Edition: BP 2025 (Ph. Eur. 11.6 update)<\/p>\n
Action and use<\/strong><\/p>\n Alpha-adrenoceptor agonist.<\/p>\n Preparation <\/strong><\/p>\n Xylometazoline Nasal Drops<\/p>\n 2-[4-(1,1-Dimethylethyl)-2,6-dimethylbenzyl]-4,5-dihydro-1H-imidazole hydrochloride.<\/p>\n Content<\/strong><\/p>\n 99.0 per cent to 101.0 per cent (dried substance).<\/p>\n White or almost white, crystalline powder.<\/p>\n Freely soluble in water, in ethanol (96 per cent) and in methanol.<\/p>\n First identification: A, E.<\/em><\/p>\n Second identification: B, C, D, E.<\/em><\/p>\n A. Infrared absorption spectrophotometry (2.2.24).<\/p>\n Comparison\u00a0 xylometazoline hydrochloride CRS.<\/p>\n B. Thin-layer chromatography (2.2.27).<\/p>\n Test solution\u00a0 Dissolve 20 mg of the substance to be examined in methanol R and dilute to 5 mL with the same solvent.<\/p>\n Reference solution Dissolve 20 mg of xylometazoline hydrochloride CRS in methanol R and dilute to 5 mL with the same solvent.<\/p>\n Plate\u00a0 TLC silica gel G plate R.<\/p>\n Mobile phase concentrated ammonia R, methanol R (5:100 V\/V). Application 5 \u00b5L.<\/p>\n Development\u00a0 Over 2\/3 of the plate.<\/p>\n Drying\u00a0 In air.<\/p>\n Chlorine treatment At the bottom of a chromatographic tank place a beaker containing a mixture of 1 volume of hydrochloric acid R1, 1 volume of water R and 2 volumes of a 15 g\/L solution of potassium permanganate R. Close the tank and allow to stand for 15 min. Place the dried plate in the tank and reclose the tank. Leave the plate in contact with the chlorine vapour for 5 min. Withdraw the plate and place it in a current of cold air until the excess of chlorine is removed and an area of the coating below the points of application does not give a blue colour with a drop of potassium iodide and starch solution R.<\/p>\n Detection\u00a0 Spray with potassium iodide and starch solution R.<\/p>\n Results The principal spot in the chromatogram obtained with the test solution is similar in position, colour and size to the principal spot in the chromatogram obtained with the reference solution.<\/p>\n C. Dissolve about 0.5 mg in 1 mL of methanol R. Add 0.5 mL of a freshly prepared 50 g\/L solution of sodium nitroprusside R and 0.5 mL of a 20 g\/L solution of sodium hydroxide R. Allow to stand for 10 min and add 1 mL of an 80 g\/L solution of sodium hydrogen carbonate R. A violet colour develops.<\/p>\n D. Dissolve 0.2 g in 1 mL of water R, add 2.5 mL of ethanol (96 per cent) R and 2 mL of 1 M sodium hydroxide. Mix thoroughly and examine in ultraviolet light at 365 nm. The solution shows no fluorescence or at most the same fluorescence as a blank solution prepared in the same manner. The identification is not valid unless a solution prepared in the same manner using naphazoline hydrochloride CRS instead of the substance to be examined shows a distinct bluish fluorescence.<\/p>\n E. It gives reaction (a) of chlorides (2.3.1).<\/p>\n The solution is clear (2.2.1) and not more intensely coloured than reference solution Y6 (2.2.2, Method II). Dissolve 2.5 g in water R and dilute to 50.0 mL with the same solvent.<\/p>\n Dissolve 0.25 g in carbon dioxide-free water R and dilute to 25 mL with the same solvent. Add 0.1 mL of methyl red solution R and 0.1 mL of 0.01 M hydrochloric acid.<\/p>\n The solution is red. Not more than 0.2 mL of 0.01 M sodium hydroxide is required to change the colour of the indicator to yellow.<\/p>\n Liquid chromatography (2.2.29).<\/p>\n Test solution Dissolve 50.0 mg of the substance to be examined in water R and dilute to 50.0 mL with the same solvent. Allow to stand for 1 h before injection.<\/p>\n Reference solution (a)\u00a0 Dilute 5.0 mL of the test solution to 100.0 mL with water R. Dilute 2.0 mL of this solution to 100.0 mL with water R.<\/p>\n Reference solution (b)\u00a0 Dissolve 5.0 mg of xylometazoline impurity A CRS and 5 mg of the substance to be examined in water R and dilute to 50.0 mL with the same solvent. Dilute 10.0 mL of this solution to 50.0 mL with water R. Reference solution (c) Dilute 5.0 mL of reference solution (b) to 50.0 mL with water R.