CN111487348A - 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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- CN111487348A CN111487348A CN202010362116.5A CN202010362116A CN111487348A CN 111487348 A CN111487348 A CN 111487348A CN 202010362116 A CN202010362116 A CN 202010362116A CN 111487348 A CN111487348 A CN 111487348A
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- G—PHYSICS
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
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- G01N30/8675—Evaluation, i.e. decoding of the signal into analytical information
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- G—PHYSICS
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- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/04—Preparation or injection of sample to be analysed
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- G01N2030/065—Preparation using different phases to separate parts of sample
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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 agonist, acts on D2 and D3 receptors with high selectivity, has obviously higher affinity to D3 receptor than D2 receptor, improves the motor symptoms of PD patients by selectively exciting the striatal postsynaptic membrane D2 and D3 receptors, has no effect on dopamine D1 and D5 receptors, α -adrenergic receptors, β -adrenergic receptors, acetylcholine receptors and 5-hydroxytryptamine receptors, is a non-ergot dopamine agonist, has higher relative in vitro specificity and full intrinsic activity in the D2 dopamine receptor subfamily, and has higher affinity to the D2 or D4 receptor subtypes compared with D3.
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 centrifuged again. The ultrasonic time in the step is 30-100 min, preferably 50-70 min; in the step, the centrifugation time 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.
The preparation method of the pramipexole dihydrochloride solution comprises the following steps of taking the mass of a pramipexole dihydrochloride solid preparation, namely the mass of isopropanol, the volume of dimethyl sulfoxide, and the mass of the pramipexole dihydrochloride solid preparation, namely (10-70 m L) and (10-70 m L), and taking the mass of the pramipexole dihydrochloride solid preparation in terms of the mass of a raw material, namely pramipexole dihydrochloride, in a 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 of (1) preparing a solution, respectively preparing a blank solution, a blank auxiliary material solution, a pramipexole dihydrochloride reference solution and a pramipexole dihydrochloride sample solution, wherein the blank solution comprises isopropanol, dimethyl sulfoxide and a diluent, the blank auxiliary material solution is prepared from blank auxiliary materials, isopropanol, dimethyl sulfoxide and the diluent, the blank auxiliary materials are all substances except pramipexole dihydrochloride in the pramipexole dihydrochloride solid preparation, the pramipexole dihydrochloride reference solution is prepared from pramipexole dihydrochloride monohydrate, isopropanol, dimethyl sulfoxide and the diluent, the pramipexole dihydrochloride sample solution is prepared by adopting the method for preparing the pramipexole dihydrochloride solution prepared from the pramipexole dihydrochloride solid preparation, and (2) the prepared solution is measured by an HP L C measuring method.
The invention relates to a method for detecting pramipexole dihydrochloride in a pramipexole dihydrochloride solid preparation, which comprises the steps of injecting a blank solution, a pramipexole dihydrochloride reference solution and a pramipexole dihydrochloride sample solution into a liquid chromatograph, and recording a chromatogram, wherein the chromatogram comprises the following chromatographic conditions of Inertsil ODS-3V (150 ×.6mm) and 5 mu m, the flow rate of 1.5 +/-0.2 m L/min, the column temperature of 40 +/-3 ℃, the sample temperature of 25 ℃, the sample injection volume of 100 mu l, the running time of 20min, the detection wavelength of 264nm and the mobile phase of an A-B system for gradient elution.
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: 50; the diluent is acetonitrile volume: mobile phase a volume was 20: 80; the mobile phase gradient process is as follows:
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 sample solution is detected, and the pramipexole dihydrochloride is a high-activity component which has a large influence on healthy people, and other chemical substances and can be toxic and harmful, and the analysis and grinding is usually manual grinding and can damage the health of operators; the invention discloses a method for directly preparing pramipexole dihydrochloride solution by using 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 aspects of system applicability, specificity, precision, detection limit, quantification limit and the like, and the detection method disclosed by the invention is surprisingly found to have 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 the 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%, and the difference between the detection results of the two is 7%. 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 provided by the invention has the following data verification results that the system applicability is that the theoretical plate number is not less than 2000, the tailing factor is not more than 2.0, the blank solution is free of interference at the pramipexole retention time, the blank auxiliary material solution is free of interference at the pramipexole hydrochloride retention time, all impurity peaks in the sample solution are well separated from the pramipexole hydrochloride chromatographic peak, the system applicability parameters are not changed when the flow rate is +/-0.2 m L/minute in the durability experiment, the system applicability parameters of the durability samples at 45 ℃ and 35 ℃ are basically unchanged, the recovery filtration results settled by the reference solution (2.8 ppm) in the durability experiment are 100.5 percent (sample preparation 30%), 100.8 percent (sample preparation 30%), 101.2 percent (sample preparation 30%), the recovery filtration results settled by the reference solution (10 ppm) are 99.3 percent (sample preparation 30 percent), 99.0 percent (sample preparation 30 percent), 100.2 percent (sample preparation 30 percent), 30 percent (sample preparation result in the test experiment, the content test result is 97.5 percent, the sample stability test result is 99 percent, the sample stability of the sample is placed in a refrigerator, the filter membrane is placed in the refrigerator.
