{"id":30963,"date":"2025-11-12T16:34:13","date_gmt":"2025-11-12T09:34:13","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=30963"},"modified":"2025-11-12T16:34:13","modified_gmt":"2025-11-12T09:34:13","slug":"valproic-acid","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/valproic-acid\/","title":{"rendered":"Valproic Acid"},"content":{"rendered":"

Edition: BP 2025 (Ph. Eur. 11.6 update)<\/p>\n

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

Antiepileptic.<\/p>\n

DEFINITION<\/h2>\n
2-Propylpentanoic acid.<\/p>\n
Content<\/strong><\/p>\n
99.0 per cent to 101.0 per cent.<\/p>\n
CHARACTERS<\/h2>\n
Appearance<\/h3>\n
Colourless or very slightly yellow, clear liquid, slightly viscous.<\/p>\n
Solubility<\/h3>\n
Very slightly soluble in water, miscible with ethanol (96 per cent) and with methylene chloride. It dissolves in dilute solutions of alkali hydroxides.<\/p>\n
IDENTIFICATION<\/h2>\n
Infrared absorption spectrophotometry (2.2.24).<\/p>\n
Comparison\u00a0 valproic acid CRS.<\/p>\n
TESTS<\/h2>\n
Appearance of solution<\/h3>\n
The solution is clear (2.2.1) and not more intensely coloured than reference solution Y5 (2.2.2, Method II). Dissolve 2.0 g in dilute sodium hydroxide solution R and dilute to 10 mL with the same alkaline solution.<\/p>\n
Related substances<\/h3>\n
Gas chromatography (2.2.28).<\/p>\n
Test solution Dissolve 0.500 g of the substance to be examined in heptane R and dilute to 100.0 mL with the same solvent.<\/p>\n
Reference solution (a)\u00a0 Dissolve 5 mg of valproic acid for system suitability CRS (containing impurity K) in 1.0 mL of heptane R.<\/p>\n
Reference solution (b) Dilute 1.0 mL of the test solution to 100.0 mL with heptane R. Column:<\/p>\n
\u2014 material: wide-bore fused silica;<\/p>\n
\u2014 size: l = 30 m, \u00d8 = 0.53 mm;<\/p>\n
\u2014 stationary phase: macrogol 20 000 2-nitroterephthalate R (film thickness 0.5 \u00b5m).<\/p>\n
Carrier gas helium for chromatography R. Flow rate 8 mL\/min.<\/p>\n
Temperature:<\/p>\n\n\n\n\n\n\n\n\n\n
<\/td>\n Time (min)<\/strong><\/td>\n Temperature (\u00b0C)<\/strong><\/td>\n<\/tr>\n
Column<\/td>\n 0 – 5<\/td>\n 80<\/td>\n<\/tr>\n
<\/td>\n 5 – 15<\/td>\n 80 \u2192 150<\/td>\n<\/tr>\n
<\/td>\n 15 – 28.3<\/td>\n 150 \u2192 190<\/td>\n<\/tr>\n
<\/td>\n 28.3 – 30<\/td>\n 190<\/td>\n<\/tr>\n
Injection port<\/td>\n 220<\/td>\n<\/tr>\n
Detector<\/td>\n 220<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n
Detection\u00a0 Flame ionisation.<\/p>\n
Injection\u00a0 1 \u00b5L.<\/p>\n
Relative retention\u00a0 With reference to valproic acid (retention time = about 17 min): impurity K = about 0.97.<\/p>\n
System suitability\u00a0 Reference solution (a):<\/p>\n
\u2014 resolution: minimum 2.0 between the peaks due to impurity K and valproic acid.<\/p>\n
Limits:<\/p>\n
\u2014 impurity K: not more than 0.15 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.15 per cent);<\/p>\n
\u2014 unspecified impurities: for each impurity, not more than 0.05 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.05 per cent);<\/p>\n
\u2014 total: not more than 0.2 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.2 per cent);<\/p>\n
\u2014 disregard limit: 0.03 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.03 per cent).<\/p>\n
Sulfated ash (2.4.14)<\/strong><\/p>\n
Maximum 0.1 per cent, determined on 1.0 g.<\/p>\n
ASSAY<\/h2>\n
Dissolve 0.100 g in 25 mL of ethanol (96 per cent) R. Add 2 mL of water R. Titrate with 0.1 M sodium hydroxide, determining the end-point potentiometrically (2.2.20).<\/p>\n
1 mL of 0.1 M sodium hydroxide is equivalent to 14.42 mg of C_{8<\/sub>H_{16<\/sub>O_{2<\/sub>.<\/p>\n}}}
STORAGE<\/h2>\n
In an airtight container.<\/p>\n
IMPURITIES<\/h2>\n
Specified impurities\u00a0 K.<\/em><\/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)\u00a0 A, B, C, D, E, F, G, H, I, J, L.<\/em><\/p>\n
A. pentanoic acid (valeric acid),<\/p>\n
B. (2RS)-2-ethylpentanoic acid,<\/p>\n
C. (2RS)-2-(1-methylethyl)pentanoic acid,<\/p>\n
D. 2,2-dipropylpentanoic acid,<\/p>\n
E. pentanamide (valeramide),<\/p>\n
F. 2-propylpentanamide,<\/p>\n
G. 2,2-dipropylpentanamide,<\/p>\n
H. pentanenitrile (valeronitrile),<\/p>\n
I. 2-propylpentanenitrile,<\/p>\n
J. 2,2-dipropylpentanenitrile,<\/p>\n
K. (2RS)-2-ethyl-2-methylpentanoic acid,<\/p>\n
L. (2RS)-2-methylpentanoic acid.<\/p>\n","protected":false},"excerpt":{"rendered":"
Edition: BP 2025 (Ph. Eur. 11.6 update) Action and use Antiepileptic. DEFINITION 2-Propylpentanoic acid. Content 99.0 per cent to 101.0 per cent. CHARACTERS Appearance Colourless or very slightly yellow, clear liquid, slightly viscous. Solubility Very slightly soluble in water, miscible with ethanol (96 per cent) and with methylene chloride. It dissolves in dilute solutions of…<\/p>\n","protected":false},"author":5,"featured_media":30964,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-30963","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\/30963","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\/5"}],"replies":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/comments?post=30963"}],"version-history":[{"count":2,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/30963\/revisions"}],"predecessor-version":[{"id":30982,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/30963\/revisions\/30982"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/30964"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=30963"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=30963"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=30963"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}

