{"id":12626,"date":"2025-10-11T11:15:37","date_gmt":"2025-10-11T04:15:37","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=12626"},"modified":"2025-10-11T11:15:37","modified_gmt":"2025-10-11T04:15:37","slug":"ethosuximide","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/ethosuximide\/","title":{"rendered":"Ethosuximide"},"content":{"rendered":"

(Ph. Eur. monograph 0764)<\/p>\n

C_{7<\/sub>H_{11<\/sub>NO_{2<\/sub>\u00a0 \u00a0 \u00a0 \u00a0141.2\u00a0 \u00a0 \u00a0 \u00a0 77-67-8<\/p>\n}}}

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

Antiepileptic.<\/p>\n

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

Ethosuximide Capsules<\/p>\n

Ethosuximide Oral Solution<\/p>\n

DEFINITION<\/h2>\n
(3RS)-3-Ethyl-3-methylpyrrolidine-2,5-dione.<\/p>\n
Content<\/h3>\n
99.0 per cent to 101.0 per cent (anhydrous substance).<\/p>\n
CHARACTERS<\/h2>\n
Appearance<\/h3>\n
White or almost white, powder or waxy solid.<\/p>\n
Solubility<\/h3>\n
Freely soluble in water, very soluble in ethanol (96 per cent) and in methylene chloride.<\/p>\n
It shows polymorphism (5.9).<\/p>\n
IDENTIFICATION<\/h2>\n
First identification: A, B.<\/p>\n
Second identification: A, C.<\/p>\n
A. Melting point (2.2.14): 45 \u00b0C to 50 \u00b0C.<\/p>\n
B. Infrared absorption spectrophotometry (2.2.24).<\/p>\n
Comparison: ethosuximide CRS.<\/p>\n
If the spectra obtained in the solid state show differences, dissolve the substance to be examined and the reference substance separately in methylene chloride R, evaporate to dryness and record new spectra using the residues.<\/p>\n
C. Thin-layer chromatography (2.2.27).<\/p>\n
Test solution: Dissolve 20 mg of the substance to be examined in 1 mL of methanol R.<\/p>\n
Reference solution: Dissolve 20 mg of ethosuximide CRS in 1 mL of methanol R.<\/p>\n
Plate: TLC silica gel F254 plate R.<\/p>\n
Mobile phase: glacial acetic acid R, water R, butanol R (17:17:66 V\/V\/V).<\/p>\n
Application: 5 \u03bcL.<\/p>\n
Development: Over 3\/4 of the plate.<\/p>\n
Drying: At 100-105 \u00b0C for 10 min.<\/p>\n
Detection: Examine in ultraviolet light at 254 nm.<\/p>\n
Results: The principal spot in the chromatogram obtained with the test solution is similar in position and size to the principal spot in the chromatogram obtained with the reference solution.<\/p>\n
TESTS<\/h2>\n
Appearance of solution<\/h3>\n
The solution is clear (2.2.1) and colourless (2.2.2, Method II).<\/p>\n
Dissolve 2.5 g in water R and dilute to 25 mL with the same solvent.<\/p>\n
Cyanide<\/h3>\n
Liquid chromatography (2.2.29).<\/p>\n
Test solution: Dissolve 0.50 g of the substance to be examined in water R and dilute to 10.0 mL with the same solvent.<\/p>\n
Reference solution (a): Dissolve 0.125 g of potassium cyanide R in water R and dilute to 50.0 mL with the same solvent. Dilute 1.0 mL of the solution to 100.0 mL with water R. Dilute 0.5 mL of this solution to 10.0 mL with water R.<\/p>\n
Reference solution (b): Dissolve 0.50 g of the substance to be examined in water R, add 0.5 mL of reference solution (a) and dilute to 10.0 mL with water R.<\/p>\n
Column:<\/p>\n
\u2014 size: l = 0.075 m, \u00d8 = 7.5 mm,<\/p>\n
\u2014 stationary phase: spherical weak anion-exchange resin R (10 \u03bcm).<\/p>\n
Mobile phase: Dissolve 2.1 g of lithium hydroxide R and 85 mg of sodium edetate R in water for chromatography R, and dilute to 1000 mL with the same solvent.<\/p>\n
Flow rate: 2.0 mL\/min.<\/p>\n
Detection: Electrochemical detector (direct amperometry) with a silver working electrode, a silver-silver chloride reference electrode, held at + 0.05 V oxidation potential, and a detector sensitivity of 20 nA full scale.<\/p>\n
Injection: 20 \u03bcL of the test solution and reference solution (b).<\/p>\n
System suitability: Reference solution (b):<\/p>\n
\u2014 peak-to-valley ratio: minimum 3, where Hp = height above the baseline of the peak due to cyanide and H_{v<\/sub> = height above the baseline of the lowest point of the curve separating this peak from the peak due to ethosuximide.<\/p>\n}
Limit:<\/p>\n
\u2014 cyanide: not more than 0.5 times the height of the corresponding peak in the chromatogram obtained with reference solution (b) (0.5 ppm).<\/p>\n
Related substances<\/h3>\n
Liquid chromatography (2.2.29).<\/p>\n
