CN114199812A - Method for detecting memantine hydrochloride in memantine hydrochloride sustained-release preparation - Google Patents
Method for detecting memantine hydrochloride in memantine hydrochloride sustained-release preparation Download PDFInfo
- Publication number
- CN114199812A CN114199812A CN202111626407.1A CN202111626407A CN114199812A CN 114199812 A CN114199812 A CN 114199812A CN 202111626407 A CN202111626407 A CN 202111626407A CN 114199812 A CN114199812 A CN 114199812A
- Authority
- CN
- China
- Prior art keywords
- memantine hydrochloride
- release preparation
- memantine
- detecting
- hydrochloride sustained
- 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.)
- Pending
Links
- LDDHMLJTFXJGPI-UHFFFAOYSA-N memantine hydrochloride Chemical compound Cl.C1C(C2)CC3(C)CC1(C)CC2(N)C3 LDDHMLJTFXJGPI-UHFFFAOYSA-N 0.000 title claims abstract description 116
- 229960000967 memantine hydrochloride Drugs 0.000 title claims abstract description 109
- 239000003405 delayed action preparation Substances 0.000 title claims abstract description 44
- 238000000034 method Methods 0.000 title claims description 18
- 238000001514 detection method Methods 0.000 claims abstract description 33
- 238000002329 infrared spectrum Methods 0.000 claims abstract description 33
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 32
- 238000002156 mixing Methods 0.000 claims abstract description 29
- 239000007788 liquid Substances 0.000 claims abstract description 26
- 150000001335 aliphatic alkanes Chemical class 0.000 claims abstract description 12
- 239000002904 solvent Substances 0.000 claims abstract description 8
- 239000003513 alkali Substances 0.000 claims abstract description 7
- 238000000605 extraction Methods 0.000 claims abstract description 7
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 24
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 claims description 22
- 238000000227 grinding Methods 0.000 claims description 18
- 238000002360 preparation method Methods 0.000 claims description 14
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 13
- 238000001035 drying Methods 0.000 claims description 12
- 238000001228 spectrum Methods 0.000 claims description 10
- 238000002834 transmittance Methods 0.000 claims description 9
- 239000002775 capsule Substances 0.000 claims description 8
- 238000013268 sustained release Methods 0.000 claims description 8
- 239000012730 sustained-release form Substances 0.000 claims description 8
- 239000002585 base Substances 0.000 claims description 7
- 229960004640 memantine Drugs 0.000 claims description 7
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 6
- 238000005119 centrifugation Methods 0.000 claims description 6
- 150000001924 cycloalkanes Chemical class 0.000 claims description 6
- 239000007939 sustained release tablet Substances 0.000 claims description 3
- 230000003113 alkalizing effect Effects 0.000 claims description 2
- 239000003826 tablet Substances 0.000 claims description 2
- 239000000523 sample Substances 0.000 description 31
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 9
- 239000000243 solution Substances 0.000 description 9
- 230000000052 comparative effect Effects 0.000 description 8
- 239000002244 precipitate Substances 0.000 description 8
- 239000012188 paraffin wax Substances 0.000 description 6
- 239000000843 powder Substances 0.000 description 6
- 239000000047 product Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 238000004566 IR spectroscopy Methods 0.000 description 4
- 239000007864 aqueous solution Substances 0.000 description 4
- 238000004090 dissolution Methods 0.000 description 4
- 239000013558 reference substance Substances 0.000 description 4
- 208000024827 Alzheimer disease Diseases 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 239000013074 reference sample Substances 0.000 description 3
- GXDHCNNESPLIKD-UHFFFAOYSA-N 2-methylhexane Natural products CCCCC(C)C GXDHCNNESPLIKD-UHFFFAOYSA-N 0.000 description 2
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 2
- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 2
- DMEGYFMYUHOHGS-UHFFFAOYSA-N cycloheptane Chemical compound C1CCCCCC1 DMEGYFMYUHOHGS-UHFFFAOYSA-N 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 238000004811 liquid chromatography Methods 0.000 description 2
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 2
- 230000035945 sensitivity Effects 0.000 description 2
- LRMSQVBRUNSOJL-UHFFFAOYSA-N 2,2,3,3,3-pentafluoropropanoic acid Chemical compound OC(=O)C(F)(F)C(F)(F)F LRMSQVBRUNSOJL-UHFFFAOYSA-N 0.000 description 1
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- NHTMVDHEPJAVLT-UHFFFAOYSA-N Isooctane Chemical compound CC(C)CC(C)(C)C NHTMVDHEPJAVLT-UHFFFAOYSA-N 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- 206010039966 Senile dementia Diseases 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 238000007792 addition Methods 0.000 description 1
- 238000000149 argon plasma sintering Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- WJTCGQSWYFHTAC-UHFFFAOYSA-N cyclooctane Chemical compound C1CCCCCCC1 WJTCGQSWYFHTAC-UHFFFAOYSA-N 0.000 description 1
- 239000004914 cyclooctane Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- JVSWJIKNEAIKJW-UHFFFAOYSA-N dimethyl-hexane Natural products CCCCCC(C)C JVSWJIKNEAIKJW-UHFFFAOYSA-N 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000000105 evaporative light scattering detection Methods 0.000 description 1
- 230000002964 excitative effect Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 235000019359 magnesium stearate Nutrition 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 229910000402 monopotassium phosphate Inorganic materials 0.000 description 1
- 235000019796 monopotassium phosphate Nutrition 0.000 description 1
- 239000003703 n methyl dextro aspartic acid receptor blocking agent Substances 0.000 description 1
- 239000002858 neurotransmitter agent Substances 0.000 description 1
- 229910052757 nitrogen Inorganic materials 0.000 description 1
- FPLYNRPOIZEADP-UHFFFAOYSA-N octylsilane Chemical group CCCCCCCC[SiH3] FPLYNRPOIZEADP-UHFFFAOYSA-N 0.000 description 1
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 description 1
- 239000002464 receptor antagonist Substances 0.000 description 1
