solution is prepared from pramipexole dihydrochloride monohydrate, isopropanol, dimethyl sulfoxide and a diluent; the diluent is acetonitrile volume: mobile phase a volume 20:80, the mobile phase A is a buffer solution with pH 3.0; the pramipexole dihydrochloride sample solution is prepared by the method of any one of claims 1 to 6; (2) The prepared solution was measured by HPLC measurement method.
8. The detection method according to claim 7, wherein the HPLC determination method is: respectively injecting the blank solution, the pramipexole dihydrochloride reference solution and the pramipexole dihydrochloride sample solution into a liquid chromatograph, and recording a chromatogram, wherein the chromatogram conditions are as follows: and (3) chromatographic column: inertsil ODS-3V, 150X 4.6mm,5 μm; the flow rate is 1.5 plus or minus 0.2mL/min; column temperature: 40 +/-3 ℃; temperature of the sample: 25 ℃; sample injection volume: 100 mul; operating time: 20min; detection wavelength: 264nm; the mobile phase is an A-B system and gradient elution is carried out.
9. The detection method according to claim 8, wherein the mobile phase B is a mobile phase A volume: the volume of acetonitrile is 50:50; the mobile phase gradient process is as follows:
The buffer solution consists of potassium dihydrogen phosphate, sodium octane sulfonate and phosphoric acid.
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