Test solution: Dissolve 0.250 g of the substance to be examined in mobile phase A and dilute to 10.0 mL with mobile phase A. Store the solution at room temperature for at least 30 min before injection (in situ transformation of impurity B to impurity A).<\/p>\n
Reference solution (a): Dissolve 5.0 mg of ethosuximide impurity A CRS in mobile phase A and dilute to 10.0 mL with mobile phase A.<\/p>\n
Reference solution (b): Dilute 1.0 mL of reference solution (a) to 20.0 mL with mobile phase A.<\/p>\n
Reference solution (c): Mix 1 mL of reference solution (a) and 4 mL of the test solution.<\/p>\n
Column:<\/p>\n
\u2014 size: l = 0.10 m, \u00d8 = 2.1 mm;<\/p>\n
\u2014 stationary phase: end-capped solid core octadecylsilyl organosilica polymer compatible with 100 per cent aqueous mobile phases R (2.6 \u03bcm);<\/p>\n
\u2014 temperature: 25 \u00b0C.<\/p>\n
Mobile phase:<\/p>\n
\u2014 mobile phase A: 15.6 g\/L solution of sodium dihydrogen phosphate R previously adjusted to pH 2.0 with phosphoric acid R;<\/p>\n
\u2014 mobile phase B: acetonitrile for chromatography R;<\/p>\n\n\n\n\n\n\n
Time<\/strong>
\n(min)<\/strong><\/td>\n Mobile phase A<\/strong>
\n(per cent V\/V)<\/strong><\/td>\n Mobile phase B<\/strong>
\n(per cent V\/V)<\/strong><\/td>\n<\/tr>\n
0 – 10<\/td>\n 90<\/td>\n 10<\/td>\n<\/tr>\n
10 – 11<\/td>\n 90 \u2192 30<\/td>\n 10 \u2192 70<\/td>\n<\/tr>\n
11 – 15<\/td>\n 30<\/td>\n 70<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n
Flow rate: 0.25 mL\/min.<\/p>\n
Detection: Spectrophotometer at 220 nm.<\/p>\n
Injection: 3 \u03bcL of the test solution and reference solutions (b) and (c).<\/p>\n
Identification of impurities: Use the chromatogram obtained with reference solution (b) to identify the peak due to impurity A.<\/p>\n
Relative retention: With reference to ethosuximide (retention time = about 4 min): impurity A = about 1.7.<\/p>\n
System suitability: Reference solution (c):<\/p>\n
\u2014 resolution: minimum 3.0 between the peaks due to ethosuximide and impurity A.<\/p>\n
Calculation of percentage contents:<\/p>\n
\u2014 for each impurity, use the concentration of impurity A in reference solution (b).<\/p>\n
Limits:<\/p>\n
\u2014 unspecified impurities: for each impurity, maximum 0.10 per cent;<\/p>\n
\u2014 total: maximum 0.2 per cent;<\/p>\n
\u2014 reporting threshold: 0.05 per cent.<\/p>\n
Water (2.5.12)<\/h4>\n
Maximum 0.5 per cent, determined on 1.00 g.<\/p>\n
Sulfated ash (2.4.14)<\/h4>\n
Maximum 0.1 per cent, determined on 1.0 g.<\/p>\n
ASSAY<\/h2>\n
Dissolve 0.120 g in 20 mL of dimethylformamide R and carry out a potentiometric titration (2.2.20) using 0.1 M tetrabutylammonium hydroxide. Protect the solution from atmospheric carbon dioxide throughout the titration. Carry out a blank titration.<\/p>\n
1 mL of 0.1 M tetrabutylammonium hydroxide is equivalent to 14.12 mg of C_{7<\/sub>H_{11<\/sub>NO_{2<\/sub>.<\/p>\n}}}
STORAGE<\/h2>\n
Protected from light.<\/p>\n
IMPURITIES<\/h2>\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<\/p>\n
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
$\"Ethosuximide\"$ <\/p>\n
A. (2RS)-2-ethyl-2-methylbutanedioic acid,<\/p>\n
$\"Ethosuximide\"$ <\/p>\n
B. (3RS)-3-ethyl-3-methyldihydrofuran-2,5-dione.<\/p>\n","protected":false},"excerpt":{"rendered":"
(Ph. Eur. monograph 0764) C7H11NO2\u00a0 \u00a0 \u00a0 \u00a0141.2\u00a0 \u00a0 \u00a0 \u00a0 77-67-8 Action and use Antiepileptic. Preparations Ethosuximide Capsules Ethosuximide Oral Solution DEFINITION (3RS)-3-Ethyl-3-methylpyrrolidine-2,5-dione. Content 99.0 per cent to 101.0 per cent (anhydrous substance). CHARACTERS Appearance White or almost white, powder or waxy solid. Solubility Freely soluble in water, very soluble in ethanol (96 per…<\/p>\n","protected":false},"author":2,"featured_media":12641,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-12626","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\/12626","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=12626"}],"version-history":[{"count":2,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/12626\/revisions"}],"predecessor-version":[{"id":12652,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/12626\/revisions\/12652"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/12641"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=12626"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=12626"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=12626"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}