<\/p>\n Column:<\/p>\n \u2014 size: l = 0.25 m, \u00d8 = 4.6 mm;<\/p>\n \u2014 stationary phase: end-capped octadecylsilyl silica gel for chromatography with embedded polar groups R (5 \u00b5m).<\/p>\n Mobile phase:<\/p>\n \u2014 mobile phase A: 1.36 g\/L solution of potassium dihydrogen phosphate R adjusted to pH 3.0 with phosphoric acid R;<\/p>\n \u2014 mobile phase B: acetonitrile for chromatography R;<\/p>\n Flow rate\u00a0 1.0 mL\/min.<\/p>\n Detection\u00a0 Spectrophotometer at 220 nm.<\/p>\n Injection\u00a0 10 \u00b5L.<\/p>\n Relative retention\u00a0 With reference to xylometazoline (retention time = about 7.2 min): impurity A = about 0.79.<\/p>\n System suitability\u00a0 Reference solution (b):<\/p>\n \u2014 resolution: minimum 2.5 between the peaks due to impurity A and xylometazoline.<\/p>\n Limits:<\/p>\n \u2014 impurity A: not more than the area of the corresponding peak in the chromatogram obtained with reference solution (c) (0.2 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 (a) (0.10 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 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 Sulfated ash (2.4.14)<\/strong><\/p>\n Maximum 0.1 per cent, determined on 1.0 g.<\/p>\n Dissolve 0.200 g in 25 mL of anhydrous acetic acid R and add 10 mL of acetic anhydride R. Titrate with 0.1 M perchloric acid, determining the end-point potentiometrically (2.2.20).<\/p>\n 1 mL of 0.1 M perchloric acid is equivalent to 28.08 mg of C16<\/sub>H25<\/sub>ClN2<\/sub>.<\/p>\n Protected from light.<\/p>\n Specified impurities\u00a0 A.<\/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 B, C, D, E, F.<\/em><\/p>\n A. N-(2-aminoethyl)-2-[4-(1,1-dimethylethyl)-2,6-dimethylphenyl]acetamide,<\/p>\n B. 2-(chloromethyl)-5-(1,1-dimethylethyl)-1,3-dimethylbenzene,<\/p>\n C. [4-(1,1-dimethylethyl)-2,6-dimethylphenyl]acetonitrile,<\/p>\n D. 1-(1,1-dimethylethyl)-3,5-dimethylbenzene,<\/p>\n E. ethane-1,2-diamine mono(4-methylbenzenesulfonate),<\/p>\n F. [4-(1,1-dimethylethyl)-2,6-dimethylphenyl]acetic acid.<\/p>\n","protected":false},"excerpt":{"rendered":" Edition: BP 2025 (Ph. Eur. 11.6 update) Action and use Alpha-adrenoceptor agonist. Preparation Xylometazoline Nasal Drops DEFINITION 2-[4-(1,1-Dimethylethyl)-2,6-dimethylbenzyl]-4,5-dihydro-1H-imidazole hydrochloride. Content 99.0 per cent to 101.0 per cent (dried substance). CHARACTERS Appearance White or almost white, crystalline powder. Solubility Freely soluble in water, in ethanol (96 per cent) and in methanol. IDENTIFICATION First identification: A, E….<\/p>\n","protected":false},"author":5,"featured_media":31613,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-31609","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\/31609","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=31609"}],"version-history":[{"count":2,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/31609\/revisions"}],"predecessor-version":[{"id":31624,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/31609\/revisions\/31624"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/31613"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=31609"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=31609"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=31609"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}DEFINITION<\/h2>\n
CHARACTERS<\/h2>\n
Appearance<\/h3>\n
Solubility<\/h3>\n
IDENTIFICATION<\/h2>\n
TESTS<\/h2>\n
Appearance of solution<\/h3>\n
Acidity or alkalinity<\/h3>\n
Related substances<\/h3>\n
\n\n
\n Time (min)<\/strong><\/td>\n Mobile phase A (per cent V\/V)<\/strong><\/td>\n Mobile phase B (per cent V\/V)<\/strong><\/td>\n<\/tr>\n \n 0 – 5<\/td>\n 70<\/td>\n 30<\/td>\n<\/tr>\n \n 5 – 20<\/td>\n 70 \u2192 15<\/td>\n 30 \u2192 85<\/td>\n<\/tr>\n \n 20 – 35<\/td>\n 15<\/td>\n 85<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n ASSAY<\/h2>\n
STORAGE<\/h2>\n
IMPURITIES<\/h2>\n