<\/td>\n	Time (min)<\/strong><\/td>\n	Temperature (\u00b0C)<\/strong><\/td>\n<\/tr>\n
Column<\/td>\n	0 – 5<\/td>\n	80<\/td>\n<\/tr>\n
<\/td>\n	5 – 15<\/td>\n	80 \u2192 150<\/td>\n<\/tr>\n
<\/td>\n	15 – 28.3<\/td>\n	150 \u2192 190<\/td>\n<\/tr>\n
<\/td>\n	28.3 – 30<\/td>\n	190<\/td>\n<\/tr>\n
Injection port<\/td>\n	220<\/td>\n<\/tr>\n
Detector<\/td>\n	220<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n Detection\u00a0 Flame ionisation.<\/p>\n Injection\u00a0 1 \u00b5L.<\/p>\n Relative retention\u00a0 With reference to valproic acid (retention time = about 17 min): impurity K = about 0.97.<\/p>\n System suitability\u00a0 Reference solution (a):<\/p>\n \u2014 resolution: minimum 2.0 between the peaks due to impurity K and valproic acid.<\/p>\n Limits:<\/p>\n \u2014 impurity K: not more than 0.15 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.15 per cent);<\/p>\n \u2014 unspecified impurities: for each impurity, not more than 0.05 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.05 per cent);<\/p>\n \u2014 total: not more than 0.2 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.2 per cent);<\/p>\n \u2014 disregard limit: 0.03 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.03 per cent).<\/p>\n Sulfated ash (2.4.14)<\/strong><\/p>\n Maximum 0.1 per cent, determined on 1.0 g.<\/p>\n ASSAY<\/h2>\n Dissolve 0.100 g in 25 mL of ethanol (96 per cent) R. Add 2 mL of water R. Titrate with 0.1 M sodium hydroxide, determining the end-point potentiometrically (2.2.20).<\/p>\n 1 mL of 0.1 M sodium hydroxide is equivalent to 14.42 mg of C_{8<\/sub>H_{16<\/sub>O_{2<\/sub>.<\/p>\n}}} STORAGE<\/h2>\n In an airtight container.<\/p>\n IMPURITIES<\/h2>\n Specified impurities\u00a0 K.<\/em><\/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)\u00a0 A, B, C, D, E, F, G, H, I, J, L.<\/em><\/p>\n A. pentanoic acid (valeric acid),<\/p>\n B. (2RS)-2-ethylpentanoic acid,<\/p>\n C. (2RS)-2-(1-methylethyl)pentanoic acid,<\/p>\n D. 2,2-dipropylpentanoic acid,<\/p>\n E. pentanamide (valeramide),<\/p>\n F. 2-propylpentanamide,<\/p>\n G. 2,2-dipropylpentanamide,<\/p>\n H. pentanenitrile (valeronitrile),<\/p>\n I. 2-propylpentanenitrile,<\/p>\n J. 2,2-dipropylpentanenitrile,<\/p>\n K. (2RS)-2-ethyl-2-methylpentanoic acid,<\/p>\n L. (2RS)-2-methylpentanoic acid.<\/p>\n","protected":false},"excerpt":{"rendered":" Edition: BP 2025 (Ph. Eur. 11.6 update) Action and use Antiepileptic. DEFINITION 2-Propylpentanoic acid. Content 99.0 per cent to 101.0 per cent. CHARACTERS Appearance Colourless or very slightly yellow, clear liquid, slightly viscous. Solubility Very slightly soluble in water, miscible with ethanol (96 per cent) and with methylene chloride. It dissolves in dilute solutions of…<\/p>\n","protected":false},"author":5,"featured_media":30964,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-30963","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\/30963","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\/5"}],"replies":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/comments?post=30963"}],"version-history":[{"count":2,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/30963\/revisions"}],"predecessor-version":[{"id":30982,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/30963\/revisions\/30982"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/30964"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=30963"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=30963"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=30963"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}

