{"id":26953,"date":"2025-11-06T14:34:05","date_gmt":"2025-11-06T07:34:05","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=26953"},"modified":"2025-11-06T18:56:51","modified_gmt":"2025-11-06T11:56:51","slug":"oxitropium-bromide","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/oxitropium-bromide\/","title":{"rendered":"Oxitropium Bromide"},"content":{"rendered":"

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

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

Anticholinergic; treatment of reversible airways obstruction. Ph Eur<\/p>\n

DEFINITION<\/h2>\n

(1R,2R,4S,5S,7s,9s)-9-Ethyl-7-[[(2S)-3-hydroxy-2-phenylpropanoyl]oxy]-9-methyl-3-oxa-9-\u00a0 azoniatricyclo[3.3.1.02,4]nonane bromide (ethylhyoscine).<\/p>\n

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

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

CHARACTERS<\/h2>\n

Appearance<\/h3>\n

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

Solubility<\/h3>\n

Very soluble in water, freely soluble in methanol, sparingly soluble in ethanol (96 per cent), practically insoluble in methylene chloride.<\/p>\n

It shows polymorphism (5.9).<\/p>\n

IDENTIFICATION<\/h2>\n

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

Comparison\u00a0 oxitropium bromide CRS.<\/p>\n

If the spectra obtained in the solid state show differences at about 1700 cm-1 and about 3300 cm-1, dissolve the substance to be examined and the reference substance separately in methanol R, evaporate to dryness and record new spectra using the residues.<\/p>\n

B. It gives reaction (a) of bromides (2.3.1).<\/p>\n

TESTS<\/h2>\n

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

-26 to -24 (dried substance).<\/p>\n

Dissolve 1.0 g in water R and dilute to 20.0 mL with the same solvent.<\/p>\n

Related substances<\/h3>\n

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

Test solution\u00a0 Dissolve 75.0 mg of the substance to be examined in the mobile phase and dilute to 50.0 mL with the mobile phase. Dilute 5.0 mL of the solution to 50.0 mL with the mobile phase.<\/p>\n

Reference solution (a)\u00a0 Dissolve 7.5 mg of oxitropium bromide impurity B CRS in the mobile phase and dilute to 50.0 mL with the mobile phase.<\/p>\n

Reference solution (b)\u00a0 Dilute 5.0 mL of reference solution (a) to 50.0 mL with the mobile phase. Dilute 5.0 mL of this solution to 50.0 mL with the mobile phase. Dilute 5.0 mL of this solution to 50.0 mL with the mobile phase.<\/p>\n

Reference solution (c)\u00a0 Mix 5.0 mL of the test solution and 5.0 mL of reference solution (a).<\/p>\n

Reference solution (d)\u00a0 Dilute 15.0 mL of the test solution to 100.0 mL with the mobile phase. Dilute 5.0 mL of this solution to 50.0 mL with the mobile phase.<\/p>\n

Reference solution (e)\u00a0 Dilute 5.0 mL of the test solution to 50.0 mL with the mobile phase. Dilute 5.0 mL of this solution to 50.0 mL with the mobile phase. Dilute 5.0 mL of this solution to 50.0 mL with the mobile phase.<\/p>\n

Column:<\/p>\n

\u2014 size: l = 0.125 m, \u00d8 = 4.0 mm;<\/p>\n

\u2014 stationary phase: base-deactivated octylsilyl silica gel for chromatography R (5 \u00b5m) with a specific surface area of 350 m2\/g and a pore size of 6 nm.<\/p>\n

Mobile phase\u00a0 acetonitrile for chromatography R, 7.8 g\/L solution of sodium dihydrogen phosphate R(10:100 V\/V).<\/p>\n

Flow rate\u00a0 2.0 mL\/min.<\/p>\n

Detection\u00a0 Spectrophotometer at 210 nm.<\/p>\n

Injection\u00a0 50 \u00b5L of the test solution and reference solutions (b), (c), (d) and (e).<\/p>\n

Relative retention\u00a0 With reference to oxitropium (retention time = about 6 min): impurity A = about 0.8; impurity B = about 0.9; impurity C = about 1.3.<\/p>\n

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

\u2014 resolution: minimum 1.6 between the peaks due to impurity B and oxitropium.<\/p>\n

Limits:<\/p>\n

\u2014 impurity A: not more than the area of the principal peak in the chromatogram obtained with reference solution (e) (0.1 per cent);<\/p>\n

\u2014 impurity B: not more than the area of the corresponding peak in the chromatogram obtained with reference solution (b) (0.1 per cent);<\/p>\n

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

\u2014 sum of unspecified impurities: not more than twice the area of the principal peak in the chromatogram obtained with reference solution (e) (0.2 per cent);<\/p>\n

