CN113514561A - Detection method of lacosamide intermediate isomer - Google Patents
Detection method of lacosamide intermediate isomer Download PDFInfo
- Publication number
- CN113514561A CN113514561A CN202010277411.0A CN202010277411A CN113514561A CN 113514561 A CN113514561 A CN 113514561A CN 202010277411 A CN202010277411 A CN 202010277411A CN 113514561 A CN113514561 A CN 113514561A
- Authority
- CN
- China
- Prior art keywords
- lacosamide
- detection method
- mobile phase
- lacosamide intermediate
- isomer
- 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
- VPPJLAIAVCUEMN-GFCCVEGCSA-N lacosamide Chemical compound COC[C@@H](NC(C)=O)C(=O)NCC1=CC=CC=C1 VPPJLAIAVCUEMN-GFCCVEGCSA-N 0.000 title claims abstract description 55
- 229960002623 lacosamide Drugs 0.000 title claims abstract description 54
- 238000001514 detection method Methods 0.000 title claims abstract description 22
- 230000003287 optical effect Effects 0.000 claims abstract description 26
- 238000000034 method Methods 0.000 claims abstract description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract description 3
- 239000000945 filler Substances 0.000 claims abstract description 3
- 150000004676 glycans Chemical class 0.000 claims abstract description 3
- 229920001282 polysaccharide Polymers 0.000 claims abstract description 3
- 239000005017 polysaccharide Substances 0.000 claims abstract description 3
- 239000000741 silica gel Substances 0.000 claims abstract description 3
- 229910002027 silica gel Inorganic materials 0.000 claims abstract description 3
- 238000004305 normal phase HPLC Methods 0.000 claims abstract 2
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 12
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 12
- 239000000523 sample Substances 0.000 claims description 9
- 239000012488 sample solution Substances 0.000 claims description 7
- 238000000926 separation method Methods 0.000 claims description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- 239000007788 liquid Substances 0.000 claims description 6
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 4
- 235000019441 ethanol Nutrition 0.000 claims description 4
- 239000011259 mixed solution Substances 0.000 claims description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 2
- 239000000654 additive Substances 0.000 abstract 1
- 230000000996 additive effect Effects 0.000 abstract 1
- 230000035945 sensitivity Effects 0.000 abstract 1
- 239000000543 intermediate Substances 0.000 description 39
- 238000004128 high performance liquid chromatography Methods 0.000 description 8
- 230000014759 maintenance of location Effects 0.000 description 7
- 101000655609 Streptomyces azureus Thiostrepton Proteins 0.000 description 5
- 108010052164 Sodium Channels Proteins 0.000 description 4
- 102000018674 Sodium Channels Human genes 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 4
- HQMLIDZJXVVKCW-REOHCLBHSA-N L-alaninamide Chemical compound C[C@H](N)C(N)=O HQMLIDZJXVVKCW-REOHCLBHSA-N 0.000 description 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 230000002779 inactivation Effects 0.000 description 3
- 238000010829 isocratic elution Methods 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- UNEJKIYFRJYDAK-UHFFFAOYSA-N ethanol;n-ethylethanamine;propan-2-ol Chemical compound CCO.CC(C)O.CCNCC UNEJKIYFRJYDAK-UHFFFAOYSA-N 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- 239000000243 solution Substances 0.000 description 2
- 108091006146 Channels Proteins 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 102000013008 Semaphorin-3A Human genes 0.000 description 1
- 108010090319 Semaphorin-3A Proteins 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 229960003965 antiepileptics Drugs 0.000 description 1
- 238000007872 degassing Methods 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000001037 epileptic effect Effects 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- QKGYJVXSKCDGOK-UHFFFAOYSA-N hexane;propan-2-ol Chemical compound CC(C)O.CCCCCC QKGYJVXSKCDGOK-UHFFFAOYSA-N 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 208000004296 neuralgia Diseases 0.000 description 1
- 208000021722 neuropathic pain Diseases 0.000 description 1
- 238000005220 pharmaceutical analysis Methods 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 238000011002 quantification Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 239000012085 test solution Substances 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 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
- G01N30/26—Conditioning of the fluid carrier; Flow patterns
- G01N30/28—Control of physical parameters of the fluid carrier
- G01N30/34—Control of physical parameters of the fluid carrier of fluid composition, e.g. gradient
-
- 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
- G01N30/62—Detectors specially adapted therefor
- G01N30/74—Optical detectors
-
- 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
- G01N30/8624—Detection of slopes or peaks; baseline correction
- G01N30/8631—Peaks
- G01N30/8637—Peak shape
-
- 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
- G01N30/88—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86
-
- 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
- G01N30/88—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86
- G01N2030/8809—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 analysis specially adapted for the sample
- G01N2030/884—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 analysis specially adapted for the sample organic compounds
-
- 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
- G01N30/88—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86
- G01N2030/8809—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 analysis specially adapted for the sample
- G01N2030/8877—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 analysis specially adapted for the sample optical isomers
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)
- Spectroscopy & Molecular Physics (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
The present invention belongs to the field of analytical chemistry. The invention discloses a detection method of lacosamide intermediate isomer, which comprises the following steps: adopting normal phase high performance liquid chromatography, taking silica gel coated with polysaccharide derivatives as chromatographic column filler, taking n-hexane-lower alcohol-alkaline additive as mobile phase, quantitatively determining the content of lacosamide intermediate optical isomer, and indicating the stability of lacosamide intermediate optical isomer. The method has the advantages of strong specificity, high sensitivity and accuracy and simple and convenient operation.
Description
Technical Field
The invention belongs to the technical field of pharmaceutical analysis, and particularly relates to a detection method of lacosamide intermediate isomers.
Background
Lacosamide (Lacosamide) is an antiepileptic drug that targets sodium channels as a therapeutic target for pain, and modulates sodium ion channels in a novel manner: the slow inactivation sodium channel is selectively enhanced without having effect on the fast inactivation channel, and the sodium channel inactivation can be selectively promoted, and the collapsin response regulator protein-2 (CRMP-2) can be regulated, so that the epileptic degree can be effectively relieved, and the neuropathic pain possibly caused by diabetes can be relieved. (R) -amino-N-benzyl-3-methoxy alaninamide dihydrogen phosphate is an important intermediate for synthesizing lacosamide, and has the following structure:
the chiral isomer is (S) -amino-N-benzyl-3-methoxy alanyl amide dihydric phosphate, and the structure is as follows:
the content of chiral isomers in (R) -amino-N-benzyl-3-methoxy alaninamide dihydrogen phosphate is effectively controlled, the amount of lacosamide chiral isomers can be reduced, and the difficulty and the work of chiral resolution are reduced. Therefore, the determination of the chiral isomer of the (R) -amino-N-benzyl-3-methoxy alaninamide dihydrogen phosphate salt has important influence on the subsequent reaction and the quality control of lacosamide.
Disclosure of Invention
The invention aims to provide a liquid chromatography separation detection method for lacosamide intermediate (R) -amino-N-benzyl-3-methoxy alaninamide dihydrogen phosphate and chiral isomers thereof. The method can accurately detect the content of (R) -amino-N-benzyl-3-methoxy alaninamide dihydrogen phosphate isomer, and is favorable for ensuring the quality of lacosamide bulk drugs and preparations.
The invention relates to a detection method of lacosamide intermediate isomers, which comprises the steps of taking silica gel coated with polysaccharide derivatives on the surface as a chromatographic column filler, taking n-hexane-lower alcohol-diethylamine as a mobile phase, and analyzing and detecting lacosamide intermediates and lacosamide isomers, wherein the proportion of the mobile phase is 65:35: 0-95: 5: 0.15.
The lower alcohol in the mobile phase is selected from one or more of methanol, absolute ethyl alcohol, isopropanol, propanol and butanol, the lower alcohol is preferably absolute ethyl alcohol or a mixed solution of absolute ethyl alcohol and isopropanol, and the volume ratio of the absolute ethyl alcohol to the isopropanol in the mixed solution is 2: 1-6: 1.
The chiral chromatographic column adopted by the invention is CHIRALPAK AS-H.
The detection method can be realized according to the following method:
(1) taking a proper amount of lacosamide intermediate, dissolving a sample by using a mobile phase, and preparing a sample solution containing about 0.1-0.2 mg of lacosamide intermediate per 1 mL;
(2) setting the flow velocity of a mobile phase to be 0.5-1.5 mL/min, the detection wavelength to be 205-254 nm, and the column temperature: 20-40 ℃;
(3) and (3) injecting 10-50 mu L of the sample solution in the step (1) into a liquid chromatograph to complete the separation and determination of the lacosamide intermediate and the optical isomer thereof.
Wherein:
shimadzu high performance liquid chromatograph: an LC-20AB pump; an SPD-20A detector; SIL-20A autosampler;
a CTO-10ASVP column incubator; DGU-20A3Degassing machine
A chromatographic column: CHIRALPAK AS-H (250 mm 4.6 mm, 5 μm)
Mobile phase: n-hexane-anhydrous ethanol-isopropanol-diethylamine
Flow rate: 1.0mL/min
Detection wavelength: 215nm
Column temperature: 30 deg.C
Sample introduction volume: 20 μ L
According to the invention, a chromatographic column CHIRALPAK AS-H (250 mm x 4.6 mm, 5 μm) is adopted, so that lacosamide intermediates and optical isomers can be effectively separated, and the optical purity of the lacosamide intermediates can be accurately measured; the method solves the problem of separation and analysis of lacosamide intermediates and optical isomers, ensures the purity of the lacosamide intermediates, and further ensures the quality of lacosamide to be controllable (the result is shown in the attached figures 1-5).
Drawings
FIG. 1 is a HPLC chart of lacosamide intermediate and optical isomers in example 1;
FIG. 2 is a HPLC chart of lacosamide intermediate and optical isomers in example 2;
FIG. 3 is a solvent HPLC plot at the time of example 3;
FIG. 4 is a HPLC chart of lacosamide intermediate and optical isomers in example 3;
FIG. 5 is a HPLC chart of lacosamide intermediate in example 3.
The specific implementation mode is as follows:
the following examples are presented to further understand the present invention, but are not intended to limit the scope of the practice. The lacosamide intermediate and the isomer detection method thereof according to the present invention will be further described in detail by way of the following examples, but it should not be construed that the scope of the above-described subject matter of the present invention is limited to the following examples, and all the technologies realized based on the above-described contents of the present invention fall within the scope of the present invention.
Example 1
Apparatus and conditions
Shimadzu high performance liquid chromatograph: LC-20AB pump, SPD-20A detector, SIL-20A automatic sample introduction, CTO-10ASvp column incubator, LCsolution workstation, DGU-20A3A degasser;
a chromatographic column: chiralpak AS-H column (4.6 x 250mm, 5 μm);
mobile phase: n-hexane-isopropanol (75: 25), isocratic elution;
flow rate: 1.0 ml/min;
detection wavelength: 215 nm;
sample introduction volume: 20 mu l of the mixture;
column temperature: at 30 ℃.
Experimental procedure
Dissolving appropriate amount of lacosamide intermediate and optical isomer in mobile phase to obtain sample solution containing lacosamide intermediate and optical isomer about 0.2 mg/mL. Performing high performance liquid chromatography analysis according to the conditions, and recording a chromatogram. The result is shown in figure 1, under the chromatographic conditions, the chromatographic peak with the retention time of 16.535min in figure 1 is the chromatographic peak of the lacosamide intermediate, and the chromatographic peak with the retention time of 21.981min is the optical isomer of the lacosamide intermediate. Under the condition, the lacosamide intermediate is completely separated from the optical isomer thereof, but the peak shape is poor.
Example 2
Apparatus and conditions
Shimadzu high performance liquid chromatograph: LC-20AB pump, SPD-20A detector, SIL-20A automatic sample introduction, CTO-10ASvp column incubator, LCsolution workstation, DGU-20A3A degasser;
a chromatographic column: chiralpak AS-H column (4.6 x 250mm, 5 μm);
mobile phase: n-hexane-absolute ethyl alcohol-diethylamine (80: 20: 0.1), isocratic elution;
flow rate: 1.0 ml/min;
detection wavelength: 215 nm;
sample introduction volume: 20 mu l of the mixture;
column temperature: at 30 ℃.
Experimental procedure
Dissolving appropriate amount of lacosamide intermediate and optical isomer in mobile phase to obtain sample solution containing lacosamide intermediate and optical isomer about 0.2 mg/mL. Performing high performance liquid chromatography analysis according to the conditions, and recording a chromatogram. The result is shown in figure 2, under the chromatographic conditions, the chromatographic peak with the retention time of 9.165min in figure 2 is the chromatographic peak of the lacosamide intermediate, and the chromatographic peak with the retention time of 10.217min is the optical isomer of the lacosamide intermediate. Under the condition, the peak shape of each color spectrum is good, and the lacosamide intermediate and the optical isomer thereof are completely separated.
Example 3
Apparatus and conditions
Shimadzu high performance liquid chromatograph: LC-20AB pump, SPD-20A detector, SIL-20A automatic sample introduction, CTO-10ASvp column incubator, LCsolution workstation, DGU-20A3A degasser;
a chromatographic column: chiralpak AS-H column (4.6X 250mm, 5 μm)
Mobile phase: n-hexane-dehydrated ethanol-isopropanol-diethylamine (80: 16:4: 0.05), isocratic elution
Flow rate: 1.0 ml/min;
detection wavelength: 215 nm;
sample introduction volume: 20 mu l of the mixture;
column temperature: at 30 ℃.
Experimental procedure
Dissolving appropriate amount of lacosamide intermediate and optical isomer in mobile phase to obtain sample solution containing lacosamide intermediate and optical isomer about 0.2 mg/mL. Performing high performance liquid chromatography analysis according to the conditions, and recording a chromatogram. The result is shown in attached figures 3-5, under the chromatographic conditions, figure 3 is a solvent chromatogram, the chromatographic peak with retention time of 12.554min in figure 4 is the chromatographic peak of the lacosamide intermediate, and the chromatographic peak with retention time of 14.308min is the optical isomer of the lacosamide intermediate. The chromatographic peak with retention time of 12.516min in fig. 5 is the chromatographic peak of lacosamide intermediate. As can be seen from the figure, the lacosamide intermediate and the optical isomer thereof have good peak shapes under the condition and meet the separation requirement.
Specificity test
Taking a proper amount of lacosamide intermediate and optical isomer, respectively dissolving the samples by using mobile phases, and preparing a solution containing about 0.2mg/mL of lacosamide intermediate and optical isomer as a test solution. The separation measurement was carried out under the chromatographic conditions of example 3, and the chromatogram was recorded. As can be seen from fig. 3 to 5, under the condition, the chromatographic peak shapes of the lacosamide intermediate and the optical isomer are good, the separation degree meets the requirement, and the solvent does not interfere with the measurement of the lacosamide intermediate and the optical isomer.
Detection limit and quantification limit
The lacosamide intermediate and isomer solution is diluted step by step, the concentration corresponding to the main peak response value (peak height) of 10 of the baseline noise is a quantitative limit, the concentration corresponding to the main peak response value (peak height) of 3 of the baseline noise is a detection limit, and the results are shown in the following table:
Claims (6)
1. a detection method of lacosamide intermediate isomer is characterized in that: by adopting normal-phase high performance liquid chromatography, silica gel coated with polysaccharide derivatives on the surface is used as a chromatographic column filler, n-hexane-lower alcohol-diethylamine is used as a mobile phase, the proportion of the mobile phase is 65:35: 0-95: 5:0.15, and the detected lacosamide intermediate isomers mainly comprise:
。
2. the detection method according to claim 1, wherein the chromatographic column is preferably CHIRALPAK AS-H.
3. The detection method according to claim 1, wherein the lower alcohol is one or more selected from the group consisting of: methanol, absolute ethanol, isopropanol, propanol and butanol.
4. The detection method according to claim 3, wherein the lower alcohol is preferably absolute ethyl alcohol or a mixed solution of absolute ethyl alcohol and isopropanol, and the volume ratio of the absolute ethyl alcohol to the isopropanol in the mixed solution is 2: 1-6: 1.
5. The detection method according to claim 1, comprising the steps of:
(1) taking a proper amount of lacosamide intermediate, dissolving a sample by using a mobile phase, and preparing a sample solution containing about 0.1-0.2 mg of lacosamide intermediate per 1 mL;
(2) setting the flow velocity of a mobile phase to be 0.5-1.5 mL/min, the detection wavelength to be 205-254 nm, and the column temperature: 20-40 ℃;
(3) and (3) injecting 10-50 mu L of the sample solution in the step (1) into a liquid chromatograph to complete the separation and determination of the lacosamide intermediate and the optical isomer.
6. The method according to claim 5, wherein said detection wavelength in step (2) is preferably 215nm, the flow rate is preferably 1.0mL/min, and the column box temperature is preferably 30 ℃.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010277411.0A CN113514561A (en) | 2020-04-10 | 2020-04-10 | Detection method of lacosamide intermediate isomer |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202010277411.0A CN113514561A (en) | 2020-04-10 | 2020-04-10 | Detection method of lacosamide intermediate isomer |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN113514561A true CN113514561A (en) | 2021-10-19 |
Family
ID=78060535
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202010277411.0A Pending CN113514561A (en) | 2020-04-10 | 2020-04-10 | Detection method of lacosamide intermediate isomer |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN113514561A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114527205A (en) * | 2022-01-21 | 2022-05-24 | 石家庄四药有限公司 | Method for detecting isomer of 2-tert-butyloxycarbonylamino-N-benzyl-3-methoxypropionamide |
| CN115825300A (en) * | 2022-11-30 | 2023-03-21 | 山东百诺医药股份有限公司 | Reverse phase liquid chromatography method for detecting lacosamide enantiomer |
-
2020
- 2020-04-10 CN CN202010277411.0A patent/CN113514561A/en active Pending
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114527205A (en) * | 2022-01-21 | 2022-05-24 | 石家庄四药有限公司 | Method for detecting isomer of 2-tert-butyloxycarbonylamino-N-benzyl-3-methoxypropionamide |
| CN115825300A (en) * | 2022-11-30 | 2023-03-21 | 山东百诺医药股份有限公司 | Reverse phase liquid chromatography method for detecting lacosamide enantiomer |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN113514561A (en) | Detection method of lacosamide intermediate isomer | |
| CN107941970B (en) | Separation and detection method of D-p-hydroxyphenylglycine and enantiomer thereof | |
| CN110849980A (en) | Method for detecting content of enantiomer in isopropyl L-alanine | |
| Urvaka et al. | Rapid separation of all four tocopherol homologues in selected fruit seeds via supercritical fluid chromatography using a solid-core C18 column | |
| CN107843656B (en) | Detection method of 2, 4-dimethylthiophenol related substances | |
| CN116482268A (en) | Method for detecting impurities in argatroban raw material or preparation | |
| CN110836930A (en) | Method for measuring content of dichlorobutane in levetiracetam by gas chromatography-mass spectrometry | |
| CN115112784A (en) | Method for detecting enantiomer in tolterodine tartrate | |
| CN112630314B (en) | Separation method of L-alanine isopropyl ester hydrochloride and enantiomer thereof | |
| CN112881538B (en) | Method for detecting impurities and enantiomers in fudosteine and fudosteine tablets | |
| CN113075302A (en) | High performance liquid chromatography for separating and determining optical isomer of brivaracetam | |
| CN114660183A (en) | High performance liquid chromatography analysis method for separating and measuring L-alanine isopropyl ester hydrochloride enantiomer | |
| CN113358790A (en) | Method for detecting related substances in nicergoline and preparation thereof | |
| CN112540131A (en) | High performance liquid chromatography for separating and determining lacosamide intermediate optical isomer | |
| CN113514560A (en) | Detection method of levomilnacipran hydrochloride and isomer thereof | |
| CN106442793B (en) | A kind of detection method of the intermediate for preparing Afatinib and its enantiomter | |
| CN111257441B (en) | Method for detecting impurities in parecoxib sodium synthesis process | |
| CN111220716A (en) | Method for measuring optical purity of levetiracetam intermediate | |
| CN110873763A (en) | Method for separating and measuring optical isomers of starting material of brivaracetam by gas chromatography | |
| Bousquet et al. | Determination of valproic acid salts in pharmaceutical preparations by high performance liquid chromatography with coulometric electrochemical detection | |
| CN116879428B (en) | High performance liquid analysis method for residual content of phosphorylcholine in L-alpha-phosphorylcholine | |
| CN116539765B (en) | Method for detecting related substances of teprenone capsules | |
| CN115015445A (en) | Detection and analysis method of L-alanine isopropyl ester hydrochloride and isomer thereof | |
| CN115656380A (en) | HPLC-UV detection method of MTV enantiomer | |
| CN117330668A (en) | Method for separating and measuring isomer in (S) -2-methoxy-1-propanol |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Application publication date: 20211019 |
|
| WD01 | Invention patent application deemed withdrawn after publication |