CN114740101A - Method for detecting impurities in pregabalin pharmaceutical composition - Google Patents
Method for detecting impurities in pregabalin pharmaceutical composition Download PDFInfo
- Publication number
- CN114740101A CN114740101A CN202210242044.XA CN202210242044A CN114740101A CN 114740101 A CN114740101 A CN 114740101A CN 202210242044 A CN202210242044 A CN 202210242044A CN 114740101 A CN114740101 A CN 114740101A
- Authority
- CN
- China
- Prior art keywords
- pregabalin
- mobile phase
- impurity
- pharmaceutical composition
- sample
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
- 239000012535 impurity Substances 0.000 title claims abstract description 55
- AYXYPKUFHZROOJ-ZETCQYMHSA-N pregabalin Chemical compound CC(C)C[C@H](CN)CC(O)=O AYXYPKUFHZROOJ-ZETCQYMHSA-N 0.000 title claims abstract description 46
- 229960001233 pregabalin Drugs 0.000 title claims abstract description 45
- 238000000034 method Methods 0.000 title claims abstract description 22
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 17
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims abstract description 27
- 239000012488 sample solution Substances 0.000 claims abstract description 22
- 239000000523 sample Substances 0.000 claims abstract description 14
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 13
- 238000005303 weighing Methods 0.000 claims abstract description 12
- QEVHRUUCFGRFIF-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C(C5=CC=C(OC)C=C5N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 QEVHRUUCFGRFIF-MDEJGZGSSA-N 0.000 claims abstract description 11
- 238000010828 elution Methods 0.000 claims abstract description 10
- XUKUURHRXDUEBC-SXOMAYOGSA-N (3s,5r)-7-[2-(4-fluorophenyl)-3-phenyl-4-(phenylcarbamoyl)-5-propan-2-ylpyrrol-1-yl]-3,5-dihydroxyheptanoic acid Chemical compound C=1C=CC=CC=1C1=C(C=2C=CC(F)=CC=2)N(CC[C@@H](O)C[C@H](O)CC(O)=O)C(C(C)C)=C1C(=O)NC1=CC=CC=C1 XUKUURHRXDUEBC-SXOMAYOGSA-N 0.000 claims abstract description 9
- AAEQXEDPVFIFDK-UHFFFAOYSA-N 3-(4-fluorobenzoyl)-2-(2-methylpropanoyl)-n,3-diphenyloxirane-2-carboxamide Chemical compound C=1C=CC=CC=1NC(=O)C1(C(=O)C(C)C)OC1(C=1C=CC=CC=1)C(=O)C1=CC=C(F)C=C1 AAEQXEDPVFIFDK-UHFFFAOYSA-N 0.000 claims abstract description 9
- 239000008055 phosphate buffer solution Substances 0.000 claims abstract description 8
- 238000002360 preparation method Methods 0.000 claims abstract description 6
- 238000004811 liquid chromatography Methods 0.000 claims abstract description 5
- 239000000843 powder Substances 0.000 claims description 14
- 239000012528 membrane Substances 0.000 claims description 13
- 239000000243 solution Substances 0.000 claims description 13
- 238000001514 detection method Methods 0.000 claims description 12
- 239000007787 solid Substances 0.000 claims description 11
- 238000000227 grinding Methods 0.000 claims description 8
- 239000002033 PVDF binder Substances 0.000 claims description 5
- 239000004695 Polyether sulfone Substances 0.000 claims description 5
- 238000005119 centrifugation Methods 0.000 claims description 5
- 229920006393 polyether sulfone Polymers 0.000 claims description 5
- 229920002981 polyvinylidene fluoride Polymers 0.000 claims description 5
- 239000002775 capsule Substances 0.000 claims description 4
- 238000001914 filtration Methods 0.000 claims description 4
- 239000007788 liquid Substances 0.000 claims description 4
- 239000004570 mortar (masonry) Substances 0.000 claims description 4
- 238000002347 injection Methods 0.000 claims description 3
- 239000007924 injection Substances 0.000 claims description 3
- 238000009210 therapy by ultrasound Methods 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 5
- 229940079593 drug Drugs 0.000 abstract description 4
- 230000014759 maintenance of location Effects 0.000 description 10
- 230000000052 comparative effect Effects 0.000 description 4
- BTCSSZJGUNDROE-UHFFFAOYSA-N gamma-aminobutyric acid Chemical compound NCCCC(O)=O BTCSSZJGUNDROE-UHFFFAOYSA-N 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- 239000012496 blank sample Substances 0.000 description 3