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

Impurity D<\/h3>\n

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

Test solution\u00a0 Dissolve 75.0 mg of the substance to be examined in the mobile phase and dilute to 50.0 mL with the mobile phase. Dilute 5.0 mL of the solution to 50.0 mL with the mobile phase.<\/p>\n

Reference solution (a)\u00a0 Dissolve 6.0 mg of oxitropium bromide impurity D CRS in the mobile phase and dilute to 50.0 mL with the mobile phase.<\/p>\n

Reference solution (b)\u00a0 Dilute 5.0 mL of reference solution (a) to 200.0 mL with the mobile phase. Dilute 5.0 mL of this solution to 50.0 mL with the mobile phase.<\/p>\n

Reference solution (c)\u00a0 To 5.0 mL of the test solution add 5.0 mL of reference solution (a).<\/p>\n

Column:<\/p>\n

\u2014 size: l = 0.125 m, \u00d8 = 4.0 mm;<\/p>\n

\u2014 stationary phase: base-deactivated octylsilyl silica gel for chromatography R (5 \u00b5m).<\/p>\n

Mobile phase\u00a0 acetonitrile for chromatography R, 7.8 g\/L solution of sodium dihydrogen phosphate R(18.5:100 V\/V).<\/p>\n

Flow rate\u00a0 2.0 mL\/min.<\/p>\n

Detection\u00a0 Spectrophotometer at 210 nm.<\/p>\n

Injection\u00a0 50 \u00b5L of the test solution and reference solutions (b) and (c).<\/p>\n

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

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

Limit:<\/p>\n

\u2014 impurity D: not more than the area of the corresponding peak in the chromatogram obtained with reference solution (b) (0.2 per cent).<\/p>\n

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

Maximum 0.5 per cent, determined on 1.000 g by drying in an oven at 105 \u00b0C.<\/p>\n

ASSAY<\/h2>\n

Dissolve 0.350 g in 100 mL of water R and add 5.0 mL of dilute nitric acid R. Titrate with 0.1 M silver nitrate. Determine the end-point potentiometrically (2.2.20) using a silver indicator electrode and a silver-silver chloride reference electrode.<\/p>\n

1 mL of 0.1 M silver nitrate is equivalent to 41.23 mg of C19<\/sub>H26<\/sub>BrNO4<\/sub>.<\/p>\n

IMPURITIES<\/p>\n

Specified impurities\u00a0 A, B, C, D.<\/p>\n

\"Oxitropium<\/p>\n

A. (1R,2R,4S,5S,7s)-9-ethyl-3-oxa-9-azatricyclo[3.3.1.02,4]non-7-yl (2S)-3-hydroxy-2-phenylpropanoate (N- ethylnorhyoscine),<\/p>\n

\"Oxitropium<\/p>\n

B. (1R,2R,4S,5S,7s)-7-[[(2S)-3-hydroxy-2-phenylpropanoyl]oxy]-9,9-dimethyl-3-oxa-9-\u00a0 azoniatricyclo[3.3.1.02,4]nonane (methylhyoscine),<\/p>\n

\"Oxitropium<\/p>\n

C. (1R,2R,4S,5S,7s,9r)-9-ethyl-7-[[(2S)-3-hydroxy-2-phenylpropanoyl]oxy]-9-methyl-3-oxa-9-\u00a0 azoniatricyclo[3.3.1.02,4]nonane (pseudo-isomer),<\/p>\n

\"Oxitropium<\/p>\n

D. (1R,2R,4S,5S,7s,9s)-9-ethyl-9-methyl-7-[(2-phenylacryloyl)oxy]-3-oxa-9-azoniatricyclo[3.3.1.02,4]nonane\u00a0 (apo-N-ethylhyoscine).<\/p>\n

\n

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

Edition: BP 2025 (Ph. Eur. 11.6 update) Action and use Anticholinergic; treatment of reversible airways obstruction. Ph Eur DEFINITION (1R,2R,4S,5S,7s,9s)-9-Ethyl-7-[[(2S)-3-hydroxy-2-phenylpropanoyl]oxy]-9-methyl-3-oxa-9-\u00a0 azoniatricyclo[3.3.1.02,4]nonane bromide (ethylhyoscine). Content 99.0 per cent to 101.0 per cent (dried substance). CHARACTERS Appearance White or almost white, crystalline powder. Solubility Very soluble in water, freely soluble in methanol, sparingly soluble in ethanol (96…<\/p>\n","protected":false},"author":5,"featured_media":26954,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-26953","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\/26953","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=26953"}],"version-history":[{"count":4,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/26953\/revisions"}],"predecessor-version":[{"id":27433,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/26953\/revisions\/27433"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/26954"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=26953"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=26953"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=26953"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}