- 229940044551 receptor antagonist Drugs 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000004454 trace mineral analysis Methods 0.000 description 1
- 239000002912 waste gas Substances 0.000 description 1
Images
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
- G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
- G01N21/35—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light
- G01N21/3563—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light for analysing solids; Preparation of samples therefor
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
- G01N1/286—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q involving mechanical work, e.g. chopping, disintegrating, compacting, homogenising
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
- G01N1/34—Purifying; Cleaning
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
- G01N1/40—Concentrating samples
- G01N1/4077—Concentrating samples by other techniques involving separation of suspended solids
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
- G01N1/44—Sample treatment involving radiation, e.g. heat
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
- G01N1/286—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q involving mechanical work, e.g. chopping, disintegrating, compacting, homogenising
- G01N2001/2866—Grinding or homogeneising
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
- G01N1/40—Concentrating samples
- G01N1/4055—Concentrating samples by solubility techniques
- G01N2001/4061—Solvent extraction
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N21/00—Investigating or analysing materials by the use of optical means, i.e. using sub-millimetre waves, infrared, visible or ultraviolet light
- G01N21/17—Systems in which incident light is modified in accordance with the properties of the material investigated
- G01N21/25—Colour; Spectral properties, i.e. comparison of effect of material on the light at two or more different wavelengths or wavelength bands
- G01N21/31—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry
- G01N21/35—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light
- G01N21/3563—Investigating relative effect of material at wavelengths characteristic of specific elements or molecules, e.g. atomic absorption spectrometry using infrared light for analysing solids; Preparation of samples therefor
- G01N2021/3572—Preparation of samples, e.g. salt matrices
Landscapes
- Physics & Mathematics (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Immunology (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Chemical & Material Sciences (AREA)
- Pathology (AREA)
- Spectroscopy & Molecular Physics (AREA)
- Biomedical Technology (AREA)
- Molecular Biology (AREA)
- Engineering & Computer Science (AREA)
- Investigating Or Analysing Materials By Optical Means (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention provides a detection method of memantine hydrochloride in a memantine hydrochloride sustained-release preparation, which comprises the following steps: (1) mixing the memantine hydrochloride sustained-release preparation with alkali, and alkalifying to obtain an alkalinized solution; (2) extracting the alkalized liquid obtained in the step (1) by adopting an alkane solvent to obtain an extraction liquid; (3) mixing the extract obtained in the step (2) with hydrochloric acid to obtain a test sample; (4) and (4) detecting the test sample obtained in the step (3) by adopting an infrared spectrum. The qualitative detection method for memantine hydrochloride in the memantine hydrochloride sustained-release preparation provided by the invention has strong practicability, and can realize the rapid detection of the memantine hydrochloride sustained-release preparation; the detection method provided by the invention determines the characteristic peak of memantine hydrochloride, and has the advantages of simple operation, good stability and good reproducibility.
Description
Technical Field
The invention belongs to the field of detection chemistry, and particularly relates to a detection method of memantine hydrochloride in a memantine hydrochloride sustained-release preparation.
Background
Memantine hydrochloride is an N-methyl-D-aspartate (NMDA) receptor antagonist, and is mainly used for treating Alzheimer's disease (senile dementia) by delaying the release of excitatory neurotransmitter glutamate. Memantine hydrochloride is currently the only NMDA antagonist used in Alzheimer's disease.
CN104950047A discloses a method for detecting the content, dissolution rate or dissolution rate of memantine hydrochloride or analogues thereof in a medicament, and the liquid chromatography conditions adopted by the invention are as follows: the detector is a differential refraction detector; the chromatographic column filler is octyl silane bonded silica gel; the mobile phase is methanol-0.05 mol/L potassium dihydrogen phosphate solution. However, the differential refractive detector employed in the present invention has low sensitivity and is not generally used for trace analysis; and is greatly affected by the environment.
CN101034084A discloses a dissolution rate detection method of memantine hydrochloride related preparation, which adopts a high performance liquid chromatograph-evaporation light scattering detector and takes methanol-0.05% pentafluoropropionic acid solution as a mobile phase. However, the evaporative light scattering detector adopted by the invention has low sensitivity and inconvenient use, high-pressure nitrogen or air must be configured in the experiment, and some harmful waste gas is generated in the experiment.
The existing published literature mostly adopts liquid chromatography to detect the dissolution rate of the memantine hydrochloride sustained-release preparation, and no literature reports how to adopt infrared spectroscopy to qualitatively detect the memantine hydrochloride in the memantine hydrochloride sustained-release preparation. Therefore, how to provide a qualitative detection method for memantine hydrochloride in a memantine hydrochloride sustained-release preparation becomes a problem to be solved urgently at present.