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 5 min. Adding 25ml of dimethyl sulfoxide, and magnetically stirring for 20min at the rotating speed of 1000 rpm; adding 350ml of diluent, performing ultrasonic treatment for 60min, occasionally shaking in the ultrasonic treatment, taking out the stirrer, and fixing the volume to the scale by using the diluent; centrifuge at 9000rpm for 20 min. 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 a large amount of experimental researches, the pramipexole dihydrochloride sustained-release tablets can be directly prepared into a pramipexole dihydrochloride solution for HP L C detection by utilizing 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, and the experimental results are as follows according to the preparation method of the solution in example 1:
and (4) conclusion: the preparation of the pramipexole dihydrochloride sustained-release tablets should adopt the method that isopropanol is added firstly and then DMSO is added for stirring, the adding volume of the isopropanol and the DMSO is in accordance with the limitation of the invention, if the amount of the isopropanol and the DMSO is too small, the sustained-release tablets are 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 simultaneously 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
Experimental materials and instrument conditions
Experimental materials: acetonitrile, manufacturer: rankem; phosphoric acid, manufacturer: merck; potassium dihydrogen 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, 1.05 mg.
The instrument comprises a high performance liquid chromatograph Agilent 1260, an ultrasonic instrument L ab India-PICO +, a semi-microbalance Radwag-XA 82/220/2X, an ultrasonic instrument PCI analytical aids, a constant temperature oscillator Glass co, a centrifuge Eltek, an electronic analytical balance XSE205DU and GR-200, and a chromatographic column Inertsil ODS-3V (150 × 4.6.6 mm) with the size of 5 mu m.
The detection method comprises the steps of respectively injecting a blank solution, a pramipexole hydrochloride reference solution (n = 5) and a pramipexole hydrochloride sample solution into a liquid chromatograph in sequence, and recording a chromatogram, wherein the chromatographic conditions comprise a chromatographic column with Inertsil ODS-3V (150 × 4.6.6 mm) of 5 microns, a flow rate of 1.5m L/min +/-0.2 m L/min, a column temperature of 40 +/-5 ℃, a sample temperature of 25 ℃, a sample injection volume of 100 microns, a running time of 20min, a detection wavelength of 264nm, a mobile phase A-B system, a mobile phase A buffer solution with a pH value of 3.0 and containing potassium dihydrogen phosphate, sodium octane sulfonate and phosphoric acid, and the mobile phase B with a mobile phase A: acetonitrile (50: 50, volume ratio), and carrying out gradient elution, and the gradient is shown in Table 2.
Second, the experimental procedure
1. Preparing a 10% phosphoric acid solution: 2ml of phosphoric acid was diluted to 20ml with water.
2. And (3) preparing a mobile phase A (pH3.0 buffer solution), namely weighing 9.1g of sodium dihydrogen phosphate and 5.0g of sodium octane sulfonate in 1L water, ultrasonically dissolving, then adjusting the pH to 3.0 by using a 10% phosphoric acid solution, filtering by using a 0.45 mu m filter membrane, and ultrasonically degassing to obtain the mobile phase A (pH3.0 buffer solution).
3. Preparing a mobile phase B: and measuring the mobile phase A and acetonitrile, mixing, and then carrying out ultrasonic degassing to obtain the 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 the solution to a scale with a diluent, fully and uniformly mixing the solution, filtering the solution with a 0.45 mu m nylon filter membrane, discarding 3ml of primary filtrate, and collecting secondary 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 a scale by using a diluent, and filtering by using a 0.45 mu m filter membrane to obtain a 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 5 min. Adding 25ml of dimethyl sulfoxide, and magnetically stirring for 20min at the rotating speed of 1000 rpm; adding 350ml of diluent, performing ultrasonic treatment for 60min, occasionally shaking in the ultrasonic treatment, taking out the stirrer, and fixing the volume to the scale by using the diluent; centrifuge at 9000rpm for 20 min. 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, namely precisely weighing 5 times of the prescription amount of the blank auxiliary material in a 500m L measuring flask, adding 25ml of isopropanol, standing for 5min, adding 25ml of isopropanol, adding 25ml of dimethyl sulfoxide, magnetically stirring for 20min at the rotating speed of 1000rpm, adding 350ml of diluent, performing ultrasonic treatment for 1h, shaking from time to time, adding the diluent to the solution to a constant volume, fully mixing, taking a proper amount of solution, centrifuging for 10min at 9000rpm, filtering through a 0.45 mu m filter membrane, removing 3ml of primary filtrate, and taking a subsequent filtrate for analysis (the blank auxiliary material is the rest of the pramipexole dihydrochloride sustained-release tablets except pramipexole dihydrochloride).
