1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid 2-methoxyethyl 1-methylethyl ester
nimodipine
CAS: 66085-59-4
Molecular Formula: C21H26N2O7
1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid 2-methoxyethyl 1-methylethyl ester - Names and Identifiers
1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid 2-methoxyethyl 1-methylethyl ester - Physico-chemical Properties
| Molecular Formula | C21H26N2O7 |
| Molar Mass | 418.44 |
| Density | 1.3268 (rough estimate) |
| Melting Point | 125°C |
| Boling Point | 536.21°C (rough estimate) |
| Flash Point | 272.1°C |
| Solubility | Soluble in ethanol or acetone, insoluble in water. |
| Vapor Presure | 3.63E-11mmHg at 25°C |
| Appearance | Pale yellow crystalline powder |
| Color | white |
| Merck | 14,6551 |
| pKa | 2.77±0.70(Predicted) |
| Storage Condition | 2-8°C |
| Stability | Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months. |
| Refractive Index | 1.6500 (estimate) |
| MDL | MFCD00153848 |
| Physical and Chemical Properties | Melting Point: 125°C |
| Use | Calcium channel blockers, mainly used for the treatment of ischemic cerebrovascular disease, migraine |
1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid 2-methoxyethyl 1-methylethyl ester - Risk and Safety
| Hazard Symbols | Xn - Harmful |
| Risk Codes | R20/21/22 - Harmful by inhalation, in contact with skin and if swallowed. R48/22 - Harmful danger of serious damage to health by prolonged exposure if swallowed. |
| Safety Description | 36 - Wear suitable protective clothing. |
| WGK Germany | 1 |
| RTECS | US7975500 |
| HS Code | 29333990 |
| Hazard Class | IRRITANT |
| Toxicity | LD50 in mice, rats (mg/kg): 3562, 6599 orally; 33, 16 i.v. (Schlüter) |
1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid 2-methoxyethyl 1-methylethyl ester - Reference
| Reference Show more | 1. Wang Shengxin, Yan Xiangli, Zheng haowan, Wang Lisheng. Effects of calycosin and paeoniflorin on PI3K/AKT signaling pathway in oxygen-glucose deprivation-reperfusion HT22 cells [J]. Chinese new medicines and clinical pharmacology, 2020,31(02):138-142. 2. Yuan Lingyue, zidongyu. Correlation between inflammatory response induced by ketamine and NF-κB signaling pathway in mice with cerebral ischemia reperfusion injury [J]. China pharmacist, 2020,23(04):614-619. 3. Zhang Juanhong, Wang Chang, Zhao Anpeng, etc. Interaction between amoxicillin and nifedipine mediated by intestinal flora [J]. Chinese Journal of Pharmacy, 2018, 053(010):1721-1725. 4. Determination of LC-MS of 25 characteristic components in danhe granules and analysis of consistency of preparations [J]. Chinese herbal medicine 2019 v.50;No.659(24):63-72. 5. Zhu Huiyuan, Miao Qi, Wang Jiang, Liu Yanru, Wang Wenyan, Luo Bin, Fang Shan. Effect of effective components of Salvia miltiorrhiza and safflower on inflammatory factors in brain tissue of rats with ischemic stroke [J]. Chinese Journal of Experimental prescriptions, 2020,26(21):77-83. 6. Bi Y, Lv B, Li L, Lee RJ, Xie J, Qiu Z, Deng L. A Liposomal Formulation for Improving Solubility and Oral Bioavailability of nifedipin. Molecules. 2020; 25(2):338. https://doi.org/10.3390/molecules25020338 7. [IF=6.419] Juanhong Zhang et al."Plateau hypoxia attenuates the metabolic activity of intestinal flora to enhance the bioavailability of nifedipine."Drug Deliv. 2018;25(1):1175-1181 8. [IF=4.411] Ye Bi et al."A Liposomal Formulation for Improving Solubility and Oral Bioavailability of Nifedipine."Molecules. 2020 Jan;25(2):338 9. [IF=3.996] Wang Wen-Jun et al."Oxymatrine Alleviates Hyperglycemic Cerebral Ischemia/Reperfusion Injury via Protecting Microvessel."Neurochem Res. 2022 Jan;:1-14 10. [IF=4.162] Yingying He et al."Identification of Active Ingredients of Huangqi Guizhi Wuwu Decoction for Promoting Nerve Function Recovery After Ischemic Stroke Using HT22 Live-Cell-Based Affinity Chromatography Combined with HPLC-MS/MS."Drug Des Dev Ther. 2021; 15: |
1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid 2-methoxyethyl 1-methylethyl ester - Nature
Open Data Verified Data
yellow crystalline powder, odorless and tasteless. Soluble in ethanol or acetone, insoluble in water. The melting point was 124-128 °c.
Last Update：2024-01-02 23:10:35
1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid 2-methoxyethyl 1-methylethyl ester - Preparation Method
Open Data Verified Data
The condensation of M-nitrobenzaldehyde and methyloxyethyl acetoacetate catalyzed by hydrochloric acid or concentrated sulfuric acid, and the obtained product is then cyclized with isopropyl 3-aminobutenoate in anhydrous ethanol under heating, nimodipine may be obtained. Alternatively, M-nitrobenzaldehyde and isopropyl acetoacetate are dissolved by stirring at room temperature, glacial acetic acid and piperidine are added, stirred and solidified, and left to stand for heat preservation, and then ethanol is added and heated to reflux until the solid is dissolved. The crystals were precipitated by filtration and dried to obtain isopropyl 2-(3-nitrobenzylidene) acetoacetate, which reacted with 2-methoxyethyl 3-aminobutenoate, and the crude product was recrystallized with ethanol, nimodipine.
Last Update：2022-01-01 09:10:21
1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid 2-methoxyethyl 1-methylethyl ester - Standard
Authoritative Data Verified Data
This product is 2, 6-dimethyl-4-(3-nitrophenyl)-1, 4-dihydro-3, 5-pyridinedicarboxylic acid 2-methoxyethyl isopropyl ester. The content of C21H26N207 shall be 98.5% ~ 101.5% calculated as dry product.
Last Update：2024-01-02 23:10:35
1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid 2-methoxyethyl 1-methylethyl ester - Trait
Authoritative Data Verified Data
- This product is light yellow crystalline powder or powder; Odorless. Unstable in light.
- This product is soluble in acetone, chloroform or ethyl acetate, soluble in ethanol, slightly soluble in ether, almost insoluble in water.
melting point
The melting point of this product (General 0612) is 124~128°C.
Last Update：2022-01-01 11:42:31
1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid 2-methoxyethyl 1-methylethyl ester - Use
Open Data Verified Data
developed by Bayer, Germany. Calcium channel antagonists, with anti-ischemic and anti-vasoconstrictor effects. For the expansion of cerebral blood vessels and brain function improvement drugs. Mainly used for cerebrovascular diseases, such as cerebral vascular perfusion, cerebral vasospasm, stroke and migraine.
Last Update：2022-01-01 09:10:21
1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid 2-methoxyethyl 1-methylethyl ester - Differential diagnosis
Authoritative Data Verified Data
- take about 20mg of this product, add 2ml of ethanol, add 2ml of new 5% ferrous ammonium sulfate solution, 1 drop of 1.5mol/L sulfuric acid solution and 1ml of 0.5mol/L potassium hydroxide solution, with strong shaking, the precipitate changed from gray-green to red-brown within 1 min.
- take an appropriate amount of this product and add ethanol to make a solution containing 10ug per 1 ml. According to ultraviolet-visible spectrophotometry (General 0401), there is a maximum absorption at a wavelength of 237nm.
- The infrared absorption spectrum of this product is consistent with that of the control (Spectrum set 599).
Last Update：2022-01-01 11:42:31
1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid 2-methoxyethyl 1-methylethyl ester - Safety
Open Data Verified Data
LD50 mice, rats (mg/kg):3562, 6599 orally; 33. 16 I. V.
Last Update：2022-01-01 09:10:21
1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid 2-methoxyethyl 1-methylethyl ester - Exam
Authoritative Data Verified Data
optical rotation
take this product, add acetone to dissolve and quantitatively dilute to make a solution containing 50mg per lml, and determine it according to law (General rule 0621). The optical rotation is 0.10 ° to +0.10 °.
Related substances
operation in the dark. Take this product, precision weighing, add mobile phase dissolution and quantitative dilution to make a solution containing about 0.2mg per 1ml, as a test solution; Another 2, 6-dimethyl-4-(3-nitrophenyl)-3, 5-pyridinedicarboxylic acid 2-methoxyethyl isopropyl ester (impurity I) reference, precision weighing, dissolve and quantitatively dilute with mobile phase to make a solution containing about 20ug per 1ml. Take 1ml with precision and put it in a 100ml measuring flask, as a control solution. Test according to high performance liquid chromatography (General 0512). Silica gel bonded with eighteen alkyl silane was used as the filler; Methanol-acetonitrile + water (35:38:27) was used as the mobile phase; The detection wavelength was 235nm. Take appropriate amount of nimodipine reference substance and impurity I reference substance, add mobile phase to dissolve and dilute to make a mixed solution containing about 200ug and 1ug in each lml, take 20 u1, and inject human liquid chromatograph, the degree of separation of the nimodipine peak from the impurity I peak should be greater than 3.0. 20 u1 of the test solution and the control solution were respectively injected into the human liquid chromatograph, and the chromatogram was recorded to 3 times of the retention time of the main component peak. If there are chromatographic peaks in the chromatogram of the test solution that are consistent with the retention time of impurity I peak, the peak area shall be calculated according to the external standard method, and shall not exceed 0.1%; other single impurity peak area shall not be greater than 0.5 times (0.5%) of nimodipine peak area in the control solution, each impurity peak area (impurity I Peak area multiplied by 1.78) the sum should not be greater than the area of the nimodipine peak in the control solution (1.0%). The chromatogram of the test solution is 0.02 times smaller than the main peak area of the control solution.
loss on drying
take this product, dry to constant weight at 105°C, weight loss shall not exceed 0.5% (General rule 0831).
ignition residue
take l.Og of this product and check it according to law (General rule 0841). The residue left shall not exceed 0.1%.
Heavy metals
The residue left under the item of taking the ignition residue shall not contain more than 10 parts per million of heavy metal when examined by law (General Principles 0821, Law II).
Last Update：2022-01-01 11:42:32
1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid 2-methoxyethyl 1-methylethyl ester - Content determination
Authoritative Data Verified Data
take this product about 0.18g, precision weighing, add anhydrous ethanol 25ml, slightly warm to dissolve, add perchloric acid solution (take 70% of 8.5 perchloric acid solution, add water to 100ml)25ml, add 4 drops of O-Phenanthroline indicator solution, with cerium sulfate titration solution (0.1 mol/L) titration to the solution changed from orange-red to light yellow-green, and the titration results were corrected with a blank test. Each 1 ml of cerium sulfate titration solution (0.1 mol/L) corresponds to 20.92mg of C21H26N2O7.
Last Update：2022-01-01 11:42:33
1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid 2-methoxyethyl 1-methylethyl ester - Category
Authoritative Data Verified Data
calcium channel blockers.
Last Update：2022-01-01 11:42:33
1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid 2-methoxyethyl 1-methylethyl ester - Storage
Authoritative Data Verified Data
light-shielded, sealed, and stored in a dry place.
Last Update：2022-01-01 11:42:33
1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid 2-methoxyethyl 1-methylethyl ester - Nimotop(Nimodipine Tablets)
Authoritative Data Verified Data
This product contains Nimodipine (C21H26N207) should be 90.0% to 110.0% of the label.
trait
This product is white-like to light yellow tablets, film-coated tablets or sugar-coated tablets; After removing the coating, it is white-like to light yellow.
identification
- take an appropriate amount of fine powder of this product (about 40mg of nimodipine), add 5ml of ethanol, shake to dissolve nimodipine, filter, and take about 3ml of filtrate, add 2ml of newly prepared 5% ammonium ferrous sulfate solution, add 1 drop of 1.5mol/L sulfuric acid solution and 1ml of 0.5mol/L potassium hydroxide solution, shake strongly, and change the precipitate from gray-green to red-brown within 1 minute.
- in the chromatogram recorded under the content determination item, the retention time of the main peak of the test solution should be consistent with the retention time of the main peak of the reference solution.
examination
- the related substances were protected from light. Take the appropriate amount of fine powder (about equivalent to 10 mg of nimodipine) under the content determination item, weigh it accurately, put it in a 50ml measuring flask, add the appropriate amount of mobile phase, sonicate for about 15 minutes to dissolve nimodipine, and let it cool, dilute to the scale with mobile phase, shake, centrifuge for 10 minutes (3000 rpm), take the supernatant as the test solution; Take the impurity I control, precision weighing, add the mobile phase to dissolve and quantitatively dilute to make a solution containing about 20ug per lml, take 5ml with precision, put it in a 100ml measuring flask, add 1ml of test solution with precision, dilute to the scale with mobile phase, as a control solution. According to the method of nimodipine related substances. If there are impurity peaks in the chromatogram of the test solution, the peak area shall be calculated according to the external standard method, except for the chromatographic peak whose relative retention time is less than 0.35 and the chromatographic peak whose retention time is consistent with that of impurity I, 0.5% of the labeled amount of nimodipine shall not be exceeded; The peak area of other individual impurities shall not be greater than that of nimodipine in the control solution (1.0%), and the peak area of each impurity (the peak area of impurity I times 1.78) the sum should not be greater than 2 times (2.0%) the area of the nimodipine peak in the control solution. The chromatogram of the test solution is 0.02 times smaller than the main peak area of the control solution.
- Content uniformity (20mg specification) protected from light. Take 1 tablet of this product, put it in mortar, grind it finely, add appropriate amount of mobile phase to grind it, and transfer it to 100ml measuring flask in fractions with mobile phase, according to the method under the content determination item, from the time of "ultrasonic about 15 minutes to dissolve nididipine", the content shall be determined according to law, and shall comply with the regulations (General rule 0941).
- dissolution rate protected from light. Take this product, according to the dissolution and release determination method (General 0931 second method), with acetate buffer solution (take sodium acetate 0.299g, add water 50ml, shake to dissolve, add glacial acetic acid 0.174g, dilute to 4.5 ml with water and shake well to obtain pH 0.3% (containing sodium dodecyl sulfate) ml as dissolution medium, rotate at 75 rpm, take 10ml of continuous filtrate accurately, put it in a 20ml(20mg specification) or 25ml(30mg specification) measuring flask, dilute to the scale with dissolution medium, shake well, and use it as a test solution; another 10 mg of nimodipine reference product was added into a 100ml measuring flask, and 10ml ethanol was added. The solution was dissolved by shaking, in a 50ml measuring flask, add the dissolution medium to dilute to the scale, shake, as a reference solution. The test solution and the reference solution were taken respectively, and the absorbance was measured at the wavelength of 238nm according to the ultraviolet-visible spectrophotometry (General rule 0401), and the dissolution amount of each tablet was calculated. The limit is 85% of the labeled amount and shall be in accordance with the provisions.
- others shall be in accordance with the relevant provisions under the item of tablets (General rule 0101).
Content determination
- measured by high performance liquid chromatography (General 0512).
- chromatographic conditions and system suitability test using eighteen alkyl silane bonded silica gel as filler; Methanol-acetonitrile-water (35:38:27) as mobile phase; The detection wavelength was 235Nm. The number of theoretical plates shall not be less than 8000 calculated by nimodipine peak, and the degree of separation between nimodipine peak and adjacent impurity peaks shall meet the requirements.
- The assay was operated in the dark. Take 20 tablets of this product (sugar-coated tablets should be removed from the coating), Precision weighing, fine, precision weighing an appropriate amount (about equivalent to nimodipine 10 mg), put it in a 50ml measuring flask, and add an appropriate amount of mobile phase, ultrasound for about 15 minutes to dissolve nimodipine, cool, dilute to scale with mobile phase, shake well, centrifuge for 10 minutes (3000 rpm), precisely measure 5ml supernatant, put it in 50ml measuring flask, dilute to scale with mobile phase, shake well, take 10ul as test solution, inject human liquid chromatograph, record chromatogram; Take nimodipine reference substance, the mobile phase is added to dissolve and quantitatively dilute to make a solution containing about 20ug per 1 ml, and the same method is used to determine the peak area according to the external standard method.
category
Same as nimodipine.
specification
(l)20mg (2)30mg
storage
light shielding, sealed storage.
Last Update：2022-01-01 11:42:34
1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid 2-methoxyethyl 1-methylethyl ester - Nimodipine dispersible tablets
Authoritative Data Verified Data
This product contains Nimodipine (C21H26N207) should be 90.0% to 110.0% of the label.
trait
This product is from yellowish to yellowish.
identification
- take an appropriate amount of fine powder of this product (about 40mg of nimodipine), add 5ml of ethanol, shake to dissolve nimodipine, filter, and take about 3ml of filtrate, add 2ml of newly prepared 5% ammonium ferrous sulfate solution, add 1 drop of 1.5mol/L sulfuric acid solution and 1ml of 0.5mol/L potassium hydroxide solution, shake strongly, and change the precipitate from gray-green to red-brown within 1 minute.
- in the chromatogram recorded under the content determination item, the retention time of the main peak of the test solution should be consistent with the retention time of the main peak of the reference solution.
examination
- the related substances were protected from light. Take the appropriate amount of fine powder (about equivalent to nimodipine lOmg) under the content determination item, weigh it accurately, put it in a 50ml measuring flask, add the appropriate amount of mobile phase, sonicate for about 15 minutes to dissolve nimodipine, let it cool, dilute to the scale with mobile phase, shake, centrifuge for 10 minutes (3000 rpm), take the supernatant as the test solution; Take the impurity I control, precision weighing, add the mobile phase to dissolve and quantitatively dilute to make a solution containing about 20ug per lml, take 5ml with precision, put it in a 100ml measuring flask, add 1ml of human test solution with precision, dilute to the scale with mobile phase, as a control solution. According to the method of nimodipine related substances. If there are impurity peaks in the chromatogram of the test solution, the peak area shall be calculated according to the external standard method, except for the chromatographic peak whose relative retention time is less than 0.35 and the chromatographic peak whose retention time is consistent with that of impurity I, 0.5% of the labeled amount of nimodipine shall not be exceeded; The peak area of other individual impurities shall not be greater than that of nimodipine in the control solution (1.0% ), and the peak area of each impurity (the peak area of impurity I times 1.78) the sum should not be greater than 2 times (2.0%) the area of the nimodipine peak in the control solution. The chromatogram of the test solution is 0.02 times smaller than the main peak area of the control solution.
- Content uniformity protected from light. Take 1 tablet of this product, put it in mortar, grind it finely, add appropriate amount of mobile phase to grind it, and transfer it to 100ml measuring flask in fractions with mobile phase, according to the method under the content determination item, from "ultrasonic about 15 minutes to dissolve nimodipine", the content shall be determined according to law, and shall comply with the regulations (General rule 0941).
- dissolution rate protected from light. Take this product, according to the dissolution and release determination method (General 0931 second method), with acetate buffer solution (take sodium acetate 0.299g, add water 50ml, shake to dissolve, add glacial acetic acid 0.174g, dilute to 4.5 ml with water and shake well to obtain pH 0.3% (containing sodium dodecyl sulfate) ml as dissolution medium, rotate at 75 rpm, precisely take 5ml of continued filtrate, put it in a 10ml measuring flask, dilute to the scale with dissolution medium, shake well, and use it as a test solution; Take about 10mg of nimodipine reference substance, precisely weigh it, put it in a 100ml measuring flask, add 10ml of ethanol, shake to dissolve, dilute to the scale with dissolved medium, shake well, take 5ml accurately, put it in a 50ml measuring flask, the dissolution medium was added and diluted to the scale, and the solution was used as a control solution. Take the test solution and the reference solution, according to the UV-visible spectrophotometry (General rule 0401), at the wavelength of 238nm, respectively, the absorbance was measured, and the dissolution of each tablet was calculated, the limit is 85% of the labeled amount and shall be in accordance with the provisions.
- others shall be in accordance with the relevant provisions under the item of tablets (General rule 0101).
Content determination
- measured by high performance liquid chromatography (General 0512).
- chromatographic conditions and system suitability test using eighteen alkyl silane bonded silica gel as filler; Methanol-acetonitrile-water (35:38:27) as mobile phase; The detection wavelength was 235Nm. The number of theoretical plates shall not be less than 8000 calculated by nimodipine peak, and the degree of separation between nimodipine peak and adjacent impurity peaks shall meet the requirements.
- The assay was operated in the dark. Take 20 tablets of this product, accurately weigh, grind, accurately weigh an appropriate amount (about 10mg equivalent to nimodipine), put it in a 50ml measuring flask, add an appropriate amount of mobile phase, sonicate for about 15 minutes to dissolve nimodipine, cool, dilute to the scale with mobile phase, shake well, centrifuge for 10 minutes (3000 revolutions per minute), accurately measure the supernatant 5ml, put it in a 50ml measuring flask, dilute to the scale with mobile phase, shake well, as a test solution, take lOul for precision measurement, inject into liquid chromatograph, record chromatogram; Take nimodipine reference substance for precision weighing, A solution containing about 20ug per 1 ml was prepared by dissolving and quantitatively diluting with the mobile phase and determined by the same method. According to the external standard method to calculate the peak area, that is.
category
Same as nimodipine.
specification
20mg
storage
light shielding, sealed storage.
Last Update：2022-01-01 11:42:35
1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid 2-methoxyethyl 1-methylethyl ester - Nimodipine Soft Capsules
Authoritative Data Verified Data
This product is made by dissolving nimodipine with suitable excipients. This product contains Nimodipine (C21H26N207) should be 90.0% to 110.0% of the label.
trait
The content of this product is yellow or yellow-brown viscous liquid.
identification
- light-shielding operation. Take the contents of 20 capsules of this product, put it in a 100ml beaker, add 100ml of water, stir to precipitate nimodipine, filter. The precipitate was dried at 60°C for 2 hours, about 30mg was taken, 2ml of ethanol was added to dissolve, and 2ml of a new 5% ammonium ferrous sulfate solution was added, 1.5 mol/L sulfuric acid solution 1 drop and 0.5mol/L potassium hydroxide methanol solution 1 ml, strong shaking, 1 min precipitation from gray-green to red-brown.
- take the dry precipitate under identification (1) and dissolve it with ethanol to make a solution containing 10ug per 1 ml, and measure it by UV-Vis spectrophotometry (General 0401), there is a maximum absorption at wavelengths of 237nm and 355nm.
- in the chromatogram recorded under the content determination item, the retention time of the main peak of the test solution should be consistent with the retention time of the main peak of the reference solution.
examination
- the related substances were protected from light. Take an appropriate amount of content (about 10mg equivalent to nimodipine) under the difference of loading volume, weigh it accurately, put it in a 50ml measuring flask, add an appropriate amount of mobile phase, and sonicate it for about 15 minutes to dissolve nimodipine, cool, dilute to the scale with mobile phase, shake well, filter, and take the filtrate as the test solution; Take an appropriate amount of impurity I reference, and weigh it accurately, add the mobile phase to dissolve and quantitatively dilute to make a solution containing about 20ug per lml, take 5ml with precision, put it in a 100ml measuring flask, add lml of human test solution with precision, dilute to the scale with mobile phase, as a control solution. According to the chromatographic conditions under the content determination item, the resolution of nimodipine peak and impurity I peak should be greater than 3.0. Then, 20ul of the test solution and the control solution are respectively injected into the human liquid chromatograph, and the chromatogram is recorded to 3.5 times of the retention time of the main component chromatographic peak. If there are impurity peaks in the chromatogram of the test solution, the peak area shall be calculated according to the external standard method, except that the chromatographic peaks with relative retention time less than 0.37 are excluded, and if there are chromatographic peaks with retention time consistent with impurity I, the Peak area of other single impurities shall not exceed 0.5 of the labeled amount of nimodipine, and the peak area of each impurity (Peak area of impurity I multiplied by 1.78) shall not be greater than the peak area of nimodipine in the control solution (). The sum should not be greater than 2 times (2.0%) the area of the nimodipine peak in the control solution. The chromatogram of the test solution is 0.02 times smaller than the main peak area of the control solution.
- dissolution rate protected from light. Take this product, according to the dissolution and release determination method (General 0931 second method), with acetate buffer solution (take sodium acetate 0.299g, add water 50ml, shake to dissolve, add glacial acetic acid 0.174g, dilute to 4.5 ml with water and shake well to obtain pH 0.3% (containing sodium dodecyl sulfate) ml for dissolution, at 75 rpm, filter the solution, and take the filtrate as the test solution; Take an appropriate amount of nimodipine reference substance, weigh it precisely, dissolve and dilute it with mobile phase to make a solution containing about 20ug per 1 ml, as a control solution. According to the chromatographic conditions under the content determination item, 20 u1 of the test solution and the reference solution are accurately measured, and the human liquid chromatograph is injected respectively, and the chromatogram is recorded. According to the external standard method, the dissolution amount of each particle was calculated by the peak area. The limit is 80% of the labeled amount and shall be in accordance with the provisions.
- others should comply with the relevant provisions under the capsule (General 0103).
determination of content
- measured by high performance liquid chromatography (General 0512).
- chromatographic conditions and system suitability test using eighteen alkyl silane bonded silica as filler; Methanol-acetonitrile-water (35:38:27) as mobile phase; The detection wavelength was 235nm; the retention time of the nimodipine peak was approximately 7 minutes. The number of theoretical plates shall not be less than 8000 calculated by nimodipine peak, and the degree of separation between nimodipine peak and adjacent impurity peaks shall meet the requirements.
- The assay was operated in the dark. Take the contents under the difference of loading amount, mix evenly, weigh an appropriate amount (about 10mg equivalent to nimodipine), put it in a 50ml measuring flask, and add an appropriate amount of mobile phase, ultrasound for about 15 minutes to dissolve nimodipine, cool, dilute to degree with mobile phase, shake well, filter, Take 5ml filtrate accurately, put it in 50ml measuring flask, dilute to scale with mobile phase, shake well, as a test solution, take 20u1 injection of human liquid chromatograph with precise volume, record chromatogram; Take appropriate amount of nimodipine reference substance, precise weighing, A solution containing about 20ug per 1 ml was prepared by dissolving and quantitatively diluting with the mobile phase and determined by the same method. According to the external standard method to calculate the peak area, that is.
category
Same as nimodipine.
specification
20mg
storage
light shielding, sealed storage.
Last Update：2022-01-01 11:42:36
1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid 2-methoxyethyl 1-methylethyl ester - Nimotop (Nimodipine Injection)
Authoritative Data Verified Data
This product is a sterile aqueous solution of nimodipine. The content of Nimodipine (C21H26N207) shall be between 90.0% and 110.0% of the labeled amount.
trait
This product is an almost colorless clear liquid.
identification
- take an appropriate amount of this product (about 20mg equivalent to nimodipine), place it in a separatory funnel, add 30ml of ether for shaking extraction, let it stand, separate the ether layer, and let it stand on a water bath for evaporation, after cooling, the residue was added with 2ml of ethanol, stirred to dissolve, transferred to a test tube, and added with 3ml of 1% mercuric chloride solution, resulting in white precipitation.
- in the chromatogram recorded under the content determination item, the retention time of the main peak of the test solution should be consistent with the retention time of the main peak of the reference solution.
examination
- the pH value should be 5.5 to 7.5 (General 0631).
- the color of this product shall be inspected according to law (General rule 0901, Law 1), and shall not be deeper than the yellow-green No. 2 Standard Colorimetric solution.
- the related substances were protected from light. Take an appropriate amount of this product with precision, and quantitatively dilute it with mobile phase to make a solution containing about 0.2mg of nimodipine per LML, which is used as the test solution, add the mobile phase to dissolve and quantitatively dilute to make a solution containing about 20ug per lml, take 5ml with precision, put it in a 100ml measuring flask, add 1ml of test solution with precision, dilute to the scale with mobile phase, as a control solution. According to the method of nimodipine related substances. If there are impurity peaks in the chromatogram of the test solution, the peak area shall be calculated according to the external standard method, except for the chromatographic peak whose relative retention time is less than 0.45 and the chromatographic peak whose retention time is consistent with that of impurity I, 0.5% of the labeled amount of nimodipine shall not be exceeded; The peak area of other individual impurities shall not be greater than that of nimodipine in the control solution (1.0%), and the peak area of each impurity (the peak area of impurity I times 1.78) the sum should not be greater than 2 times (2.0%) the area of the nimodipine peak in the control solution. The chromatogram of the test solution is 0.02 times smaller than the main peak area of the control solution.
- pyrogen to take this product, according to the law (General 1142), the dose of rabbit body weight per lkg slow injection of 2.5, should comply with the provisions.
- sterile take this product, by membrane filtration method, inspection according to law (General 1101), should comply with the provisions.
- others should comply with the relevant provisions under injection (General 0102).
Content determination
- measured by high performance liquid chromatography (General 0512).
- chromatographic conditions and system suitability test using eighteen alkyl silane bonded silica gel as filler; Methanol-acetonitrile-water (35:38:27) as mobile phase; The detection wavelength was 235Nm. The number of theoretical plates shall not be less than 8000 calculated by nimodipine peak, and the degree of separation between nimodipine peak and adjacent impurity peaks shall meet the requirements.
- The assay was operated in the dark. Take 5ml of this product with precision, put it in 50ml measuring flask, dilute it to scale with mobile phase, shake well, take 1UL with precision, inject it into liquid chromatograph, record chromatogram; Take nimodipine reference substance, precision weighing, plus mobile phase dissolution and quantitative dilution of about 20% per lml solution, the same method, according to the external standard method to calculate the peak area, that is.
category
Same as nimodipine.
specification
(l)10ml:2mg (2)20ml:4mg(3)40ml:8mg (4)50ml:1Omg
storage
light shielding, closed storage.
Last Update：2022-01-01 11:42:37
1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-3,5-pyridinedicarboxylic acid 2-methoxyethyl 1-methylethyl ester - Nimodipine Capsules
Authoritative Data Verified Data
This product contains Nimodipine (C21H26N207) should be 90.0% to 110.0% of the label.
trait
The contents of this product are yellowish to yellowish granules or powder.
identification
- take an appropriate amount of the contents of this product (about 40mg of nimodipine), add 5ml of ethanol, shake to dissolve nimodipine, filter, and take about 3ml of the filtrate, add 2ml of newly prepared 5% ammonium ferrous sulfate solution, add 1 drop of 1.5mol/L sulfuric acid solution and 1ml of 0.5mol /L potassium hydroxide solution, shake strongly, and change the precipitate from gray-green to red-brown within 1 minute.
- in the chromatogram recorded under the content determination item, the retention time of the main peak of the test solution should be consistent with the retention time of the main peak of the reference solution.
examination
- the related substances were protected from light. Take the appropriate amount of fine powder (about equivalent to 10 mg of nimodipine) under the content determination item, weigh it accurately, put it in a 50ml measuring flask, add the appropriate amount of mobile phase, sonicate for about 15 minutes to dissolve nimodipine, and let it cool, dilute to the scale with mobile phase, shake, centrifuge for 10 minutes (3000 rpm), take the supernatant as the test solution; Take the impurity I control, precision weighing, add the mobile phase to dissolve and quantitatively dilute to make a solution containing about 20ug per lml, take 5ml with precision, put it in a 100ml measuring flask, add 1ml of test solution with precision, dilute to the scale with mobile phase, as a control solution. According to the method of nimodipine related substances. If there are impurity peaks in the chromatogram of the test solution, the peak area shall be calculated according to the external standard method, except for the chromatographic peak whose relative retention time is less than 0.35 and the chromatographic peak whose retention time is consistent with that of impurity I, 0.5% of the labeled amount of nimodipine shall not be exceeded; The peak area of other individual impurities shall not be greater than that of nimodipine in the control solution (1.0%), and the peak area of each impurity (the peak area of impurity I times 1.78) the sum should not be greater than 2 times (2.0%) the area of the nimodipine peak in the control solution. The chromatogram of the test solution is 0.02 times smaller than the main peak area of the control solution.
- Content uniformity (20mg specification) protected from light. Take 1 capsule of this product, pour the contents into a 100ml measuring flask, wash the capsule shell with about 50ml of mobile phase, wash the liquid and the flask, according to the method under the content determination item, from "ultrasonic about 15 minutes to dissolve nimodipine", the content shall be determined according to law, and shall comply with the regulations (General rule 0941).
- dissolution rate protected from light. Take this product, according to the dissolution and release determination method (General 0931 second method), with acetate buffer solution (take sodium acetate 0.299g, add water 50ml, shake to dissolve, add glacial acetic acid 0.174g, dilute to 4.5 ml with water and shake well to obtain pH 0.3% (containing sodium dodecyl sulfate) ml as dissolution medium, rotate at 75 rpm, take 10ml of continuous filtrate accurately, put it in a 20ml(20mg specification) or 25ml(30mg specification) measuring flask, dilute to the scale with dissolution medium, shake well, and use it as a test solution; add about 10mg of nimodipine reference product to a 100ml measuring flask, add 10ml of ethanol, shake to dissolve, dilute to scale with dissolution medium, shake well, and take 5ml, in a 50ml measuring flask, add the dissolution medium to dilute to the scale, shake, as a reference solution. Take the test solution and the reference solution, according to the UV-visible spectrophotometry (General rule 0401), at the wavelength of 238nm, respectively, the absorbance was measured, and the dissolution amount of each particle was calculated, the limit is 80% of the labeled amount and shall be in accordance with the provisions.
- others should comply with the relevant provisions under the capsule (General 0103).
determination of content
- measured by high performance liquid chromatography (General 0512).
- chromatographic conditions and system applicability test using eighteen alkyl silane bonded silica as filler, methanol-acetonitrile-water (35:38:27) as mobile phase, the detection wavelength was 235nm, the number of theoretical plates shall not be less than 8000 calculated by nimodipine peak, and the degree of separation between nimodipine peak and adjacent impurity peaks shall meet the requirements.
- The assay was operated in the dark. Take 20 capsules of this product, precision weighing, calculate the average loading, take the content (20mg specification) or take the content under the difference of the amount, grind, mix evenly, add appropriate amount of mobile phase into 50ml measuring flask. Sonicate for about 15 minutes to dissolve nididipine, let it cool, and dilute to scale with mobile phase, shake well, centrifuge for 10 minutes (3000 revolutions per minute), Take 5ml of the liquid, put it in a 50ml measuring flask, dilute it to the scale with mobile phase, shake well, and use it as a test solution, 10 u1 was accurately measured and injected into the liquid chromatograph to record the chromatogram. Another nimodipine reference substance was accurately weighed, dissolved and quantitatively diluted with mobile phase to prepare a solution containing about 20ug per 1 ml, which was determined by the same method. According to the external standard method to calculate the peak area, that is.
category
Same as nimodipine.
specification
(l)20mg (2)30mg
storage
shading, sealed preservation
Last Update：2022-01-01 11:42:38
Supplier List
Spot supply
Product Name: Nimodipine Visit Supplier Webpage Request for quotationCAS: 66085-59-4
Tel: 0714-3999186
Email: 2853786052@qq.com
Mobile: 86+15671228036
QQ: 2853786052
Wechat: 15671228036
Multiple SpecificationsSpot supply
Product Name: Nimodipine Visit Supplier Webpage Request for quotationCAS: 66085-59-4
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
Wechat: 18301782025
Spot supply
Product Name: Nimodipine Visit Supplier Webpage Request for quotationCAS: 66085-59-4
Tel: 0714-3999186
Email: 2853786052@qq.com
Mobile: 86+15671228036
QQ: 2853786052
Wechat: 15671228036
Multiple SpecificationsSpot supply
Product Name: Nimodipine Visit Supplier Webpage Request for quotationCAS: 66085-59-4
Tel: 18301782025
Email: 3008007409@qq.com
Mobile: 18021002903
QQ: 3008007409
Wechat: 18301782025
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