Edition: BP 2025 (Ph. Eur. 11.6 update)<\/p>\n
Action and use<\/strong><\/p>\n Selective oestrogen receptor modulator.<\/p>\n Content<\/strong><\/p>\n 97.5 per cent to 102.0 per cent (dried substance).<\/p>\n Almost white or pale-yellow powder.<\/p>\n Very slightly soluble or practically insoluble in water and in acetone, slightly soluble in ethanol (96 per cent V\/V).<\/p>\n A. Infrared absorption spectrophotometry (2.2.24).<\/p>\n Comparison\u00a0 raloxifene hydrochloride CRS.<\/p>\n B. Dissolve 20 mg of the substance to be examined in 2 mL of methanol R. The solution gives reaction (a) of chlorides (2.3.1).<\/p>\n Liquid chromatography (2.2.29).<\/p>\n Solvent mixture\u00a0 acetonitrile R, mobile phase A (30:70 V\/V).<\/p>\n Test solution Dissolve 30 mg of the substance to be examined in the solvent mixture and dilute to 10.0 mL with the solvent mixture.<\/p>\n Reference solution (a) 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 (b) In order to produce impurity C in situ, to 6 mg of the substance to be examined add 15 mL of acetonitrile R, 3 mL of water R and 5 mL of stabilised strong hydrogen peroxide solution R. Store at 30 \u00b0C for at least 6 h then dilute to 50.0 mL with mobile phase A. To 1.0 mL of this solution add 3 mg of the substance to be examined dissolved in the solvent mixture and dilute to 10.0 mL with the solvent mixture.<\/p>\n Reference solution (c) Dissolve 3 mg of raloxifene for peak identification CRS (containing impurity A) in the solvent mixture and dilute to 10.0 mL with the solvent mixture.<\/p>\n Column:<\/p>\n \u2014 size: l = 0.25 m, \u00d8 = 4.6 mm;<\/p>\n \u2014 stationary phase: base-deactivated octylsilyl silica gel for chromatography R (5 \u00b5m);<\/p>\n \u2014 temperature: 35 \u00b0C.<\/p>\n Mobile phase:<\/p>\n \u2014 mobile phase A: 9.0 g\/L solution of potassium dihydrogen phosphate R adjusted to pH 3.0 with phosphoric acid R;<\/p>\n \u2014 mobile phase B: acetonitrile R;<\/p>\n Flow rate\u00a0 1.0 mL\/min.<\/p>\n Detection\u00a0 Spectrophotometer at 280 nm.<\/p>\n Injection\u00a0 10 \u00b5L.<\/p>\n Identification of impurity A Use the chromatogram supplied with raloxifene for peak identification CRS and the chromatogram obtained with reference solution (c) to identify the peak due to impurity A.<\/p>\n Relative retention With reference to raloxifene (retention time = about 18 min): impurity A = about 0.7; impurity C = about 1.2.<\/p>\n System suitability\u00a0 Reference solution (b):<\/p>\n \u2014 resolution: minimum 3.0 between the peaks due to raloxifene and impurity C.<\/p>\n Limits:<\/p>\n \u2014 impurity A: not more than twice the area of the principal peak in the chromatogram obtained with reference solution (a) (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 Maximum 0.5 per cent, determined on 1.000 g by drying in an oven at 105 \u00b0C for 3 h.<\/p>\n Maximum 0.1 per cent determined on 1.0 g.<\/p>\n Liquid chromatography (2.2.29).<\/p>\n Buffer solution pH 2.5\u00a0 7.2 g\/L solution of potassium dihydrogen phosphate R adjusted to pH 2.5 with phosphoric acid R.<\/p>\n Test solution Dissolve 50.0 mg of the substance to be examined in the mobile phase and dilute 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 (a) Dissolve 50.0 mg of raloxifene hydrochloride CRS in the mobile phase and dilute 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 (b) In order to produce impurity C in situ, to 6 mg of the substance to be examined add 15 mL of acetonitrile R, 3 mL of water R and 5 mL of stabilised strong hydrogen peroxide solution R. Store at 30 \u00b0C for at least 6 h, then dilute to 50.0 mL with buffer solution pH 2.5.