- 239000008363 phosphate buffer Substances 0.000 description 3
- OGNSCSPNOLGXSM-UHFFFAOYSA-N (+/-)-DABA Natural products NCCC(N)C(O)=O OGNSCSPNOLGXSM-UHFFFAOYSA-N 0.000 description 2
- IWYDHOAUDWTVEP-ZETCQYMHSA-N (S)-mandelic acid Chemical compound OC(=O)[C@@H](O)C1=CC=CC=C1 IWYDHOAUDWTVEP-ZETCQYMHSA-N 0.000 description 2
- UATSLDZQNXAKMA-UHFFFAOYSA-N 3-(2-methylpropyl)pentanedioic acid Chemical compound CC(C)CC(CC(O)=O)CC(O)=O UATSLDZQNXAKMA-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- 229960003692 gamma aminobutyric acid Drugs 0.000 description 2
- 239000000203 mixture Substances 0.000 description 2
- 208000004296 neuralgia Diseases 0.000 description 2
- 208000021722 neuropathic pain Diseases 0.000 description 2
- 238000012856 packing Methods 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 229910052710 silicon Inorganic materials 0.000 description 2
- 239000010703 silicon Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- RTGDFNSFWBGLEC-TVPGTPATSA-N 2-morpholin-4-ylethyl (z)-6-(4-hydroxy-6-methoxy-7-methyl-3-oxo-1h-2-benzofuran-5-yl)-4-methylhex-4-enoate Chemical compound COC1=C(C)C=2COC(=O)C=2C(O)=C1C\C=C(\C)CCC(=O)OCCN1CCOCC1 RTGDFNSFWBGLEC-TVPGTPATSA-N 0.000 description 1
- 208000019901 Anxiety disease Diseases 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- 208000032131 Diabetic Neuropathies Diseases 0.000 description 1
- 229920012266 Poly(ether sulfone) PES Polymers 0.000 description 1
- 206010036376 Postherpetic Neuralgia Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 239000012491 analyte Substances 0.000 description 1
- 230000036506 anxiety Effects 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 150000001875 compounds Chemical class 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 206010015037 epilepsy Diseases 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 230000003993 interaction Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 150000003951 lactams Chemical class 0.000 description 1
- 238000005374 membrane filtration Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 238000002161 passivation Methods 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 238000002203 pretreatment Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 238000005070 sampling Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
Images
Classifications
-
- 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
-
- 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
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/06—Preparation
-
- 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
- G01N30/86—Signal analysis
- G01N30/8675—Evaluation, i.e. decoding of the signal into analytical information
- G01N30/8679—Target compound analysis, i.e. whereby a limited number of peaks is analysed
-
- 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
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/06—Preparation
- G01N2030/065—Preparation using different phases to separate parts of sample
Landscapes
- Physics & Mathematics (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Engineering & Computer Science (AREA)
- Library & Information Science (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The application relates to a method for detecting impurities in a pregabalin pharmaceutical composition, which comprises the following steps: preparation of a sample solution: weighing a certain amount of sample, dissolving the sample in water, and fixing the volume to form a sample solution for later use; detecting impurities in the sample solution by using liquid chromatography, wherein a chromatographic column is Hypersil BDS C18, gradient elution is carried out by using a mobile phase A and a mobile phase B, the mobile phase A is phosphate buffer solution, and the mobile phase B is methanol; wherein the impurities comprise impurity A, impurity B, impurity C and impurity D. The method can separate four known impurities in the pregabalin drug, thereby effectively controlling the quality of the pregabalin drug and reducing the harm to human bodies.
