{"id":2256,"date":"2025-09-22T13:16:19","date_gmt":"2025-09-22T06:16:19","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=2256"},"modified":"2025-10-03T16:55:48","modified_gmt":"2025-10-03T09:55:48","slug":"aminophylline-hydrate","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/aminophylline-hydrate\/","title":{"rendered":"Aminophylline Hydrate"},"content":{"rendered":"

(Theophylline-Ethylenediamine Hydrate, Ph. Eur. monograph 0301)<\/em><\/p>\n

C16<\/sub>H24<\/sub>N10<\/sub>O4<\/sub>, xH2<\/sub>O\u00a0 \u00a0 420.4\u00a0 \u00a0(anhydrous substance)\u00a0 \u00a072487-55-9<\/p>\n

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

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

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

Aminophylline Injection<\/p>\n

Aminophylline Tablets<\/p>\n

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

DEFINITION<\/h2>\n

Content<\/h3>\n

\u2014 theophylline (C7<\/sub>H8<\/sub>N4<\/sub>O2<\/sub>; Mr 180.2): 84.0 per cent to 87.4 per cent (anhydrous substance);<\/p>\n

\u2014 ethylenediamine (C2<\/sub>H8<\/sub>N2<\/sub>; Mr 60.1): 13.5 per cent to 15.0 per cent (anhydrous substance).<\/p>\n

It contains a variable quantity of water.<\/p>\n

CHARACTERS<\/h2>\n

Appearance<\/h3>\n

White or slightly yellowish powder, sometimes granular.<\/p>\n

Solubility<\/h3>\n

Freely soluble in water (the solution becomes cloudy through absorption of carbon dioxide), practically insoluble in anhydrous ethanol.<\/p>\n

IDENTIFICATION<\/h2>\n

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

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

Dissolve 1.0 g in 10 mL of water R and add 2 mL of dilute hydrochloric acid R dropwise with shaking. Filter. Use the precipitate for identification test A and the filtrate for identification test C.<\/p>\n

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

Preparation: Precipitate, washed with water R and dried at 105 \u00b0C.<\/p>\n

Comparison: theophylline CRS.<\/p>\n

B. Thin-layer chromatography (2.2.27).<\/p>\n

Test solution: Dissolve 0.2 g of the substance to be examined in 2 mL of water R with heating and dilute to 10 mL with methanol R.<\/p>\n

Reference solution: Dissolve 0.2 g of theophylline CRS in 2 mL of water R with heating and dilute to 10 mL with methanol R.<\/p>\n

Plate: TLC silica gel F254 plate R.<\/p>\n

Mobile phase concentrated ammonia R, acetone R, methylene chloride R, butanol R (10:30:30:40 V\/V\/V\/V).<\/p>\n

Application: 10 \u03bcL.<\/p>\n

Development: Over 3\/4 of the plate.<\/p>\n

Drying: In air.<\/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

C. To the filtrate add 0.2 mL of benzoyl chloride R, make alkaline with dilute sodium hydroxide solution R and shake vigorously. Filter the precipitate, wash with 10 mL of water R, dissolve in 5 mL of hot ethanol (96 per cent) R and add 5 mL of water R. A precipitate is formed which, when washed and dried at 105\u00b0C, melts (2.2.14) at 248\u00b0C to 252\u00b0C.<\/p>\n

D. Dissolve 30 mg of the substance to be examined in 3 mL of water R and add 0.5 mL of a 10 g\/L solution of copper sulfate pentahydrate R. A violet-purple colour is produced.<\/p>\n

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

TESTS<\/h2>\n

Appearance of solution<\/h3>\n

The solution is not more opalescent than reference suspension II (2.2.1) and not more intensely coloured than reference solution GY6 (2.2.2, Method II).<\/p>\n

Dissolve 0.5 g with gentle warming in 10 mL of carbon dioxide-free water R.<\/p>\n

Related substances<\/h3>\n

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

Test solution: Dissolve 50 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): 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 10 mg of theobromine R (impurity G) 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: irregular octadecylsilyl silica gel for chromatography R (7 \u03bcm).<\/p>\n

Mobile phase: Mix 7 volumes of acetonitrile R and 93 volumes of a 1.36 g\/L solution of sodium acetate R containing 0.50 per cent V\/V of glacial acetic acid R.<\/p>\n

Flow rate: 2.0 mL\/min.<\/p>\n

Detection: Spectrophotometer at 272 nm.<\/p>\n

Injection: 20 \u03bcL.<\/p>\n

Run time: 3.5 times the retention time of theophylline.<\/p>\n

Identification of impurities: Use the chromatogram obtained with reference solution (b) to identify the peak due to impurity G.
\nRelative retention With reference to theophylline (retention time = about 6 min): impurity G = about 0.6.<\/p>\n

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

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

Limits:<\/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 the area of the principal peak in the chromatogram obtained with reference solution (a) (0.1 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

3.0 per cent to 8.0 per cent, determined on 0.500 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

Ethylenediamine<\/h3>\n

Dissolve 0.250 g in 30 mL of water R. Add 0.1 mL of bromocresol green solution R. Titrate with 0.1 M hydrochloric acid until a green colour is obtained.<\/p>\n

1 mL of 0.1 M hydrochloric acid is equivalent to 3.005 mg of C2<\/sub>H8<\/sub>N2<\/sub>.<\/p>\n

Theophylline<\/h3>\n

Heat 0.200 g to constant mass in an oven at 135 \u00b0C. Dissolve the residue with heating in 100 mL of water R, allow to cool, 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 C7<\/sub>H8<\/sub>N4<\/sub>O2<\/sub>.<\/p>\n

STORAGE<\/h2>\n

In a well-filled, airtight container, 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 Substances for pharmaceutical use (2034).<\/p>\n

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, C, D, E, F, G.<\/p>\n

\"Aminophylline<\/p>\n

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

\"Aminophylline<\/p>\n

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

\"Aminophylline<\/p>\n

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

\"Aminophylline<\/p>\n

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

\"Aminophylline<\/p>\n

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

\"Aminophylline<\/p>\n

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

\"Aminophylline<\/p>\n

G. 3,7-dimethyl-3,7-dihydro-1H-purine-2,6-dione (theobromine).<\/p>\n","protected":false},"excerpt":{"rendered":"

(Theophylline-Ethylenediamine Hydrate, Ph. Eur. monograph 0301) C16H24N10O4, xH2O\u00a0 \u00a0 420.4\u00a0 \u00a0(anhydrous substance)\u00a0 \u00a072487-55-9 Action and use Non-selective phosphodiesterase inhibitor; treatment of reversible airways obstruction. Preparations Aminophylline Injection Aminophylline Tablets Aminophylline Prolonged-release Tablets DEFINITION Content \u2014 theophylline (C7H8N4O2; Mr 180.2): 84.0 per cent to 87.4 per cent (anhydrous substance); \u2014 ethylenediamine (C2H8N2; Mr 60.1): 13.5 per…<\/p>\n","protected":false},"author":4,"featured_media":7481,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-2256","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\/2256","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\/4"}],"replies":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/comments?post=2256"}],"version-history":[{"count":8,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/2256\/revisions"}],"predecessor-version":[{"id":8668,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/2256\/revisions\/8668"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/7481"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=2256"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=2256"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=2256"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}