Disclosure of Invention
Aiming at the defects of the prior art, the invention aims to provide a method for detecting memantine hydrochloride in a memantine hydrochloride sustained-release preparation. The detection method provided by the invention can realize qualitative detection of memantine hydrochloride in the memantine hydrochloride sustained-release preparation.
In order to achieve the purpose, the invention adopts the following technical scheme:
the invention provides a detection method of memantine hydrochloride in a memantine hydrochloride sustained-release preparation, which comprises the following steps:
(1) mixing the memantine hydrochloride sustained-release preparation with alkali, and alkalifying to obtain an alkalinized solution;
(2) extracting the alkalized liquid obtained in the step (1) by adopting an alkane solvent to obtain an extraction liquid;
(3) mixing the extract obtained in the step (2) with hydrochloric acid to obtain a test sample;
(4) and (4) detecting the test sample obtained in the step (3) by adopting an infrared spectrum.
In the invention, in the step (1), the memantine hydrochloride sustained release preparation is firstly mixed with alkali to remove lactose, magnesium stearate and other related auxiliary materials in the memantine hydrochloride sustained release preparation, and meanwhile, memantine hydrochloride is dehydrochloric acid to become memantine; in the step (2), extracting memantine by adopting an alkane solvent; in step (3), hydrochloric acid is added to convert memantine to memantine hydrochloride.
In the invention, in the step (1), the memantine hydrochloride sustained-release preparation comprises a memantine hydrochloride sustained-release capsule and/or a memantine hydrochloride sustained-release tablet.
Preferably, in step (1), the base comprises sodium hydroxide and/or potassium hydroxide, preferably sodium hydroxide.
In the invention, in the step (1), the molar ratio of the base to the memantine hydrochloride in the memantine hydrochloride sustained-release preparation is (10-30):1, and can be, for example, 10:1, 12:1, 15:1, 18:1, 20:1, 22:1, 25:1, 28:1, 30:1 and the like.
Preferably, in step (1), the molar concentration of the base is 0.5 to 1.5mol/L, and may be, for example, 0.5mol/L, 0.6mol/L, 0.7mol/L, 0.8mol/L, 0.9mol/L, 1mol/L, 1.1mol/L, 1.2mol/L, 1.3mol/L, 1.4mol/L, 1.5mol/L, or the like.
Preferably, in step (1), the alkalization temperature is 20-30 deg.C, such as 20 deg.C, 21 deg.C, 22 deg.C, 23 deg.C, 24 deg.C, 25 deg.C, 26 deg.C, 27 deg.C, 28 deg.C, 29 deg.C, 30 deg.C etc.; the time is 0.5-1.5min, such as 0.5min, 0.6min, 0.7min, 0.8min, 0.9min, 1min, 1.1min, 1.2min, 1.3min, 1.4min, 1.5min, etc.
In the present invention, in the step (2), the alkane solvent is a C6-C8 alkane and/or a C6-C8 cycloalkane, preferably a C6-C8 linear alkane, and more preferably n-hexane.
Wherein, the paraffin of C6-C8 can be C6 paraffin, C7 paraffin or C8 paraffin, can be C6-C8 straight-chain paraffin or C6-C8 branched-chain paraffin, and can be n-hexane, n-heptane, n-octane, iso-heptane, iso-octane, etc.; wherein the C6-C8 cycloalkane may be C6 cycloalkane, C7 cycloalkane or C8 cycloalkane, such as cyclohexane, cycloheptane, cyclooctane, etc.
Preferably, in the step (2), the volume ratio of the alkane solvent to the alkalizing liquid is 1 (0.5-1.5), and may be, for example, 1:0.5, 1:0.6, 1:0.7, 1:0.8, 1:0.9, 1:1, 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.5, etc.
Preferably, in step (2), the extraction temperature is 20-30 deg.C, such as 20 deg.C, 21 deg.C, 22 deg.C, 23 deg.C, 24 deg.C, 25 deg.C, 26 deg.C, 27 deg.C, 28 deg.C, 29 deg.C, 30 deg.C etc.; the time is 1.5-2.5min, such as 1.5min, 1.6min, 1.7min, 1.8min, 1.9min, 2min, 2.1min, 2.2min, 2.3min, 2.4min, 2.5min, etc.
In the present invention, in the step (3), the molar ratio of the hydrochloric acid to memantine in the extract is (3-7):1, and may be, for example, 3:1, 4:1, 5:1, 6:1, 7:1, etc.
Preferably, in the step (3), the molar concentration of the hydrochloric acid is 2-6mol/L, and may be, for example, 2mol/L, 3mol/L, 4mol/L, 5mol/L, 6mol/L, and the like.
In the present invention, step (3) further comprises centrifugation, drying and sample preparation, which are sequentially performed after the mixing.
Preferably, the rotation speed of the centrifugation is 3500-; the time is 3-5min, such as 3min, 3.2min, 3.4min, 3.6min, 3.8min, 4min, 4.2min, 4.4min, 4.6min, 4.8min, 5min, etc.