Description
Technical Field
The application relates to the field of analytical chemistry, in particular to a method for detecting impurities in a pregabalin pharmaceutical composition.
Background
Pregabalin is a novel gamma-aminobutyric acid (GABA) receptor agonist useful for the treatment of neuropathic pain, regional seizure epilepsy and anxiety. The U.S. Food and Drug Administration (FDA) approved by the U.S. food and drug administration (12 months 2004) for the treatment of neuropathic pain and postherpetic neuralgia of diabetic peripheral neuropathy Pregabalin is chemically (S) -3- (aminomethyl) -5-methylhexanoic acid, and has a molecular formula of C8H17NO2Having a structural formula of
Is white or off-white crystalline solid, and has the characteristics of being easily dissolved in water, alkaline and acidic aqueous solutions.
In the finished product of pregabalin, there are raw material residues or impurity residues generated in the preparation process, such as S-mandelic acid, isobutyl glutaric acid and the like, and the content of the impurities generates toxicity once being excessive, thereby causing harm to human bodies, but the detection and control of the impurities cannot be carried out at present.
Content of application
In order to overcome the defects, the application provides a detection method of impurities in a pregabalin pharmaceutical composition, and the detection method can separate four known impurities in the pregabalin pharmaceutical composition, so that the quality of the pregabalin pharmaceutical composition can be effectively controlled, and the harm to a human body caused by the quality of the pregabalin pharmaceutical composition is reduced.
The technical scheme adopted by the application for solving the technical problem is as follows:
a method for detecting impurities in a pregabalin pharmaceutical composition comprises the following steps:
step 1: preparation of a sample solution: weighing a certain amount of sample, dissolving the sample in water, and fixing the volume to form a sample solution for later use;
step 2: detecting impurities in the sample solution by using liquid chromatography, wherein a chromatographic column is Hypersil BDS C18, gradient elution is carried out by using a mobile phase A and a mobile phase B, the mobile phase A is phosphate buffer solution, and the mobile phase B is methanol;
wherein the impurities comprise impurity A, impurity B, impurity C and impurity D;
preferably, the step 1 specifically comprises the following steps:
1a, weighing a certain amount of solid contents of pregabalin capsules or pregabalin tablets, putting the solid contents or the pregabalin tablets into a mortar for grinding, and grinding into uniform powder;
1b, weighing a certain amount of powder in a volumetric flask, adding a certain amount of water, ultrasonically dissolving the powder, fixing the volume to the scale of the volumetric flask by using the water, and shaking up;
1c, filtering or centrifuging the solution with constant volume by using a filter membrane to obtain a sample solution.
Preferably, in the step 1b, each 1mL of the solution after volume metering contains 5-10mg of pregabalin, and the ultrasonic time is 10-30 min.
Preferably, in the step 1c, the filter membrane is a polyethersulfone filter membrane or a polyvinylidene fluoride filter membrane, and the centrifugation conditions are as follows: the rotating speed of the centrifuge is 5500-6500rpm/min, and the centrifugation time is 10-15 min.
Preferably, the detection conditions of the liquid chromatography in step 2 are: the detection wavelength is 210nm, the column temperature is 35 +/-5 ℃, the flow rate of the mobile phase is 1.0 +/-0.1 mL/min, and the sample injection amount is as follows: 20-50 μ L.
Preferably, the phosphate buffer pH is 6.3 ± 0.1.
Preferably, the conditions for gradient elution of the mobile phase A and the mobile phase B are as follows:
| time (min) | Mobile phase A (v%) | Mobile phase B, (v%) |
| 0 | 90 | 10 |
| 4 | 90 | 10 |
| 30 | 40 | 60 |
| 35 | 40 | 60 |
| 36 | 90 | 10 |
| 50 | 90 | 10 |
。
The beneficial effect of this application is: in the application, a Hypersil BDS C18 chromatographic column is adopted, a mixture of a phosphate buffer solution and methanol is used as a mobile phase, and the phosphate buffer solution and the methanol adopt a gradient elution method, so that the pregabalin, the impurity A, the impurity B, the impurity C and the impurity D can be separated, and a blank sample does not have any impurity peak, so that the quality of the pregabalin medicine is effectively controlled, and the harm to a human body is reduced; in the process of preparing the sample solution, the ultrasonic dissolution is utilized, and pretreatment methods such as filter membrane filtration or centrifugal separation are carried out on the solution, so that the obtained sample solution is free of interfering substances, and the accurate detection of subsequent sample HPLC is facilitated.