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, and 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 a pramipexole dihydrochloride monohydrate reference substance, placing the reference substance in a 250ml volumetric flask, adding 170ml of diluent, ultrasonically dissolving, diluting to a scale with the diluent, shaking up, and filtering with a 0.45 mu m filter membrane to obtain a pramipexole dihydrochloride reference substance stock solution (two parts are prepared 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 up to dilute the powder to 500 ml; the solution was filtered through a filter membrane and the subsequent filtrates were collected (two portions prepared in the same manner).
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. The first measurement was 95.21%, the second measurement was 93.1%, and the pramipexole dihydrochloride content in this sample was 94.16% by taking the average content.
Claims (10)
1. The pramipexole dihydrochloride solution prepared from the pramipexole dihydrochloride solid preparation is characterized by comprising the pramipexole dihydrochloride solid preparation, isopropanol, dimethyl sulfoxide, acetonitrile and a buffer solution with the pH value of 3.0, wherein the pramipexole dihydrochloride solid preparation does not need to be ground.
2. A method of preparing the pramipexole dihydrochloride solution according to claim 1, comprising 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.
3. The preparation method of claim 2, wherein the pramipexole dihydrochloride solid preparation is allowed to stand for 3-7 min after isopropanol is added, and the time of magnetic stirring or magnetic stirring plus ultrasound after the dimethyl sulfoxide is added is 15-25 min.
4. The preparation method of 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 30-100 min, preferably 50-70 min; in the step, the centrifugation time 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.
5. The preparation method according to any one of claims 2 to 4, wherein the pramipexole dihydrochloride solid preparation has a mass of isopropanol, a volume of dimethyl sulfoxide, and a mass of (10-70 m L) and (10-70 m L), and the mass of the pramipexole dihydrochloride solid preparation is calculated based on the mass of pramipexole dihydrochloride serving as a raw material in a tablet.
6. The formulation of claim 5, wherein said pramipexole dihydrochloride solid formulation comprises pramipexole dihydrochloride tablets, sustained release tablets, or enteric coated tablets.
7. The method of claim 6, wherein the pramipexole dihydrochloride solution prepared by the method is used for quality control of API in pramipexole dihydrochloride solid preparations.
8. A method for detecting pramipexole dihydrochloride in a pramipexole dihydrochloride sustained-release solid preparation is characterized by comprising the following steps of (1) preparing a solution, respectively preparing a blank solution, a blank auxiliary material solution, a pramipexole dihydrochloride reference solution and a pramipexole dihydrochloride sample solution, wherein the blank solution comprises isopropanol, dimethyl sulfoxide and a diluent, the blank auxiliary material solution is prepared from blank auxiliary materials, isopropanol, dimethyl sulfoxide and the diluent, the blank auxiliary materials are all substances except pramipexole dihydrochloride in the pramipexole dihydrochloride solid preparation, the pramipexole dihydrochloride reference solution is prepared from pramipexole dihydrochloride monohydrate, isopropanol, dimethyl sulfoxide and the diluent, the pramipexole dihydrochloride sample solution is prepared by the preparation method according to claims 2-7, and (2) determining the prepared solution by using an HP L C determination method.
9. The detection method according to claim 8, wherein the HP L C is determined by injecting the blank solution, the pramipexole hydrochloride control solution and the pramipexole hydrochloride sample solution into a liquid chromatograph, and recording a chromatogram under the conditions of chromatographic column Inertsil ODS-3V (150 × 4.6.6 mm) and 5 μm, flow rate of 1.5 +/-0.2 m L/min, column temperature of 40 +/-3 ℃, sample temperature of 25 ℃, sample injection volume of 100 μ l, running time of 20min, detection wavelength of 264nm and A-B mobile phase for gradient elution.
10. The assay of claim 9, wherein the mobile phase a is a ph3.0 buffer; the mobile phase B is the volume of the mobile phase A: the volume of the acetonitrile is 50: 50; the diluent is acetonitrile volume: mobile phase a volume was 20: 80; the mobile phase gradient process is as follows:
the buffer solution consists of potassium dihydrogen phosphate, sodium octane sulfonate and phosphoric acid.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010362116.5A CN111487348B (en) | 2020-04-30 | 2020-04-30 | Pramipexole dihydrochloride solution prepared by pramipexole dihydrochloride solid preparation and determination method thereof |
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| CN112858527A (en) * | 2021-03-08 | 2021-05-28 | 成都倍特药业股份有限公司 | Detection method of related substances of pramipexole dihydrochloride sustained-release tablets |
| CN113466376A (en) * | 2021-07-05 | 2021-10-01 | 诺峰药业(成都)有限公司 | Cleanness verification method for pramipexole dihydrochloride production equipment |
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| CN112858527A (en) * | 2021-03-08 | 2021-05-28 | 成都倍特药业股份有限公司 | Detection method of related substances of pramipexole dihydrochloride sustained-release tablets |
| CN112858527B (en) * | 2021-03-08 | 2022-11-01 | 成都倍特药业股份有限公司 | Detection method of related substances of pramipexole dihydrochloride sustained-release tablets |
| CN113466376A (en) * | 2021-07-05 | 2021-10-01 | 诺峰药业(成都)有限公司 | Cleanness verification method for pramipexole dihydrochloride production equipment |
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