{"id":26958,"date":"2025-11-06T14:52:45","date_gmt":"2025-11-06T07:52:45","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=26958"},"modified":"2025-11-06T20:08:04","modified_gmt":"2025-11-06T13:08:04","slug":"pholcodine-monohydrate","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/pholcodine-monohydrate\/","title":{"rendered":"Pholcodine Monohydrate"},"content":{"rendered":"

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

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

Opioid receptor agonist; cough suppressant.<\/p>\n

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

Pholcodine Linctus<\/p>\n

Strong Pholcodine Linctus<\/p>\n

Ph Eur<\/p>\n

\n

DEFINITION<\/h2>\n

17-Methyl-3-[2-(morpholin-4-yl)ethoxy]-7,8-didehydro-4,5\u03b1-epoxymorphinan-6\u03b1-ol monohydrate.<\/p>\n

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

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

CHARACTERS<\/h2>\n

Appearance<\/h3>\n

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

Solubility<\/h3>\n

Sparingly soluble in water, freely soluble in acetone and in ethanol (96 per cent). It dissolves in dilute mineral acids.<\/p>\n

IDENTIFICATION<\/h2>\n

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

Comparison\u00a0 pholcodine CRS.<\/p>\n

TESTS<\/h2>\n

Specific optical rotation (2.2.7)<\/strong><\/p>\n

-98 to -94 (dried substance).<\/p>\n

Dissolve 1.000 g in ethanol (96 per cent) R and dilute to 50.0 mL with the same solvent.<\/p>\n

Related substances<\/h3>\n

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

0.02 M phosphate buffer solution To 80.0 mL of 0.2 M sodium hydroxide add 100.0 mL of 0.2 M potassium dihydrogen phosphate R and dilute to 1.0 L with water R.<\/p>\n

Solvent mixture\u00a0 Dilute 80 mL of acetonitrile R to 1 L with the 0.02 M phosphate buffer solution.<\/p>\n

Test solution Dissolve 50 mg of the substance to be examined in the solvent mixture and dilute to 50 mL with the solvent mixture.<\/p>\n

Reference solution (a) Dissolve 10 mg of codeine R (impurity B) in the solvent mixture and dilute to 10 mL with the solvent mixture. To 0.5 mL of this solution add 0.5 mL of the test solution and dilute to 50 mL with the solvent mixture.<\/p>\n

Reference solution (b) Dilute 1.0 mL of the test solution to 100.0 mL with the solvent mixture. Dilute 1.0 mL of this solution to 10.0 mL with the solvent mixture.<\/p>\n

Reference solution (c) Dissolve 5 mg of pholcodine for peak identification CRS (containing impurities A, B and D) in the solvent mixture and dilute to 5 mL with the solvent mixture.<\/p>\n

Reference solution (d) Dissolve 5 mg of pholcodine for impurity G identification CRS in the solvent mixture and dilute to 5 mL with the solvent mixture.<\/p>\n

Column:<\/p>\n

\u2014 size: l = 0.075 m, \u00d8 = 4.6 mm;<\/p>\n

\u2014 stationary phase: end-capped solid core phenylhexylsilyl silica gel for chromatography R (2.6 \u00b5m);<\/p>\n

\u2014 temperature: 35 \u00b0C.<\/p>\n

Mobile phase To 50 mL of tetrahydrofuran for chromatography R add 75 mL of acetonitrile R and dilute to 1000 mL with the 0.02 M phosphate buffer solution; adjust to pH 7.9 \u00b1 0.05 with 0.2 M sodium hydroxide; the pH must not exceed 8.0.<\/p>\n

Flow rate\u00a0 1.0 mL\/min.<\/p>\n

Detection\u00a0 Spectrophotometer at 238 nm.<\/p>\n

Injection\u00a0 20 \u00b5L.<\/p>\n

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

Identification of impurities Use the chromatogram supplied with pholcodine for peak identification CRS and the chromatogram obtained with reference solution (c) to identify the peaks due to impurities A, B and D; use the chromatogram obtained with reference solution (d) to identify the peak due to impurity G.<\/p>\n

Relative retention With reference to pholcodine (retention time = about 10 min): impurity A = about 0.4; impurity B = about 0.8; impurity D = about 2.3; impurity G = about 4.2.<\/p>\n