Drawings
FIG. 1 is a chromatogram of example 1 of the present application;
FIG. 2 is a chromatogram of comparative example 1 of the present application.
Detailed Description
The technical solutions in the embodiments of the present application will be clearly and completely described below with reference to the embodiments of the present application, and it is obvious that the described embodiments are only a part of the embodiments of the present application, and not all of the embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present application.
A method for detecting impurities in a pregabalin pharmaceutical composition comprises the following steps:
step 1: sample solution preparation: weighing a certain amount of sample, dissolving the sample in water, and fixing the volume to form a sample solution for later use;
step 2: detecting impurities in the sample solution by using liquid chromatography, wherein a chromatographic column is Hypersil BDS C18, gradient elution is carried out by using a mobile phase A and a mobile phase B, the mobile phase A is phosphate buffer solution, and the mobile phase B is methanol; hypersil BDS chromatographic packing is excellent reverse phase column packing, has good durability and reproducibility, and has wide application range, the residual silicon hydroxyl is reduced to the limit through special alkali passivation treatment before the Hypersil BDS silica gel supporter is bonded, the improved surface ensures that the bonded silica gel has high coordination degree, the interaction between the silicon hydroxyl and an analyte is greatly reduced, the chromatographic peak type is improved, the tailing degree of the chromatographic peak is reduced, and the symmetry of the peak is improved, the Hypersil BDS chromatographic column bonding phase has four groups of C18, C8, phenyl and cyano, and after a plurality of tests, the Hypersil BDS C18 is adopted to well separate the impurity A, the impurity B, the impurity C and the impurity D in the Pregabalin; the specific specification of the chromatographic column in the application is as follows: hypersil BDS C18, 4.6 × 250mm, 5 μm;
wherein the impurities comprise impurity A, impurity B, impurity C and impurity D;
The step 1 specifically comprises the following processes:
1a, weighing a certain amount of solid contents of pregabalin capsules or pregabalin tablets, putting the solid contents or the pregabalin tablets into a mortar for grinding, and grinding into uniform powder;
1b, weighing a certain amount of powder in a volumetric flask, adding a certain amount of water, ultrasonically dissolving the powder, fixing the volume to the scale of the volumetric flask by using the water, and shaking up;
1c, filtering or centrifuging the solution with constant volume by using a filter membrane to obtain a sample solution.
In the step 1b, the pregabalin is contained in every 1mL of the solution after volume fixing, and the ultrasonic time is 10-30 min. For example, if the weighed powder contains 500mg of pregabalin and the volume is determined in a 50mL volumetric flask, 10mg of pregabalin per 1mL is obtained.
In the step 1c, the filter membrane is a polyethersulfone filter membrane or a polyvinylidene fluoride filter membrane, and the centrifugal treatment conditions are as follows: the rotating speed of the centrifuge is 5500-6500rpm/min, and the centrifugation time is 10-15 min. The solution is filtered or centrifuged using a Polyethersulfone (PES) filter or a polyvinylidene fluoride filter (PVDF) filter to remove small particles from the solution.
The detection conditions of the liquid chromatogram in the step 2 are as follows: the detection wavelength is 210nm, the column temperature is 35 +/-5 ℃, the flow rate of the mobile phase is 1.0 +/-0.1 mL/min, and the sample injection amount is as follows: 20-50 mu L. The pH value of the phosphate buffer solution is 6.3 +/-0.1.