Preferably, the drying temperature is 90-120 ℃, for example, can be 90 ℃, 100 ℃, 110 ℃, 120 ℃ and so on; the time is 0.5 to 1.5 hours, and may be, for example, 0.5 hour, 0.6 hour, 0.7 hour, 0.8 hour, 0.9 hour, 1 hour, 1.1 hour, 1.2 hour, 1.3 hour, 1.4 hour, 1.5 hour, or the like.
In the invention, the sample preparation comprises the following steps: and mixing the dried sample with potassium bromide, grinding and tabletting to obtain the test sample.
Preferably, the mass ratio of the dried sample to the potassium bromide is 1 (80-120), and may be, for example, 1:80, 1:90, 1:100, 1:110, 1:120, or the like.
Preferably, the grinding time is 10-20s, and may be, for example, 10s, 11s, 12s, 13s, 14s, 15s, 16s, 17s, 18s, 19s, 20s, or the like.
Preferably, the pressure of the tablet is 80-90KN, for example, 80KN, 82KN, 84KN, 86KN, 88KN, 90KN, etc.; the time is 3-5min, such as 3min, 3.5min, 4min, 4.5min, 5min, etc.
In the invention, in the step (4), the spectrum is collected by adopting a Transmittance mode in the detection of the infrared spectrum.
Preferably, in step (4), the resolution in detection of the infrared spectrum is 3-5cm-1For example, it may be 3cm-1、4cm-1、5cm-1Etc.; the number of scanning times is 12-20, and may be, for example, 12, 13, 14, 15, 16, 17, 18, 19, 20, etc.; the scanning range is 400-4000cm-1For example, it may be 400cm-1、1000cm-1、1400cm-1、2000cm-1、2400cm-1、3000cm-1、3400cm-1、4000cm-1And the like.
In the invention, the infrared characteristic peak of memantine hydrochloride comprises 2056cm-1、1512cm-1、1456cm-1、1364cm-1、1356cm-1、1344cm-1、1190cm-1、1028cm-1。
As a preferable technical scheme of the invention, the method for detecting memantine hydrochloride in the memantine hydrochloride sustained-release preparation comprises the following steps:
(A) mixing the memantine hydrochloride sustained-release preparation with alkali, and alkalifying to obtain an alkalinized solution;
wherein the molar ratio of the base to memantine hydrochloride in the memantine hydrochloride sustained-release preparation is (10-30) to 1;
(B) extracting the alkalized liquid obtained in the step (A) by using normal hexane to obtain an extraction liquid;
(C) mixing the extract obtained in the step (B) with hydrochloric acid, and then sequentially carrying out centrifugation, drying and sample preparation to obtain a test sample;
wherein the molar ratio of the hydrochloric acid to the memantine in the extract is (3-7) to 1;
(D) detecting the test sample obtained in the step (C) by adopting an infrared spectrum;
wherein, the infrared spectrum is detected by adopting a Transmittance mode to collect the spectrum, and the resolution ratio is 3-5cm-1The scanning frequency is 12-20 times, and the scanning range is 400-4000cm-1。
Compared with the prior art, the invention has the following beneficial effects:
(1) the qualitative detection method for memantine hydrochloride in the memantine hydrochloride sustained-release preparation provided by the invention has strong practicability, and can realize the rapid detection of the memantine hydrochloride sustained-release preparation;
(2) the detection method provided by the invention determines the characteristic peak of memantine hydrochloride, and has the advantages of simple operation, good stability and good reproducibility.
Drawings
FIG. 1 is an infrared spectrum of the test article in example 1.
FIG. 2 is an infrared spectrum of the control in example 1.
FIG. 3 is an infrared spectrum of the test article in example 4.
FIG. 4 is an infrared spectrum of the test article in comparative example 1.
FIG. 5 is an infrared spectrum of the test article in comparative example 2.
Detailed Description
The technical solution of the present invention is further explained by the following embodiments. It should be understood by those skilled in the art that the examples are only for the understanding of the present invention and should not be construed as the specific limitations of the present invention.
The sources of the components in the following examples are as follows:
preparation example
Preparation of control: grinding memantine hydrochloride reference substance, mixing 2mg memantine hydrochloride reference substance and 200mg potassium bromide, grinding for 15s, tabletting, and keeping under 85KN pressure for 4min to obtain reference substance.
