Edition: BP 2025 (Ph. Eur. 11.6 update)<\/p>\n
Action and use<\/strong><\/p>\n Serotonin 5HT1 receptor agonist; treatment of migraine.<\/p>\n (4S)-4-[[3-[2-(Dimethylamino)ethyl]-1H-indol-5-yl]methyl]-1,3-oxazolidin-2-one.<\/p>\n Content<\/p>\n 97.5 per cent to 102.0 per cent (anhydrous substance).<\/p>\n White or almost white powder.<\/p>\n Slightly soluble or very slightly soluble in water, freely soluble in methanol, sparingly soluble in acetone.<\/p>\n Infrared absorption spectrophotometry (2.2.24).<\/p>\n Comparison\u00a0 zolmitriptan CRS.<\/p>\n Liquid chromatography (2.2.29).<\/p>\n Test solution Dissolve 25.0 mg of the substance to be examined in the mobile phase and dilute to 25.0 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 5 mg of zolmitriptan impurity A CRS in the mobile phase and dilute to 5.0 mL with the mobile phase. To 1.0 mL of the solution add 1.0 mL of the test solution and dilute to 10.0 mL with the mobile phase. Dilute 1.0 mL of this solution to 50.0 mL with the mobile phase.<\/p>\n Column:<\/p>\n \u2014 size: l = 0.25 m, \u00d8 = 4.6 mm;<\/p>\n \u2014 stationary phase: amylose derivative of silica gel for chiral separation R (5 \u00b5m);<\/p>\n \u2014 temperature: 35 \u00b0C.<\/p>\n Mobile phase diethylamine R, 2-propanol R, methanol R, heptane R (0.1:10:15:75 V\/V\/V\/V). Flow rate 1.0 mL\/min.<\/p>\n Detection\u00a0 Spectrophotometer at 285 nm.<\/p>\n Injection\u00a0 10 \u00b5L.<\/p>\n Run time\u00a0 Twice the retention time of zolmitriptan.<\/p>\n Relative retention\u00a0 With reference to zolmitriptan (retention time = about 7 min): impurity A = 0.7.<\/p>\n System suitability\u00a0 Reference solution (b):<\/p>\n \u2014 resolution: minimum 2.0 between the peaks due to impurity A and zolmitriptan.<\/p>\n Calculation of percentage content:<\/p>\n \u2014 for impurity A, use the concentration of zolmitriptan in reference solution (a).<\/p>\n Limit:<\/p>\n \u2014 impurity A: maximum 0.10 per cent.<\/p>\n Liquid chromatography (2.2.29).<\/p>\n Solvent mixture\u00a0 Mobile phase B, mobile phase A (10:90 V\/V).<\/p>\n Test solution (a) Dissolve 10.0 mg of the substance to be examined in the solvent mixture and dilute to 10.0 mL with the solvent mixture.<\/p>\n Test solution (b)\u00a0 Dilute 1.0 mL of test solution (a) to 5.0 mL with the solvent mixture.<\/p>\n Reference solution (a) Dilute 1.0 mL of test solution (a) to 100.0 mL with the solvent mixture. Dilute 1.0 mL of this soluti to 10.0 mL with the solvent mixture.<\/p>\n Reference solution (b) Dissolve 5 mg of zolmitriptan for system suitability CRS (containing impurities C, H and I) in the solvent mixture and dilute to 5.0 mL with the solvent mixture.<\/p>\n Reference solution (c) Dissolve 10.0 mg of zolmitriptan CRS in the solvent mixture and dilute to 10.0 mL with the solven mixture. Dilute 1.0 mL of the solution to 5.0 mL with the solvent mixture.<\/p>\n Column:<\/p>\n \u2014 size: l = 0.10 m, \u00d8 = 3.0 mm;<\/p>\n \u2014 stationary phase: end-capped solid core phenylhexylsilyl silica gel for chromatography R (2.7 \u00b5m);<\/p>\n \u2014 temperature: 20 \u00b0C.<\/p>\n Mobile phase A Dissolve 2.72 g of potassium dihydrogen phosphate R and 0.94 g of sodium hexanesulfonate R in wate for chromatography R, adjust to pH 2.0 with phosphoric acid R and dilute to 1000 mL with water for chromatography R;<\/p>\n Mobile phase B\u00a0 acetonitrile R1;<\/p>\n 0.5 – 4<\/p>\n 4 – 8<\/p>\n 8 – 9<\/p>\n 9 – 10<\/p>\n 10 – 12<\/p>\n 12 – 13<\/td>\n 90 \u2192 85<\/p>\n 85<\/p>\n 85 \u2192 80<\/p>\n 80<\/p>\n 80 \u2192 70<\/p>\n 70<\/td>\n 10 \u2192 15<\/p>\n 15<\/p>\n 15 \u2192 20<\/p>\n 20<\/p>\n 20 \u2192 30<\/p>\n 30<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n Flow rate\u00a0 0.8 mL\/min.<\/p>\n Detection\u00a0 Spectrophotometer at 210 nm.<\/p>\n Injection\u00a0 2 \u00b5L of test solution (a) and reference solutions (a) and (b).<\/p>\n Identification of impurities Use the chromatogram supplied with zolmitriptan for system suitability CRS and the chromatogram obtained with reference solution (b) to identify the peaks due to impurities C, H and I.<\/p>\n Relative retention\u00a0 With reference to zolmitriptan (retention time = about 5 min): impurity H = about 0.97; impurity I = about 1.1 ; impurity C = about 2.0.