The conditions for gradient elution of the mobile phase A and the mobile phase B are as follows:
| time (min) | Mobile phase a, (v%) | Mobile phase B, (v%) |
| 0 | 90 | 10 |
| 4 | 90 | 10 |
| 30 | 40 | 60 |
| 35 | 40 | 60 |
| 36 | 90 | 10 |
| 50 | 90 | 10 |
。
Example 1:
apparatus and conditions
High performance liquid chromatograph: waters e2695 or ARC series;
a chromatographic column: hypersil BDS C18, 4.6 × 250mm, 5 μm;
mobile phase A: phosphate buffer pH 6.3, mobile phase B: methanol;
elution was carried out with the following concentration gradient
| Time (min) | Mobile phase a, (v%) | Mobile phase B, (v%) |
| 0 | 90 | 10 |
| 4 | 90 | 10 |
| 30 | 40 | 60 |
| 35 | 40 | 60 |
| 36 | 90 | 10 |
| 50 | 90 | 10 |
Flow rate: 1.0mL/min of the reaction solution,
detection wavelength: the wavelength of the light beam is 210nm,
column temperature: at a temperature of 35 c,
sample introduction amount: 20 mu L of the solution;
the experimental steps are as follows:
step 1: preparation of a sample solution:
1a, weighing a certain amount of solid contents of pregabalin capsules, putting the solid contents into a mortar for grinding, and grinding the solid contents into uniform powder;
1b, weighing a certain amount of powder in a 50mL volumetric flask, wherein the powder contains 500mg of pregabalin, adding a certain amount of water, ultrasonically dissolving the powder, fixing the volume to the scale of the volumetric flask by using the water, and shaking up;
1c, filtering the solution with constant volume by using a PES (polyether sulfone) filter membrane to obtain a sample solution;
and 2, step: a sampling needle sucks 20 mu L of sample solution, and the sample solution is injected into a sample inlet of a liquid chromatograph to detect impurities in the sample solution, so that a chromatogram map shown in the figure 1 is obtained;
in fig. 1, the chromatographic peak with the retention time of 3.821min is impurity C (EP impurity C in the figure), the chromatographic peak with the retention time of 6.610min is pregabalin (pregabalin in the figure), the chromatographic peak with the retention time of 15.507min is impurity B (isobutylglutatic acid in the figure), the chromatographic peak with the retention time of 24.880min is impurity a (EP impurity a in the figure), and the chromatographic peak with the retention time of 27.602min is impurity D (EP impurity D in the figure), so that the method can completely separate the known four impurities, and no interference peak of the impurities exists in the blank sample.
Comparative example 1:
comparative example 1 differs from example 1 in that:
mobile phase a of comparative example 1: phosphate buffer (ph 6.5): methanol 80:20, mobile phase B: methanol: acetonitrile 10:90, in volume ratio, and elution was performed with the following concentration gradient:
obtaining the chromatogram of FIG. 2;
in fig. 2, a chromatographic peak with a retention time of 3.808min is impurity C, a chromatographic peak with a retention time of 5.716min is pregabalin, a chromatographic peak with a retention time of 14.486min is impurity B, a chromatographic peak with a retention time of 23.566min is impurity a, and a chromatographic peak with a retention time of 31.578min is impurity D, although the method can completely separate known four impurities, an interference peak appears at 19.666min in a blank sample, and therefore, the detection of other single impurities can be influenced.
It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the concept of the present application, which falls within the scope of protection of the present application. Therefore, the protection scope of the present patent shall be subject to the appended claims.