Appearance<\/h3>\nColourless or very slightly yellow, clear liquid, slightly viscous.<\/p>\n

Solubility<\/h3>\nVery slightly soluble in water, miscible with ethanol (96 per cent) and with methylene chloride. It dissolves in dilute solutions of alkali hydroxides.<\/p>\n

IDENTIFICATION<\/h2>\nInfrared absorption spectrophotometry (2.2.24).<\/p>\nComparison\u00a0 valproic acid CRS.<\/p>\n

TESTS<\/h2>\n

Appearance of solution<\/h3>\nThe solution is clear (2.2.1) and not more intensely coloured than reference solution Y5 (2.2.2, Method II). Dissolve 2.0 g in dilute sodium hydroxide solution R and dilute to 10 mL with the same alkaline solution.<\/p>\n

STORAGE<\/h2>\nIn an airtight container.<\/p>\n

Appearance<\/h3>\n
Colourless or very slightly yellow, clear liquid, slightly viscous.<\/p>\n

Solubility<\/h3>\n
Very slightly soluble in water, miscible with ethanol (96 per cent) and with methylene chloride. It dissolves in dilute solutions of alkali hydroxides.<\/p>\n

IDENTIFICATION<\/h2>\n
Infrared absorption spectrophotometry (2.2.24).<\/p>\n
Comparison\u00a0 valproic acid CRS.<\/p>\n

Appearance of solution<\/h3>\n
The solution is clear (2.2.1) and not more intensely coloured than reference solution Y5 (2.2.2, Method II). Dissolve 2.0 g in dilute sodium hydroxide solution R and dilute to 10 mL with the same alkaline solution.<\/p>\n

STORAGE<\/h2>\n
In an airtight container.<\/p>\n