<\/p>\n Column:<\/p>\n \u2014 size: l = 0.15 m, \u00d8 = 4.6 mm;<\/p>\n \u2014 stationary phase: octylsilyl silica gel for chromatography R2 (3.5 \u00b5m);<\/p>\n \u2014 temperature: 35 \u00b0C.<\/p>\n Mobile phase acetonitrile R, buffer solution pH 2.5 (33:67 V\/V). Flow rate 1.5 mL\/min.<\/p>\n Detection\u00a0 Spectrophotometer at 280 nm.<\/p>\n Injection\u00a0 10 \u00b5L.<\/p>\n Run time\u00a0 Twice the retention time of raloxifene.<\/p>\n Relative retention\u00a0 With reference to raloxifene (retention time = about 3 min): impurity C = about 1.2.<\/p>\n System suitability\u00a0 Reference solution (b):<\/p>\n \u2014 resolution: minimum 2.0 between the peaks due to raloxifene and impurity C; if necessary, adjust the concentration of acetonitrile in the mobile phase.<\/p>\n Calculate the percentage content of C28<\/sub>H28<\/sub>ClNO4<\/sub>S taking into account the assigned content of raloxifene hydrochloride CRS.<\/p>\n Specified impurities\u00a0 A.<\/em> A. [6-hydroxy-2-(4-hydroxyphenyl)-7-[4-[2-(piperidin-1-yl)ethoxy]benzoyl]-1-benzothiophen-3-yl][4-[2-(piperidin-1- yl)ethoxy]phenyl]methanone,<\/p>\n B. [6-hydroxy-2-(4-hydroxyphenyl)-1-benzothiophen-7-yl][4-[2-(piperidin-1-yl)ethoxy]phenyl]methanone,<\/p>\n C. [6-hydroxy-2-(4-hydroxyphenyl)-1-benzothiophen-3-yl][4-[2-(piperidin-1-yl)ethoxy]phenyl]methanone N-oxide.<\/p>\n","protected":false},"excerpt":{"rendered":" Edition: BP 2025 (Ph. Eur. 11.6 update) Action and use Selective oestrogen receptor modulator. DEFINITION [6-Hydroxy-2-(4-hydroxyphenyl)-1-benzothiophen-3-yl][4-[2-(piperidin-1-yl)ethoxy]phenyl]methanone hydrochloride. Content 97.5 per cent to 102.0 per cent (dried substance). CHARACTERS Appearance Almost white or pale-yellow powder. Solubility Very slightly soluble or practically insoluble in water and in acetone, slightly soluble in ethanol (96 per cent V\/V). IDENTIFICATION…<\/p>\n","protected":false},"author":5,"featured_media":28843,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-28842","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\/28842","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=28842"}],"version-history":[{"count":2,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/28842\/revisions"}],"predecessor-version":[{"id":28846,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/28842\/revisions\/28846"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/28843"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=28842"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=28842"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=28842"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}DEFINITION<\/h2>\n[6-Hydroxy-2-(4-hydroxyphenyl)-1-benzothiophen-3-yl][4-[2-(piperidin-1-yl)ethoxy]phenyl]methanone hydrochloride.<\/p>\n
CHARACTERS<\/h2>\n
Appearance<\/h3>\n
Solubility<\/h3>\n
IDENTIFICATION<\/h2>\n
TESTS<\/h2>\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 – 9<\/td>\n 75<\/td>\n 25<\/td>\n<\/tr>\n \n 9 – 40<\/td>\n 75 \u2192 50<\/td>\n 25 \u2192 50<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n Loss on drying (2.2.32)<\/h4>\n
Sulfated ash (2.4.14)<\/h4>\n
ASSAY<\/h2>\n
IMPURITIES<\/h2>\n
\n\u00a0<\/em>
\nOther 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) B, C.<\/em><\/p>\n