Claims (7)
1. A method for detecting impurities in a pregabalin pharmaceutical composition is characterized by comprising the following steps: the method comprises the following steps:
step 1: preparation of a sample solution: weighing a certain amount of sample, dissolving the sample in water, and fixing the volume to form a sample solution for later use;
step 2: detecting impurities in the sample solution by using liquid chromatography, wherein a chromatographic column is Hypersil BDS C18, gradient elution is carried out by using a mobile phase A and a mobile phase B, the mobile phase A is phosphate buffer solution, and the mobile phase B is methanol;
wherein the impurities comprise impurity A, impurity B, impurity C and impurity D;
2. the method for detecting impurities in a pregabalin pharmaceutical composition according to claim 1, characterized in that: the step 1 specifically comprises the following processes:
1a, weighing a certain amount of solid contents of pregabalin capsules or pregabalin tablets, putting the solid contents or pregabalin tablets into a mortar for grinding, and grinding the solid contents or pregabalin tablets into uniform powder;
1b, weighing a certain amount of powder in a volumetric flask, adding a certain amount of water, ultrasonically dissolving the powder, fixing the volume to the scale of the volumetric flask by using the water, and shaking up;
1c, filtering or centrifuging the solution with constant volume by using a filter membrane to obtain a sample solution.
3. The method for detecting impurities in a pregabalin pharmaceutical composition according to claim 2, characterized in that: in the step 1b, the pregabalin is contained in each 1mL of the solution after constant volume, and the ultrasonic treatment time is 10-30 min.
4. The method for detecting impurities in the pregabalin pharmaceutical composition according to claim 2, wherein: in the step 1c, the filter membrane is a polyethersulfone filter membrane or a polyvinylidene fluoride filter membrane, and the centrifugation conditions are as follows: the rotating speed of the centrifuge is 5500-6500rpm/min, and the centrifugation time is 10-15 min.
5. The method for detecting impurities in a pregabalin pharmaceutical composition according to claim 1, characterized in that: the detection conditions of the liquid chromatogram in the step 2 are as follows: the detection wavelength is 210nm, the column temperature is 35 +/-5 ℃, the flow rate of the mobile phase is 1.0 +/-0.1 mL/min, and the sample injection amount is as follows: 20-50 mu L.
6. The method for detecting impurities in the pregabalin pharmaceutical composition according to claim 1, wherein: the pH of the phosphate buffer solution is 6.3 +/-0.1.
7. The method for detecting impurities in the pregabalin pharmaceutical composition according to claim 1, wherein: the conditions for gradient elution of the mobile phase A and the mobile phase B are as follows:
。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210242044.XA CN114740101B (en) | 2022-03-11 | 2022-03-11 | Method for detecting impurities in pregabalin pharmaceutical composition |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210242044.XA CN114740101B (en) | 2022-03-11 | 2022-03-11 | Method for detecting impurities in pregabalin pharmaceutical composition |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN114740101A true CN114740101A (en) | 2022-07-12 |
| CN114740101B CN114740101B (en) | 2023-11-21 |
Family
ID=82275402
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210242044.XA Active CN114740101B (en) | 2022-03-11 | 2022-03-11 | Method for detecting impurities in pregabalin pharmaceutical composition |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114740101B (en) |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090137842A1 (en) * | 2007-10-03 | 2009-05-28 | Vollerner Yuri | Pregabalin -4-eliminate, pregabalin 5-eliminate, their use as reference marker and standard, and method to produce pregabalin containing low levels thereof |
| CN104710320A (en) * | 2015-03-30 | 2015-06-17 | 浙江华海药业股份有限公司 | Method for preparing pregabalin |
| CN111929370A (en) * | 2020-02-28 | 2020-11-13 | 中国人民解放军军事科学院军事医学研究院 | Method for detecting related substances in pregabalin oral solution |
| CN112798722A (en) * | 2020-12-29 | 2021-05-14 | 浙江和泽医药科技股份有限公司 | Method for determining degradation impurities and auxiliary materials in pregabalin oral solution by using HPLC (high Performance liquid chromatography) method |