Example 1
The embodiment provides a detection method of memantine hydrochloride in a memantine hydrochloride sustained-release preparation, which comprises the following steps:
(1) grinding the content of the memantine hydrochloride sustained-release capsule, and mixing content powder equivalent to 20mg of memantine hydrochloride with 2mL of sodium hydroxide aqueous solution (1mol/L) to obtain alkalized liquid;
(2) extracting the alkalized liquid obtained in the step (1) by adopting 2mL of normal hexane to obtain an extract liquid;
(3) mixing the extract obtained in the step (2) with 0.1mL of hydrochloric acid solution (5mol/L), and centrifuging at 4000rpm for 4min to obtain a precipitate; drying the precipitate at 105 deg.C for 1h to obtain dried substance; then mixing 2mg of the dried product with 200mg of potassium bromide, grinding for 15s, tabletting, and keeping under the pressure of 85KN for 4min to obtain a test sample;
(4) detecting the test sample obtained in the step (3) and the reference sample obtained in the preparation example by adopting infrared spectroscopy;
wherein, the spectrum is collected by adopting a Transmittance mode in the detection of the infrared spectrum, and the resolution ratio is 4cm-1The scanning frequency is 16 times, and the scanning range is 400-4000cm-1。
FIG. 1 is an infrared spectrum of the sample of example 1, from which it can be seen that the peaks characteristic to memantine hydrochloride in the sample are all2056、1512、1456、1364、1356、1344、1190、1028cm-1(ii) a FIG. 2 is an infrared spectrum of the control in example 1, from which it can be seen that the peaks of memantine hydrochloride in the control are all 2054, 1512, 1456, 1364, 1356, 1344, 1190 and 1028cm-1。
Example 2
The embodiment provides a detection method of memantine hydrochloride in a memantine hydrochloride sustained-release preparation, which comprises the following steps:
(1) grinding the content of the memantine hydrochloride sustained-release capsule, mixing content powder equivalent to 20mg of memantine hydrochloride with 1.8mL of sodium hydroxide aqueous solution (1.1mol/L) to obtain alkalized liquid;
(2) extracting the alkalized liquid obtained in the step (1) by adopting 2.2mL of normal hexane to obtain an extract liquid;
(3) mixing the extract obtained in the step (2) with 0.12mL of hydrochloric acid solution (4.8mol/L), and centrifuging for 5min at 3500pm to obtain a precipitate; drying the precipitate at 107 deg.C for 0.9h to obtain dried substance; then mixing 2mg of the dried product with 195mg of potassium bromide, grinding for 17s, tabletting, and keeping under the pressure of 87KN for 3min to obtain a test sample;
(4) detecting the test sample obtained in the step (3) and the reference sample obtained in the preparation example by adopting infrared spectroscopy;
wherein, the spectrum is collected by adopting a Transmittance mode in the detection of the infrared spectrum, and the resolution ratio is 4cm-1The scanning frequency is 16 times, and the scanning range is 400-4000cm-1。
The IR spectra of the test and control samples of example 2 were identical to those of example 1.
Example 3
The embodiment provides a detection method of memantine hydrochloride in a memantine hydrochloride sustained-release preparation, which comprises the following steps:
(1) grinding the content of the memantine hydrochloride sustained-release capsule, mixing content powder equivalent to 20mg of memantine hydrochloride with 2.2mL of sodium hydroxide aqueous solution (0.9mol/L) to obtain alkalized liquid;
(2) extracting the alkalized liquid obtained in the step (1) by adopting 1.8mL of normal hexane to obtain an extract liquid;
(3) mixing the extract obtained in the step (2) with 0.08mL of hydrochloric acid solution (5.5mol/L), and centrifuging at 4500rpm for 3min to obtain a precipitate; drying the precipitate at 106 deg.C for 1.1h to obtain dried substance; then mixing 2mg of the dried product with 205mg of potassium bromide, grinding for 14s, tabletting, and keeping under 82KN pressure for 5min to obtain a test sample;
(4) detecting the test sample obtained in the step (3) and the reference sample obtained in the preparation example by adopting infrared spectroscopy;
wherein, the spectrum is collected by adopting a Transmittance mode in the detection of the infrared spectrum, and the resolution ratio is 4cm-1The scanning frequency is 16 times, and the scanning range is 400-4000cm-1。
The IR spectra of the test and control samples of example 3 were consistent with those of example 1.
Example 4
The embodiment provides a detection method of memantine hydrochloride in a memantine hydrochloride sustained-release preparation, which comprises the following steps:
(1) grinding the content of the memantine hydrochloride sustained-release capsule, mixing content powder equivalent to 20mg of memantine hydrochloride with 2.2mL of sodium hydroxide aqueous solution (0.9mol/L) to obtain alkalized liquid;
(2) extracting the alkalized liquid obtained in the step (1) by using 1.8mL of n-heptane to obtain an extract liquid;
(3) mixing the extract obtained in the step (2) with 0.08mL of hydrochloric acid solution (5.5mol/L), and centrifuging at 4000rpm for 5min to obtain a precipitate; drying the precipitate at 106 deg.C for 1.1h to obtain dried substance; then mixing 2mg of the dried product with 205mg of potassium bromide, grinding for 14s, tabletting, and keeping under 82KN pressure for 5min to obtain a test sample;
(4) detecting the test sample obtained in the step (3) by adopting an infrared spectrum;
wherein, the spectrum is collected by adopting a Transmittance mode in the detection of the infrared spectrum, and the resolution ratio is 4cm-1The scanning frequency is 16 times, and the scanning range is 400-4000cm-1。
As shown in the embodiment of fig. 34, and the characteristic peaks of memantine hydrochloride in the sample are 2056, 1512, 1456, 1364, 1356, 1344, 1190 and 1028cm-1(ii) a Compared with n-heptane, n-hexane has stronger volatility, and a dry substance can be obtained more easily in the sample preparation process, so that the efficiency is higher in the sample preparation.