System suitability\u00a0 Reference solution (a):<\/p>\n

\u2014 resolution: minimum 3.0 between the peaks due to impurity B and pholcodine.<\/p>\n

Limits:<\/p>\n

\u2014 correction factor: for the calculation of content, multiply the peak area of impurity G by 0.5;<\/p>\n

\u2014 impurities A, B, D: for each impurity, not more than twice the area of the principal peak in the chromatogram obtained with reference solution (b) (0.2 per cent);<\/p>\n

\u2014 impurity G: not more than 1.5 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 the area of the principal peak in the chromatogram obtained with reference solution (b) (0.10 per cent);<\/p>\n

\u2014 total: not more than 7 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.7 per cent);<\/p>\n

\u2014 disregard limit: 0.5 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.05 per cent).<\/p>\n

Loss on drying (2.2.32)<\/strong><\/p>\n

3.9 per cent to 4.5 per cent, determined on 0.500 g by drying in an oven at 105 \u00b0C.<\/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 0.180 g in 50 mL of anhydrous acetic acid R, warming gently. Titrate with 0.1 M perchloric acid, determining the end-point potentiometrically (2.2.20).
\n1 mL of 0.1 M perchloric acid is equivalent to 19.93 mg of C23H30N2O4.<\/p>\n

IMPURITIES<\/h2>\n

Specified impurities\u00a0 A, B, D, G.<\/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) C, E, F.<\/p>\n

\"Pholcodine<\/p>\n

A. 17-methyl-7,8-didehydro-4,5\u03b1-epoxymorphinan-3,6\u03b1-diol (morphine),<\/p>\n

\"Pholcodine<\/p>\n

B. 3-methoxy-17-methyl-7,8-didehydro-4,5\u03b1-epoxymorphinan-6\u03b1-ol (codeine),<\/p>\n

\"Pholcodine<\/p>\n

C. (17RS)-6\u03b1-hydroxy-17-methyl-3-[2-(morpholin-4-yl)ethoxy]-7,8-didehydro-4,5\u03b1-epoxymorphinan 17-oxide (pholcodine N-oxide),<\/p>\n

\"Pholcodine<\/p>\n

D. 17-methyl-3,6\u03b1-bis[2-(morpholin-4-yl)ethoxy]-7,8-didehydro-4,5\u03b1-epoxymorphinan,<\/p>\n

\"Pholcodine<\/p>\n

E. 4-[2-[(6\u03b1-hydroxy-17-methyl-7,8-didehydro-4,5\u03b1-epoxymorphinan-3-yl)oxy]ethyl]morpholine 4-oxide (pholcodine N\u2032- oxide),<\/p>\n

\"Pholcodine<\/p>\n

F. (17RS)-6\u03b1-hydroxy-17-methyl-3-[2-(4-oxidomorpholin-4-ium-4-yl)ethoxy]-7,8-didehydro-4,5\u03b1-epoxymorphinan 17- oxide (pholcodine N,N\u2032-dioxide),<\/p>\n

\"Pholcodine<\/p>\n

G. 17,17\u02b9-dimethyl-3,3\u02b9-bis[2-(morpholin-4-yl)ethoxy]-7,7\u02b9,8,8\u02b9-tetradehydro-4,5\u03b1:4\u02b9,5\u02b9\u03b1-diepoxybimorphinan-6\u03b1,6\u02b9\u03b1-diol\u00a0 \u00a0(pholcodine dimer).<\/p>\n

\n

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

Edition: BP 2025 (Ph. Eur. 11.6 update) Action and use Opioid receptor agonist; cough suppressant. Preparations Pholcodine Linctus Strong Pholcodine Linctus Ph Eur DEFINITION 17-Methyl-3-[2-(morpholin-4-yl)ethoxy]-7,8-didehydro-4,5\u03b1-epoxymorphinan-6\u03b1-ol monohydrate. Content 98.5 per cent to 101.5 per cent (dried substance). CHARACTERS Appearance White or almost white, crystalline powder or colourless crystals. Solubility Sparingly soluble in water, freely soluble in…<\/p>\n","protected":false},"author":5,"featured_media":26983,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-26958","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\/26958","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=26958"}],"version-history":[{"count":4,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/26958\/revisions"}],"predecessor-version":[{"id":27468,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/26958\/revisions\/27468"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/26983"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=26958"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=26958"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=26958"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}