Time<\/strong> \n(min)<\/strong><\/td>\n	Mobile phase A<\/strong> \n(per cent V\/V)<\/strong><\/td>\n	Mobile phase B<\/strong> \n(per cent V\/V)<\/strong><\/td>\n<\/tr>\n
0 – 10<\/td>\n	90<\/td>\n	10<\/td>\n<\/tr>\n
10 – 11<\/td>\n	90 \u2192 30<\/td>\n	10 \u2192 70<\/td>\n<\/tr>\n
11 – 15<\/td>\n	30<\/td>\n	70<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n Flow rate: 0.25 mL\/min.<\/p>\n Detection: Spectrophotometer at 220 nm.<\/p>\n Injection: 3 \u03bcL of the test solution and reference solutions (b) and (c).<\/p>\n Identification of impurities: Use the chromatogram obtained with reference solution (b) to identify the peak due to impurity A.<\/p>\n Relative retention: With reference to ethosuximide (retention time = about 4 min): impurity A = about 1.7.<\/p>\n System suitability: Reference solution (c):<\/p>\n \u2014 resolution: minimum 3.0 between the peaks due to ethosuximide and impurity A.<\/p>\n Calculation of percentage contents:<\/p>\n \u2014 for each impurity, use the concentration of impurity A in reference solution (b).<\/p>\n Limits:<\/p>\n \u2014 unspecified impurities: for each impurity, maximum 0.10 per cent;<\/p>\n \u2014 total: maximum 0.2 per cent;<\/p>\n \u2014 reporting threshold: 0.05 per cent.<\/p>\n Water (2.5.12)<\/h4>\n Maximum 0.5 per cent, determined on 1.00 g.<\/p>\n Sulfated ash (2.4.14)<\/h4>\n Maximum 0.1 per cent, determined on 1.0 g.<\/p>\n ASSAY<\/h2>\n Dissolve 0.120 g in 20 mL of dimethylformamide R and carry out a potentiometric titration (2.2.20) using 0.1 M tetrabutylammonium hydroxide. Protect the solution from atmospheric carbon dioxide throughout the titration. Carry out a blank titration.<\/p>\n 1 mL of 0.1 M tetrabutylammonium hydroxide is equivalent to 14.12 mg of C_{7<\/sub>H_{11<\/sub>NO_{2<\/sub>.<\/p>\n}}} STORAGE<\/h2>\n Protected from light.<\/p>\n IMPURITIES<\/h2>\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<\/p>\n 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 $\"Ethosuximide\"$ <\/p>\n A. (2RS)-2-ethyl-2-methylbutanedioic acid,<\/p>\n $\"Ethosuximide\"$ <\/p>\n B. (3RS)-3-ethyl-3-methyldihydrofuran-2,5-dione.<\/p>\n","protected":false},"excerpt":{"rendered":" (Ph. Eur. monograph 0764) C7H11NO2\u00a0 \u00a0 \u00a0 \u00a0141.2\u00a0 \u00a0 \u00a0 \u00a0 77-67-8 Action and use Antiepileptic. Preparations Ethosuximide Capsules Ethosuximide Oral Solution DEFINITION (3RS)-3-Ethyl-3-methylpyrrolidine-2,5-dione. Content 99.0 per cent to 101.0 per cent (anhydrous substance). CHARACTERS Appearance White or almost white, powder or waxy solid. Solubility Freely soluble in water, very soluble in ethanol (96 per…<\/p>\n","protected":false},"author":2,"featured_media":12641,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-12626","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\/12626","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=12626"}],"version-history":[{"count":2,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/12626\/revisions"}],"predecessor-version":[{"id":12652,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/12626\/revisions\/12652"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/12641"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=12626"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=12626"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=12626"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}