| CN113075301A (en) * | 2020-01-04 | 2021-07-06 | 北京万全德众医药生物技术有限公司 | Method for separating and measuring pregabalin raw material and preparation thereof by liquid chromatography |
-
2022
- 2022-03-11 CN CN202210242044.XA patent/CN114740101B/en active Active
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20090137842A1 (en) * | 2007-10-03 | 2009-05-28 | Vollerner Yuri | Pregabalin -4-eliminate, pregabalin 5-eliminate, their use as reference marker and standard, and method to produce pregabalin containing low levels thereof |
| CN104710320A (en) * | 2015-03-30 | 2015-06-17 | 浙江华海药业股份有限公司 | Method for preparing pregabalin |
| CN113075301A (en) * | 2020-01-04 | 2021-07-06 | 北京万全德众医药生物技术有限公司 | Method for separating and measuring pregabalin raw material and preparation thereof by liquid chromatography |
| CN111929370A (en) * | 2020-02-28 | 2020-11-13 | 中国人民解放军军事科学院军事医学研究院 | Method for detecting related substances in pregabalin oral solution |
| CN112798722A (en) * | 2020-12-29 | 2021-05-14 | 浙江和泽医药科技股份有限公司 | Method for determining degradation impurities and auxiliary materials in pregabalin oral solution by using HPLC (high Performance liquid chromatography) method |
Also Published As
| Publication number | Publication date |
|---|---|
| CN114740101B (en) | 2023-11-21 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN110687229A (en) | Diclofenac sodium raw material and analysis method of related substances in preparation thereof | |
| CN106749101B (en) | A kind of preparation method of difenidol hydrochloride | |
| CN109387587B (en) | Detection method of L-2-amino-5-guanidino valeric acid enantiomer | |
| CN114740101B (en) | Method for detecting impurities in pregabalin pharmaceutical composition | |
| TW202012433A (en) | A preparation method of precursor recombinant human insulin or analog thereof | |
| CN106706769B (en) | Separation and determination method of empagliflozin and optical isomer thereof | |
| CN101609069A (en) | A kind of method of measuring Entecavir and Pharmaceutical composition related substance thereof with the HPLC method | |
| CN115372497B (en) | Method for measuring content of 6 alkaloid components in small collateral-activating pills | |
| CN104829694B (en) | A kind of purification process of pitutrin | |
| CN110579541B (en) | Detection method of lansoprazole related substances | |
| CN108760931A (en) | A kind of high-efficiency liquid chromatography method for detecting of tyrasamine | |
| CN111220720B (en) | Purity detection method for trypsin and zymogen thereof | |
| CN114295764B (en) | Gel related substance detection method | |
| CN114137120A (en) | Method for detecting related substances in rapamycin drug stent | |
| CN109096367B (en) | Separation and purification method of impurity G generated in reduced glutathione fermentation process and application thereof | |
| Hutchins et al. | Determination of ampicillin in serum by using simple ultrafiltration technique and liquid chromatographic analysis | |
| CN1947740A (en) | Single herb medicine, intermediate and its injection liquid finger-print atlas quality testing method | |
| CN116008439B (en) | Method for detecting impurities in 2, 6-dioxaspiro [4,5] decane compounds or salts thereof | |
| CN114609256B (en) | Method for detecting pesticide residue in liquid dairy product | |
| CN114295747B (en) | Analysis method of Parami Wei Qishi material and impurities | |
| CN110850012B (en) | Detection method of 1- (2, 3-dichlorophenyl) piperazine hydrochloride and related substances thereof | |
| CN108658905B (en) | Method for reducing related substances in potassium sodium dehydroandroan drographolide succinate raw material medicine finished product | |
| CN109115913B (en) | HPLC method for separating ramosetron hydrochloride and S-type enantiomer thereof based on conventional phenyl chromatographic column | |
| CN116818953A (en) | Analysis method of Parami Wei Qishi material and impurity A | |
| CN1584025A (en) | Method for extracting cydonic chimosin |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| CB02 | Change of applicant information |
Address after: 215300 191 Jinyang West Road, Lujia Town, Kunshan City, Suzhou City, Jiangsu Province Applicant after: Dequan Pharmaceutical (Jiangsu) Co.,Ltd. Address before: 215300 191 Jinyang West Road, Lujia Town, Kunshan City, Suzhou City, Jiangsu Province Applicant before: YUNG SHIN PHARM.IND.(KUNSHAN) CO.,LTD. |
|
| CB02 | Change of applicant information | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |