{"id":25509,"date":"2025-11-04T15:24:22","date_gmt":"2025-11-04T08:24:22","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=25509"},"modified":"2025-11-04T15:24:22","modified_gmt":"2025-11-04T08:24:22","slug":"nimodipine","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/nimodipine\/","title":{"rendered":"Nimodipine"},"content":{"rendered":"

(Ph. Eur. monograph 1245)<\/p>\n

C_{21<\/sub>H_{26<\/sub>N_{2<\/sub>O_{7<\/sub>\u00a0 \u00a0 \u00a0 \u00a0 \u00a0 418.4\u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a066085-59-4<\/p>\n}}}}

Action and use<\/strong><\/p>\n

Calcium channel blocker.<\/p>\n

Preparations<\/strong><\/p>\n

Nimodipine Infusion<\/p>\n

Nimodipine Tablets<\/p>\n

DEFINITION<\/h2>\n
2-Methoxyethyl 1-methylethyl (4RS)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.<\/p>\n
Content<\/h3>\n
98.5 per cent to 101.5 per cent (dried substance).<\/p>\n
CHARACTERS<\/h2>\n
Appearance<\/h3>\n
Light yellow or yellow, crystalline powder.<\/p>\n
Solubility<\/h3>\n
Practically insoluble in water, freely soluble in ethyl acetate, sparingly soluble in anhydrous ethanol.<\/p>\n
It shows polymorphism (5.9).<\/p>\n
Exposure to ultraviolet light leads to the formation of a nitrophenylpyridine derivative.<\/p>\n
IDENTIFICATION<\/h2>\n
A. Optical rotation (see Tests).<\/p>\n
B. Infrared absorption spectrophotometry (2.2.24).<\/p>\n
Comparison: nimodipine CRS.<\/p>\n
If the spectra obtained in the solid state show differences, record new spectra using 20 g\/L solutions in methylene chloride R and a 0.2 mm cell.<\/p>\n
TESTS<\/h2>\n
Prepare solutions immediately before use either protected from light or under long-wavelength light (> 420 nm).<\/p>\n
Solution S<\/h3>\n
Dissolve 1.0 g in acetone R and dilute to 20.0 mL with the same solvent.<\/p>\n
Appearance of solution<\/h3>\n
Solution S is clear (2.2.1).<\/p>\n
Optical rotation (2.2.7)<\/h4>\n
-0.10\u00b0 to + 0.10\u00b0, determined on solution S.<\/p>\n
Related substances<\/h3>\n
Liquid chromatography (2.2.29).<\/p>\n
Test solution: Dissolve 40 mg of the substance to be examined in 2.5 mL of tetrahydrofuran R and dilute to 25.0 mL with the mobile phase.<\/p>\n
Reference solution (a): Dilute 1.0 mL of the test solution to 100.0 mL with the mobile phase. Dilute 1.0 mL of this solution to 10.0 mL with the mobile phase.<\/p>\n
Reference solution (b): Dissolve 4 mg of nimodipine for peak identification CRS (containing impurity C) in 0.25 mL of tetrahydrofuran R and dilute to 2.5 mL with the mobile phase.<\/p>\n
Reference solution (c): Dilute 0.5 mL of the test solution to 25.0 mL with the mobile phase. Mix 0.5 mL of this solution with 0.5 mL of nimodipine impurity A CRS and dilute to 10.0 mL with the mobile phase.<\/p>\n
Column:<\/p>\n
\u2014 size: l = 0.125 m, \u00d8 = 4.6 mm;<\/p>\n
\u2014 stationary phase: end-capped octadecylsilyl silica gel for chromatography R (5 \u03bcm);<\/p>\n
\u2014 temperature: 40 \u00b0C.<\/p>\n
Mobile phase: methanol R, tetrahydrofuran R, water R (20:20:60 V\/V\/V).<\/p>\n
Flow rate: 2.0 mL\/min.<\/p>\n
Detection: Spectrophotometer at 235 nm.<\/p>\n
Injection: 20 \u03bcL.<\/p>\n
Run time: 4.5 times the retention time of nimodipine.<\/p>\n
Identification of impurities: Use the chromatogram supplied with nimodipine for peak identification CRS and the chromatogram obtained with reference solution (b) to identify the peak due to impurity C; use the chromatogram obtained with reference solution (c) to identify the peak due to impurity A.<\/p>\n
Relative retention: With reference to nimodipine (retention time = about 7 min): impurity C = about 0.5; impurity A = about 0.9.<\/p>\n
System suitability: Reference solution (c):<\/p>\n
\u2014 peak-to-valley ratio: minimum 4.0, where Hp = height above the baseline of the peak due to impurity A and Hv = height above the baseline of the lowest point of the curve separating this peak from the peak due to nimodipine.<\/p>\n
Limits:<\/p>\n
\u2014 impurity C: not more than twice the area of the principal peak in the chromatogram obtained with reference solution (a) (0.2 per cent);<\/p>\n
\u2014 unspecified impurities : for each impurity, not more than the area of the principal peak in the chromatogram obtained with reference solution (a) (0.10 per cent);<\/p>\n
\u2014 total: not more than 5 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.5 per cent);<\/p>\n
\u2014 disregard limit: 0.5 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.05 per cent).<\/p>\n
Loss on drying (2.2.32)<\/h4>\n
Maximum 0.5 per cent, determined on 1.000 g by drying in an oven at 105 \u00b0C.<\/p>\n
Sulfated ash (2.4.14)<\/h4>\n
Maximum 0.1 per cent, determined on 1.0 g.<\/p>\n
ASSAY<\/h2>\n
Prepare solutions immediately before use either protected from light or under long-wavelength light (> 420 nm).<\/p>\n
Dissolve with gentle heating 0.180 g in a mixture of 25 mL of 2-methyl-2-propanol R and 25 mL of perchloric acid solution R. Add 0.1 mL of ferroin R. Titrate with 0.1 M cerium sulfate. Titrate slowly towards the end of the titration. Carry out a blank titration.<\/p>\n
1 mL of 0.1 M cerium sulfate is equivalent to 20.92 mg of C_{21<\/sub>H_{26<\/sub>N_{2<\/sub>O_{7<\/sub>.<\/p>\n}}}}
STORAGE<\/h2>\n
Protected from light.<\/p>\n
IMPURITIES<\/h2>\n
Specified impurities C.<\/p>\n
Other detectable impurities (the following substances would, if present at a sufficient level, be detected by one or other of the tests in the monograph. They are limited by the general acceptance criterion for other\/unspecified impurities and\/or by the general monograph Substances for pharmaceutical use (2034). It is therefore not necessary to identify these impurities for demonstration of compliance. See also 5.10. Control of impurities in substances for pharmaceutical use) A, B.<\/p>\n
$\"Nimodipine\"$ <\/p>\n
A. 2-methoxyethyl 1-methylethyl 2,6-dimethyl-4-(3-nitrophenyl)pyridine-3,5-dicarboxylate,<\/p>\n
$\"Nimodipine\"$ <\/p>\n
B. bis(1-methylethyl) 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate,<\/p>\n
$\"Nimodipine\"$ <\/p>\n
C. bis(2-methoxyethyl) 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate.<\/p>\n","protected":false},"excerpt":{"rendered":"
(Ph. Eur. monograph 1245) C21H26N2O7\u00a0 \u00a0 \u00a0 \u00a0 \u00a0 418.4\u00a0 \u00a0 \u00a0 \u00a0 \u00a0 \u00a066085-59-4 Action and use Calcium channel blocker. Preparations Nimodipine Infusion Nimodipine Tablets DEFINITION 2-Methoxyethyl 1-methylethyl (4RS)-2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate. Content 98.5 per cent to 101.5 per cent (dried substance). CHARACTERS Appearance Light yellow or yellow, crystalline powder. Solubility Practically insoluble in water, freely soluble…<\/p>\n","protected":false},"author":2,"featured_media":25535,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-25509","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-medicinal-substances"],"acf":[],"_links":{"self":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/25509","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/comments?post=25509"}],"version-history":[{"count":2,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/25509\/revisions"}],"predecessor-version":[{"id":25537,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/25509\/revisions\/25537"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/25535"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=25509"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=25509"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=25509"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}

Content<\/h3>\n98.5 per cent to 101.5 per cent (dried substance).<\/p>\n

CHARACTERS<\/h2>\n

Appearance<\/h3>\nLight yellow or yellow, crystalline powder.<\/p>\n

Solubility<\/h3>\nPractically insoluble in water, freely soluble in ethyl acetate, sparingly soluble in anhydrous ethanol.<\/p>\nIt shows polymorphism (5.9).<\/p>\nExposure to ultraviolet light leads to the formation of a nitrophenylpyridine derivative.<\/p>\n

TESTS<\/h2>\nPrepare solutions immediately before use either protected from light or under long-wavelength light (> 420 nm).<\/p>\n

Solution S<\/h3>\nDissolve 1.0 g in acetone R and dilute to 20.0 mL with the same solvent.<\/p>\n

Appearance of solution<\/h3>\nSolution S is clear (2.2.1).<\/p>\n

Optical rotation (2.2.7)<\/h4>\n-0.10\u00b0 to + 0.10\u00b0, determined on solution S.<\/p>\n

Loss on drying (2.2.32)<\/h4>\nMaximum 0.5 per cent, determined on 1.000 g by drying in an oven at 105 \u00b0C.<\/p>\n

Sulfated ash (2.4.14)<\/h4>\nMaximum 0.1 per cent, determined on 1.0 g.<\/p>\n

STORAGE<\/h2>\nProtected from light.<\/p>\n

Content<\/h3>\n
98.5 per cent to 101.5 per cent (dried substance).<\/p>\n

Appearance<\/h3>\n
Light yellow or yellow, crystalline powder.<\/p>\n

Solubility<\/h3>\n
Practically insoluble in water, freely soluble in ethyl acetate, sparingly soluble in anhydrous ethanol.<\/p>\n
It shows polymorphism (5.9).<\/p>\n
Exposure to ultraviolet light leads to the formation of a nitrophenylpyridine derivative.<\/p>\n

TESTS<\/h2>\n
Prepare solutions immediately before use either protected from light or under long-wavelength light (> 420 nm).<\/p>\n

Solution S<\/h3>\n
Dissolve 1.0 g in acetone R and dilute to 20.0 mL with the same solvent.<\/p>\n

Appearance of solution<\/h3>\n
Solution S is clear (2.2.1).<\/p>\n

Optical rotation (2.2.7)<\/h4>\n
-0.10\u00b0 to + 0.10\u00b0, determined on solution S.<\/p>\n

Loss on drying (2.2.32)<\/h4>\n
Maximum 0.5 per cent, determined on 1.000 g by drying in an oven at 105 \u00b0C.<\/p>\n

Sulfated ash (2.4.14)<\/h4>\n
Maximum 0.1 per cent, determined on 1.0 g.<\/p>\n

STORAGE<\/h2>\n
Protected from light.<\/p>\n