Content<\/h3>\n99.0 per cent to 101.0 per cent (anhydrous substance).<\/p>\n

CHARACTERS<\/h2>\n

Appearance<\/h3>\nWhite or almost white, powder or waxy solid.<\/p>\n

Solubility<\/h3>\nFreely soluble in water, very soluble in ethanol (96 per cent) and in methylene chloride.<\/p>\nIt shows polymorphism (5.9).<\/p>\n

TESTS<\/h2>\n

Appearance of solution<\/h3>\nThe solution is clear (2.2.1) and colourless (2.2.2, Method II).<\/p>\nDissolve 2.5 g in water R and dilute to 25 mL with the same solvent.<\/p>\n

Water (2.5.12)<\/h4>\nMaximum 0.5 per cent, determined on 1.00 g.<\/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
99.0 per cent to 101.0 per cent (anhydrous substance).<\/p>\n

Appearance<\/h3>\n
White or almost white, powder or waxy solid.<\/p>\n

Solubility<\/h3>\n
Freely soluble in water, very soluble in ethanol (96 per cent) and in methylene chloride.<\/p>\n
It shows polymorphism (5.9).<\/p>\n

Appearance of solution<\/h3>\n
The solution is clear (2.2.1) and colourless (2.2.2, Method II).<\/p>\n
Dissolve 2.5 g in water R and dilute to 25 mL with the same solvent.<\/p>\n

Water (2.5.12)<\/h4>\n
Maximum 0.5 per cent, determined on 1.00 g.<\/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