Comparative example 1
The comparative example provides a detection method of memantine hydrochloride in a memantine hydrochloride sustained-release preparation, and the detection method comprises the following steps:
grinding the content of the memantine hydrochloride sustained-release capsule, mixing content powder equivalent to 2mg of memantine hydrochloride with 200mg of potassium bromide, grinding for 15s, tabletting, and keeping under 85KN pressure for 4min to obtain a test sample; detecting the obtained test sample by adopting an infrared spectrum;
wherein, the spectrum is collected by adopting a Transmittance mode in the detection of the infrared spectrum, and the resolution ratio is 4cm-1The scanning frequency is 16 times, and the scanning range is 400-4000cm-1。
As shown in FIG. 4, the infrared spectrum of the sample of comparative example 1 shows that the peaks of Memantine hydrochloride in the sample are 2054 and 1736cm-1(ii) a Not in accordance with the IR spectrum of the control in FIG. 2.
Comparative example 2
The comparative example provides a detection method of memantine hydrochloride in a memantine hydrochloride sustained-release preparation, and the detection method comprises the following steps:
grinding the memantine hydrochloride sustained-release tablets, and extracting sustained-release capsule content powder equivalent to 20mg of memantine hydrochloride by using 5mL of dichloromethane to obtain extract liquor; evaporating the extract liquid at room temperature, and drying at 60 deg.C for 15 min to obtain dried extract; mixing 2mg of the dried product with 200mg of potassium bromide, grinding for 15s, tabletting, and keeping under 85KN pressure for 4min to obtain a test sample; detecting the obtained test sample by adopting an infrared spectrum;
wherein, the spectrum is collected by adopting a Transmittance mode in the detection of the infrared spectrum, and the resolution ratio is 4cm-1The scanning frequency is 16 times, and the scanning range is 400-4000cm-1。
As shown in FIG. 5, the infrared spectrum of the test sample in comparative example 2 shows that the peaks of Memantine hydrochloride in the test sample are 2056, 1736, 1614, 1512, 1456, 1366, 1356 and 1190cm-1(ii) a Is not consistent with the infrared spectrum of the reference substance in FIG. 2 and is 1000--1With interference peaks in between.
The applicant states that the present invention is illustrated by the above examples of the process of the present invention, but the present invention is not limited to the above process steps, i.e. it is not meant that the present invention must rely on the above process steps to be carried out. It will be apparent to those skilled in the art that any modification of the present invention, equivalent substitutions of selected materials and additions of auxiliary components, selection of specific modes and the like, which are within the scope and disclosure of the present invention, are contemplated by the present invention.
Claims (10)
1. A detection method for memantine hydrochloride in a memantine hydrochloride sustained-release preparation is characterized by comprising the following steps:
(1) mixing the memantine hydrochloride sustained-release preparation with alkali, and alkalifying to obtain an alkalinized solution;
(2) extracting the alkalized liquid obtained in the step (1) by adopting an alkane solvent to obtain an extraction liquid;
(3) mixing the extract obtained in the step (2) with hydrochloric acid to obtain a test sample;
(4) and (4) detecting the test sample obtained in the step (3) by adopting an infrared spectrum.
2. The method for detecting memantine hydrochloride in memantine hydrochloride sustained release preparation according to claim 1, wherein in step (1), the memantine hydrochloride sustained release preparation comprises memantine hydrochloride sustained release capsules and/or memantine hydrochloride sustained release tablets;
preferably, in step (1), the base comprises sodium hydroxide and/or potassium hydroxide, preferably sodium hydroxide.
3. The method for detecting memantine hydrochloride in the memantine hydrochloride sustained-release preparation according to claim 1 or 2, wherein in the step (1), the molar ratio of the base to the memantine hydrochloride in the memantine hydrochloride sustained-release preparation is (10-30): 1;
preferably, in the step (1), the molar concentration of the alkali is 0.5-1.5 mol/L;
preferably, in the step (1), the alkalization temperature is 20-30 ℃ and the time is 0.5-1.5 min.
4. The method for detecting memantine hydrochloride in memantine hydrochloride sustained release preparation according to any one of claims 1-3, wherein in step (2), said alkane solvent is C6-C8 alkane and/or C6-C8 cycloalkane, preferably C6-C8 straight chain alkane, more preferably n-hexane;
preferably, in the step (2), the volume ratio of the alkane solvent to the alkalizing liquid is 1 (0.5-1.5);
preferably, in the step (2), the temperature of the extraction is 20-30 ℃ and the time is 1.5-2.5 min.
5. The method for detecting memantine hydrochloride in the memantine hydrochloride sustained-release preparation according to any one of claims 1-4, wherein in the step (3), the molar ratio of the hydrochloric acid to the memantine in the extract is (3-7): 1;
preferably, in the step (3), the molar concentration of the hydrochloric acid is 2-6 mol/L.
6. The method for detecting memantine hydrochloride in the memantine hydrochloride sustained release preparation according to any one of claims 1-5, wherein in the step (3), the steps of centrifugation, drying and sample preparation are sequentially carried out after the mixing;
preferably, the rotation speed of the centrifugation is 3500-;
preferably, the drying temperature is 90-120 ℃ and the drying time is 0.5-1.5 h.
7. The method for detecting memantine hydrochloride in memantine hydrochloride sustained release preparation according to claim 6, wherein the sample preparation comprises the following steps: mixing the dried sample with potassium bromide, grinding and tabletting to obtain the test sample;
preferably, the mass ratio of the dried sample to the potassium bromide is 1 (80-120);
preferably, the grinding time is 10-20 s;
preferably, the pressure of the tablet is 80-90KN, and the time is 3-5 min.
8. The method for detecting memantine hydrochloride in the memantine hydrochloride sustained release preparation according to any one of claims 1-7, characterized in that in the step (4), a transmittince mode is adopted for spectrum collection in the infrared spectrum detection;
preferably, in step (4), the resolution in detection of the infrared spectrum is 3-5cm-1The scanning frequency is 12-20 times, and the scanning range is 400-4000cm-1。
9. The method for detecting memantine hydrochloride in memantine hydrochloride sustained-release preparation according to any one of claims 1-8, wherein the infrared characteristic peak of memantine hydrochloride comprises 2056cm-1、1512cm-1、1456cm-1、1364cm-1、1356cm-1、1344cm-1、1190cm-1、1028cm-1。
10. The method for detecting memantine hydrochloride in the memantine hydrochloride sustained release preparation according to any one of claims 1-9, wherein the method comprises the following steps:
(A) mixing the memantine hydrochloride sustained-release preparation with alkali, and alkalifying to obtain an alkalinized solution;
wherein the molar ratio of the base to memantine hydrochloride in the memantine hydrochloride sustained-release preparation is (10-30) to 1;
(B) extracting the alkalized liquid obtained in the step (A) by using normal hexane to obtain an extraction liquid;
(C) mixing the extract obtained in the step (B) with hydrochloric acid, and then sequentially carrying out centrifugation, drying and sample preparation to obtain a test sample;
wherein the molar ratio of the hydrochloric acid to the memantine in the extract is (3-7) to 1;
(D) detecting the test sample obtained in the step (C) by adopting an infrared spectrum;
wherein, the infrared spectrum is detected by adopting a Transmittance mode to collect the spectrum, and the resolution ratio is 3-5cm-1The scanning frequency is 12-20 times, and the scanning range is 400-4000cm-1。
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111626407.1A CN114199812A (en) | 2021-12-28 | 2021-12-28 | Method for detecting memantine hydrochloride in memantine hydrochloride sustained-release preparation |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202111626407.1A CN114199812A (en) | 2021-12-28 | 2021-12-28 | Method for detecting memantine hydrochloride in memantine hydrochloride sustained-release preparation |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN114199812A true CN114199812A (en) | 2022-03-18 |
Family
ID=80657001
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202111626407.1A Pending CN114199812A (en) | 2021-12-28 | 2021-12-28 | Method for detecting memantine hydrochloride in memantine hydrochloride sustained-release preparation |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114199812A (en) |
Citations (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006096194A2 (en) * | 2004-06-17 | 2006-09-14 | Merz Pharma Gmbh & Co. Kgaa | Drinkable immediate release tablet made with direct compression of memantine or neramexane |
| CN101038280A (en) * | 2007-04-11 | 2007-09-19 | 山东省医药工业研究所 | HPLC-ELSD measuring method for correlated matter in memantine hydrochloride |
| CN101801911A (en) * | 2007-07-18 | 2010-08-11 | 基因里克斯(英国)有限公司 | assay methods for memantine |
| US20110105443A1 (en) * | 2008-03-07 | 2011-05-05 | Laboratories Del Dr. Esteve, S.A. | Salts of memantine and cox-inhibitors and their crystal form in the treatment of pain |
| CN103619817A (en) * | 2011-04-28 | 2014-03-05 | 百时美施贵宝公司 | Novel bicyclic nitrogen containing heteroaryl TGR5 receptor modulators |
| CN104237407A (en) * | 2014-09-12 | 2014-12-24 | 山东省医药工业研究所 | Method for detecting releasing rate of amantadine hydrochloride sustained release tablets |
| WO2016140952A1 (en) * | 2015-03-02 | 2016-09-09 | Taaneh, Inc. | Authenticated systems employing fluorescent diamond particles |
| CN108218844A (en) * | 2018-03-08 | 2018-06-29 | 合肥科大生物技术有限公司 | A kind of Memantine Paxil eutectic salts and preparation method thereof, pharmaceutical composition, application |
| CN109632702A (en) * | 2019-01-22 | 2019-04-16 | 天津中医药大学 | A kind of detection method of honeysuckle content |
| US20190169179A1 (en) * | 2016-07-07 | 2019-06-06 | Ironwood Pharmaceuticals, Inc. | Solid forms of an sgc stimulator |
| CN110845339A (en) * | 2019-11-08 | 2020-02-28 | 湖南洞庭药业股份有限公司 | Synthetic method of memantine hydrochloride |
| CN112730652A (en) * | 2020-12-17 | 2021-04-30 | 植恩生物技术股份有限公司 | Memantine hydrochloride and detection method of impurities thereof |
-
2021
- 2021-12-28 CN CN202111626407.1A patent/CN114199812A/en active Pending
Patent Citations (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2006096194A2 (en) * | 2004-06-17 | 2006-09-14 | Merz Pharma Gmbh & Co. Kgaa | Drinkable immediate release tablet made with direct compression of memantine or neramexane |
| CN101038280A (en) * | 2007-04-11 | 2007-09-19 | 山东省医药工业研究所 | HPLC-ELSD measuring method for correlated matter in memantine hydrochloride |
| CN101801911A (en) * | 2007-07-18 | 2010-08-11 | 基因里克斯(英国)有限公司 | assay methods for memantine |
