{"id":29732,"date":"2025-11-11T08:44:52","date_gmt":"2025-11-11T01:44:52","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=29732"},"modified":"2025-11-11T08:44:52","modified_gmt":"2025-11-11T01:44:52","slug":"theophylline-hydrate","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/theophylline-hydrate\/","title":{"rendered":"Theophylline Hydrate"},"content":{"rendered":"

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

(Theophylline Monohydrate, Ph. Eur. monograph 0302)<\/p>\n

\"Theophylline<\/p>\n

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

Non-selective phosphodiesterase inhibitor (xanthine); treatment of reversible airways obstruction.<\/p>\n

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

Aminophylline Injection<\/p>\n

Theophylline Prolonged-release Tablets<\/p>\n

Ph Eur<\/p>\n

DEFINITION<\/h2>\n

1,3-Dimethyl-3,7-dihydro-1H-purine-2,6-dione monohydrate.<\/p>\n

Content<\/strong><\/p>\n

99.0 per cent to 101.0 per cent (anhydrous substance).<\/p>\n

CHARACTERS<\/h2>\n

Appearance<\/h3>\n

White or almost white, crystalline powder.<\/p>\n

Solubility<\/h3>\n

Slightly soluble in water, sparingly soluble in ethanol (96 per cent). It dissolves in solutions of alkali hydroxides, in ammonia and in mineral acids.<\/p>\n

IDENTIFICATION<\/h2>\n

First identification: B, D.<\/p>\n

Second identification: A, C, D, E.<\/p>\n

A. Melting point (2.2.14): 270 \u00b0C to 274 \u00b0C, determined after drying at 100-105 \u00b0C.<\/p>\n

B. Infrared absorption spectrophotometry (2.2.24).<\/p>\n

Preparation Dry the substance to be examined at 100-105 \u00b0C before use.<\/p>\n

Comparison Ph. Eur. reference spectrum of theophylline.<\/p>\n

C. Heat 10 mg with 1.0 mL of a 360 g\/L solution of potassium hydroxide R in a water-bath at 90 \u00b0C for 3 min, then add 1.0 mL of diazotised sulfanilic acid solution R. A red colour slowly develops. Carry out a blank test.<\/p>\n

D. Water (see Tests).<\/p>\n

E. It gives the reaction of xanthines (2.3.1).<\/p>\n

TESTS<\/h2>\n

Solution S<\/h3>\n

Dissolve 0.5 g with heating in carbon dioxide-free water R, cool and dilute to 75 mL with the same solvent.<\/p>\n

Appearance of solution<\/h3>\n

Solution S is clear (2.2.1) and colourless (2.2.2, Method II).<\/p>\n

Acidity<\/h3>\n

To 50 mL of solution S add 0.1 mL of methyl red solution R. The solution is red. Not more than 1.0 mL of 0.01 M sodium hydroxide is required to change the colour of the indicator to yellow.<\/p>\n

Related substances<\/h3>\n

Liquid chromatography (2.2.29).<\/p>\n

Test solution\u00a0 \u00a0Dissolve 40.0 mg of the substance to be examined in the mobile phase and dilute to 20.0 mL with the mobile phase.<\/p>\n

Reference solution (a)\u00a0 \u00a0Dilute 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)\u00a0 \u00a0Dissolve 10 mg of theobromine R in the mobile phase, add 5 mL of the test solution and dilute to 100 mL with the mobile phase. Dilute 5 mL of this solution to 50 mL with the mobile phase.<\/p>\n

Column:<\/p>\n

\u2014 size: l = 0.25 m, \u00d8 = 4 mm;<\/p>\n

\u2014 stationary phase: octadecylsilyl silica gel for chromatography R (7 \u03bcm).<\/p>\n

Mobile phase\u00a0 \u00a0Mix 7 volumes of acetonitrile for chromatography R and 93 volumes of a 1.36 g\/L solution of sodium acetate R containing 5.0 mL\/L of glacial acetic acid R.<\/p>\n

Flow rate\u00a0 \u00a02.0 mL\/min.<\/p>\n

Detection\u00a0 \u00a0Spectrophotometer at 272 nm.<\/p>\n

Injection\u00a0 \u00a020 \u03bcL.<\/p>\n

Run time\u00a0 \u00a03.5 times the retention time of theophylline.<\/p>\n

Relative retention\u00a0 \u00a0With reference to theophylline (retention time = about 6 min): impurity C = about 0.3; impurity B = about 0.4; impurity D = about 0.5; impurity A = about 2.5.<\/p>\n

System suitability\u00a0 \u00a0Reference solution (b):<\/p>\n

\u2014 resolution: minimum 2.0 between the peaks due to theobromine and theophylline.<\/p>\n

Limits:<\/p>\n

\u2014 impurities A, B, C, D: for each impurity, not more than the area of the principal peak in the chromatogram obtained with reference solution (a) (0.1 per cent);<\/p>\n

\u2014 any other impurity: for each impurity, not more than the area of the principal peak in the chromatogram obtained with reference solution (a) (0.1 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

Water (2.5.12)<\/h3>\n

8.0 per cent to 9.5 per cent, determined on 0.20 g.<\/p>\n

Sulfated ash (2.4.14)<\/h3>\n

Maximum 0.1 per cent, determined on 1.0 g.<\/p>\n

ASSAY<\/h2>\n

Dissolve 0.160 g in 100 mL of water R, add 20 mL of 0.1 M silver nitrate and shake. Add 1 mL of bromothymol blue solution R1. Titrate with 0.1 M sodium hydroxide.<\/p>\n

1 mL of 0.1 M sodium hydroxide is equivalent to 18.02 mg of C7H8N4O2<\/p>\n

IMPURITIES<\/h2>\n

Specified impurities A, B, C, D.<\/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) E, F.<\/p>\n

\"Theophylline<\/p>\n

A. 1,3,7-trimethyl-3,7-dihydro-1H-purine-2,6-dione (caffeine),<\/p>\n

\"Theophylline<\/p>\n

\"Theophylline<\/p>\n

C. N-(6-amino-1,3-dimethyl-2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)formamide,<\/p>\n

\"Theophylline<\/p>\n

D. N-methyl-5-(methylamino)-1H-imidazole-4-carboxamide (theophyllidine),<\/p>\n

\"Theophylline<\/p>\n

E. 1,3-dimethyl-7,9-dihydro-1H-purine-2,6,8(3H)-trione,<\/p>\n

\"Theophylline<\/p>\n

F. 7-(2-hydroxyethyl)-1,3-dimethyl-3,7-dihydro-1H-purine-2,6-dione (etofylline).<\/p>\n

Ph Eur<\/p>\n","protected":false},"excerpt":{"rendered":"

Edition: BP 2025 (Ph. Eur. 11.6 update) (Theophylline Monohydrate, Ph. Eur. monograph 0302) Action and use Non-selective phosphodiesterase inhibitor (xanthine); treatment of reversible airways obstruction. Preparations Aminophylline Injection Theophylline Prolonged-release Tablets Ph Eur DEFINITION 1,3-Dimethyl-3,7-dihydro-1H-purine-2,6-dione monohydrate. Content 99.0 per cent to 101.0 per cent (anhydrous substance). CHARACTERS Appearance White or almost white, crystalline powder. Solubility…<\/p>\n","protected":false},"author":5,"featured_media":29733,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-29732","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\/29732","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=29732"}],"version-history":[{"count":2,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/29732\/revisions"}],"predecessor-version":[{"id":29743,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/29732\/revisions\/29743"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/29733"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=29732"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=29732"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=29732"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}