<\/p>\n System suitability\u00a0 Reference solution (b):<\/p>\n \u2014 peak-to-valley ratio: minimum 8, where Hp = height above the baseline of the peak due to impurity H and<\/p>\n Hv = height above the baseline of the lowest point of the curve separating this peak from the peak due to zolmitriptan minimum 1.5, where Hp = height above the baseline of the peak due to impurity I and Hv = height above the baseline of the lowest point of the curve separating this peak from the peak due to zolmitriptan.<\/p>\n Calculation of percentage contents:<\/p>\n \u2014 correction factor: multiply the peak area of impurity C by 2.0;<\/p>\n \u2014 for each impurity, use the concentration of zolmitriptan in reference solution (a).<\/p>\n Limits:<\/p>\n \u2014 impurity C: maximum 0.15 per cent;<\/p>\n \u2014 unspecified impurities: for each impurity, maximum 0.10 per cent;<\/p>\n \u2014 total: maximum 0.5 per cent;<\/p>\n \u2014 reporting threshold: 0.05 per cent.<\/p>\n Maximum 0.5 per cent, determined on 0.500 g.<\/p>\n Maximum 0.1 per cent, determined on 1.0 g.<\/p>\n Liquid chromatography (2.2.29) as described in the test for related substances with the following modifications.<\/p>\n Detection\u00a0 Spectrophotometer at 283 nm.<\/p>\n Injection\u00a0 2 \u00b5L of test solution (b) and reference solution (c).<\/p>\n Calculate the percentage content of C16<\/sub>H21<\/sub>N3<\/sub>O2<\/sub> taking into account the assigned content of zolmitriptan CRS.<\/p>\n Specified impurities\u00a0 A, C.<\/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 b the general monograph Substances for pharmaceutical use (2034). It is therefore not necessary to identify these impuriti for demonstration of compliance. See also 5.10. Control of impurities in substances for pharmaceutical use) B, D, E, F, H, I.<\/em><\/p>\n A. (4R)-4-[[3-[2-(dimethylamino)ethyl]-1H-indol-5-yl]methyl]-1,3-oxazolidin-2-one,<\/p>\n B. N,N-dimethyl-2-[5-[[(4S)-2-oxo-1,3-oxazolidin-4-yl]methyl]-1H-indol-3-yl]ethan-1-amine N-oxide,<\/p>\n C. (4S,4\u2032S)-4,4\u2032-[[4-(dimethylamino)butane-1,1-diyl]bis[[3-[2-(dimethylamino)ethyl]-1H-indole-2,5-diyl]methylene]]bis(1,3 oxazolidin-2-one),<\/p>\n D. (4S)-4-[[3-(2-aminoethyl)-1H-indol-5-yl]methyl]-1,3-oxazolidin-2-one,<\/p>\n E. (4S)-4-[(4-aminophenyl)methyl]-1,3-oxazolidin-2-one,<\/p>\n F. (2S)-2-amino-3-[3-[2-(dimethylamino)ethyl]-1H-indol-5-yl]propan-1-ol,<\/p>\n G. (4S)-4-[[3-[2-(methylamino)ethyl]-1H-indol-5-yl]methyl]-1,3-oxazolidin-2-one,<\/p>\n H. (4S)-4-[(2-methyl-1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indol-6-yl)methyl]-1,3-oxazolidin-2-one,<\/p>\n I. 3-[2-(dimethylamino)ethyl]-5-[[(4S)-2-oxo-1,3-oxazolidin-4-yl]methyl]-1H-indole-2-carboxylic acid.<\/p>\n","protected":false},"excerpt":{"rendered":" Edition: BP 2025 (Ph. Eur. 11.6 update) Action and use Serotonin 5HT1 receptor agonist; treatment of migraine. DEFINITION (4S)-4-[[3-[2-(Dimethylamino)ethyl]-1H-indol-5-yl]methyl]-1,3-oxazolidin-2-one. Content 97.5 per cent to 102.0 per cent (anhydrous substance). CHARACTERS Appearance White or almost white powder. Solubility Slightly soluble or very slightly soluble in water, freely soluble in methanol, sparingly soluble in acetone. IDENTIFICATION Infrared…<\/p>\n","protected":false},"author":5,"featured_media":31994,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-31993","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\/31993","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=31993"}],"version-history":[{"count":2,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/31993\/revisions"}],"predecessor-version":[{"id":31998,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/31993\/revisions\/31998"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/31994"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=31993"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=31993"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=31993"}],"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
Enantiomeric purity<\/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 – 0.5<\/p>\n 90<\/p>\n 10<\/p>\n Water (2.5.12)<\/h3>\n
Sulfated ash (2.4.14)<\/h3>\n
ASSAY<\/h2>\n
IMPURITIES<\/h2>\n