| US20110105443A1 (en) * | 2008-03-07 | 2011-05-05 | Laboratories Del Dr. Esteve, S.A. | Salts of memantine and cox-inhibitors and their crystal form in the treatment of pain |
| CN103619817A (en) * | 2011-04-28 | 2014-03-05 | 百时美施贵宝公司 | Novel bicyclic nitrogen containing heteroaryl TGR5 receptor modulators |
| CN104237407A (en) * | 2014-09-12 | 2014-12-24 | 山东省医药工业研究所 | Method for detecting releasing rate of amantadine hydrochloride sustained release tablets |
| WO2016140952A1 (en) * | 2015-03-02 | 2016-09-09 | Taaneh, Inc. | Authenticated systems employing fluorescent diamond particles |
| US20190169179A1 (en) * | 2016-07-07 | 2019-06-06 | Ironwood Pharmaceuticals, Inc. | Solid forms of an sgc stimulator |
| CN108218844A (en) * | 2018-03-08 | 2018-06-29 | 合肥科大生物技术有限公司 | A kind of Memantine Paxil eutectic salts and preparation method thereof, pharmaceutical composition, application |
| US20210038590A1 (en) * | 2018-03-08 | 2021-02-11 | Hefei Keda Bio-Technology Co. Ltd | Memantine paroxetine cocrystal salt and its preparation method, pharmaceutical composition and application |
| CN109632702A (en) * | 2019-01-22 | 2019-04-16 | 天津中医药大学 | A kind of detection method of honeysuckle content |
| CN110845339A (en) * | 2019-11-08 | 2020-02-28 | 湖南洞庭药业股份有限公司 | Synthetic method of memantine hydrochloride |
| CN112730652A (en) * | 2020-12-17 | 2021-04-30 | 植恩生物技术股份有限公司 | Memantine hydrochloride and detection method of impurities thereof |
Non-Patent Citations (1)
| Title |
|---|
| 高秀蕊等: "《仪器分析操作技术》", 中国石油大学出版社 * |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Xie et al. | Selective detection of chloramphenicol in milk based on a molecularly imprinted polymer–surface‐enhanced Raman spectroscopic nanosensor | |
| CN109406474A (en) | A kind of aggregation-induced emission-molecular engram fluorescent optical sensor preparation method and application detecting rhodamine B | |
| Agatonović-Kuštrin et al. | Spectrophotometric study of diclofenac-Fe (III) complex | |
| CN114199812A (en) | Method for detecting memantine hydrochloride in memantine hydrochloride sustained-release preparation | |
| CN110161165A (en) | It is a kind of while detecting the analysis method of polycyclic aromatic hydrocarbon and its Metabolism of hydroxyl content level in hair | |
| CN115267017B (en) | Method for detecting organic tin by combining dispersed solid phase extraction material and GC-MS | |
| CN100351628C (en) | Method of identifying true and false of propolis using liquid phase finger print atlas | |
| CN113075337A (en) | Method for detecting bisamide pesticides in water by liquid chromatography tandem mass spectrometry | |
| Harvey | Molecularly imprinted polymers for selective analysis of chemical warfare surrogate and nuclear signature compounds in complex matrices | |
| CN102250285B (en) | Semi-covalent molecularly imprinted polymer used for selectivity separating phenols, preparation method thereof, and application thereof | |
| CN105572249A (en) | Method for carrying out risk assessment on influence of activated carbon on wine product | |
| CN114965537A (en) | Method for measuring total chlorine and inorganic chlorine content in polycarbonate resin | |
| CN114594174B (en) | Detection method of impurity A in indapamide preparation | |
| CN110632238B (en) | Method for evaluating oxidation resistance of alkaloid in rice bran by TLC-CMS technology | |
| CN112067718B (en) | Establishment method of muskiness rheumatalgia-relieving plaster volatile component fingerprint, standard fingerprint and application thereof | |
| CN113945657A (en) | Chinese yam and counterfeit identification model thereof as well as construction method and application thereof | |
| CN1170135C (en) | Method for enriching and detecting aminomercury chloride in cosmetics | |
| EP3446099A1 (en) | Method for sequencing oligosaccharides | |
| CN106198829B (en) | A kind of method of fire retardant and content of plasticizing agent in Rapid Simultaneous Determination electronic product | |
| CN112964822A (en) | Analysis and separation method of related substance L-2-aminobutyric acid in D-2-aminobutanol | |
| CN108948295A (en) | A kind of preparation method with the Raman active substrate to malachite green suction-operated | |
| CN108490085A (en) | A kind of quick " fingerprint " discriminating detection method for distinguishing lignite | |
| CN113917036B (en) | Detection method of deer flower bacteriocin | |
| CN113433255B (en) | Method for judging extraction settling performance of needle coke pretreatment unit settling extraction solvent | |
| CN113984947B (en) | Specific peptide fragment and method for determining antigen protein content in 9-valent HPV vaccine |
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: 226009 No. 1, Guangxing Road, comprehensive free trade zone, economic and Technological Development Zone, Nantong City, Jiangsu Province Applicant after: Nantong Lianya Pharmaceutical Co.,Ltd. Address before: 226009 No. 1, Guangxing Road, comprehensive free trade zone, economic and Technological Development Zone, Nantong City, Jiangsu Province Applicant before: NOVAST LABORATORIES (CHINA) Ltd. |
|
| CB02 | Change of applicant information |