Edition: BP 2025 (Ph. Eur. 11.6 update)<\/p>\n
2-Ethoxy-4-[2-[[(1S)-3-methyl-1-[2-(piperidin-1-yl)phenyl]butyl]amino]-2-oxoethyl]benzoic acid.<\/p>\n
Content<\/strong><\/p>\n 99.0 per cent to 101.0 per cent (dried substance).<\/p>\n White or almost white powder.<\/p>\n Practically insoluble in water, freely soluble in methanol and in methylene chloride. It shows polymorphism (5.9).<\/p>\n A. Specific optical rotation (2.2.7): + 6.3 to + 7.7.<\/p>\n Dissolve 1.00 g in methanol R and dilute to 20.0 mL with the same solvent.<\/p>\n B. Infrared absorption spectrophotometry (2.2.24).<\/p>\n Comparison\u00a0 repaglinide CRS.<\/p>\n If the spectra obtained in the solid state show differences, dissolve the substance to be examined and the reference substance separately in anhydrous ethanol R, evaporate to dryness and record new spectra using the residues.<\/p>\n Liquid chromatography (2.2.29). Prepare the solutions in amber flasks and vials.<\/p>\n Test solution Dissolve 10.0 mg of the substance to be examined in methanol R and dilute to 10.0 mL with the same solvent.<\/p>\n Reference solution (a) Dissolve 5.0 mg of repaglinide impurity E CRS in methanol R and dilute to 50.0 mL with the same of solvent.<\/p>\n Reference solution (b)\u00a0 Dilute 2.0 mL of reference solution (a) to 100.0 mL with methanol R.<\/p>\n Reference solution (c)\u00a0 Mix 1.0 mL of the test solution and 10 mL of reference solution (a) and dilute to 50.0 mL with methanol R. Column:<\/p>\n \u2014 size: l = 0.1 m, \u00d8 = 4.0 mm,<\/p>\n \u2014 stationary phase: silica gel AGP for chiral chromatography R (5 \u00b5m).<\/p>\n Mobile phase:<\/p>\n \u2014 mobile phase A: 1.0 g\/L solution of potassium dihydrogen phosphate R adjusted to pH 4.7 with dilute sodium hydroxide solution R;<\/p>\n \u2014 mobile phase B: acetonitrile R;<\/p>\n Equilibration after installation of the column for use\u00a0 Using water R, slowly increase the flow rate from 0.2 mL\/min to 0.5 mL\/min. Maintain the flow rate at 0.5 mL\/min for 5 min. The column must be washed for 1 h at a flow rate of 1 mL\/min with water R and for 1 h with the mobile phase at the initial composition prior to the 1st analysis.<\/p>\n Flow rate\u00a0 1.0 mL\/min.<\/p>\n Detection\u00a0 Spectrophotometer at 240 nm.<\/p>\n Injection 10 \u00b5L of the test solution and reference solutions (b) and (c). Retention time Repaglinide = about 3.3 min; impurity E = about 5.0 min. System suitability<\/p>\n Reference solution (c):<\/p>\n \u2014 resolution: minimum 1.5 between the peaks due to repaglinide and impurity E.<\/p>\n Limit:<\/p>\n \u2014 impurity E: not more than the area of the principal peak in the chromatogram obtained with reference solution (b) (0.2 per cent).<\/p>\n Liquid chromatography (2.2.29).<\/p>\n Test solution Dissolve 30.0 mg of the substance to be examined in acetonitrile R and dilute to 10.0 mL with the same solvent.<\/p>\n Reference solution (a)\u00a0 Dilute 5.0 mL of the test solution to 100.0 mL with acetonitrile R. Dilute 2.0 mL of this solution to 100.0 mL with acetonitrile R.<\/p>\n Reference solution (b) With the aid of an ultrasonic bath, dissolve the contents of 1 vial of repaglinide for system suitability CRS in 2.0 mL of acetonitrile R.<\/p>\n Column:<\/p>\n \u2014 size: l = 0.15 m, \u00d8 = 4.6 mm,<\/p>\n \u2014 stationary phase: silica gel for chromatography , alkyl-bonded for use with highly aqueous mobile phases R (5 \u00b5m),<\/p>\n \u2014 temperature: 45 \u00b0C.<\/p>\n Mobile phase:<\/p>\n \u2014 mobile phase A: 4.0 g\/L solution of potassium dihydrogen phosphate R adjusted to pH 3.2 with dilute phosphoric acid R;<\/p>\n \u2014 mobile phase B: mobile phase A, acetonitrile R (300:700 V\/V);<\/p>\n Flow rate\u00a0 1.5 mL\/min.<\/p>\n Detection\u00a0 Spectrophotometer at 240 nm.<\/p>\n Injection\u00a0 10 \u00b5L.<\/p>\n Relative retention With reference to repaglinide (retention time = about 10 min): impurity A = about 0.2; impurity B = about 0.3; impurity C = about 0.4; impurity D = about 1.5.<\/p>\n System suitability\u00a0 Reference solution (b):<\/p>\n \u2014 resolution: minimum 5.0 between the peaks due to impurity B and impurity C,<\/p>\n \u2014 the chromatogram obtained is similar to the chromatogram supplied with repaglinide for system suitability CRS. Limits:<\/p>\n \u2014 correction factors: for the calculation of contents, multiply the peak areas of the following impurities by the corresponding correction factor: impurity A = 0.6; impurity B = 0.7; impurity C = 3.1;<\/p>\n \u2014 impurities A, B, C, D: for each impurity, not more than the area of the principal peak in the chromatogram obtained with reference solution (a) (0.1 per cent);<\/p>\n \u2014 any other impurity: for each impurity, not more than the area of the principal peak in the chromatogram obtained with reference solution (a) (0.1 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 0.320 g in 10 mL methanol R and add 60 mL of anhydrous acetic acid 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 45.26 mg of C27<\/sub>H36<\/sub>N2<\/sub>O4<\/sub>.<\/p>\n Protected from light.<\/p>\n Specified impurities\u00a0 A, B, C, D, E.<\/p>\n A. 4-(carboxymethyl)-2-ethoxybenzoic acid,<\/p>\n B. [3-ethoxy-4-(ethoxycarbonyl)phenyl]acetic acid,<\/p>\n C. (1S)-3-methyl-1-[2-(piperidin-1-yl)phenyl]butan-1-amine,<\/p>\n D. ethyl 2-ethoxy-4-[2-[[(1S)-3-methyl-1-[2-(piperidin-1-yl)phenyl]butyl]amino]-2-oxoethyl]benzoate,<\/p>\n E. 2-ethoxy-4-[2-[[(1R)-3-methyl-1-[2-(piperidin-1-yl)phenyl]butyl]amino]-2-oxoethyl]benzoic acid<\/p>\n","protected":false},"excerpt":{"rendered":" Edition: BP 2025 (Ph. Eur. 11.6 update) DEFINITION 2-Ethoxy-4-[2-[[(1S)-3-methyl-1-[2-(piperidin-1-yl)phenyl]butyl]amino]-2-oxoethyl]benzoic acid. Content 99.0 per cent to 101.0 per cent (dried substance). CHARACTERS Appearance White or almost white powder. Solubility Practically insoluble in water, freely soluble in methanol and in methylene chloride. It shows polymorphism (5.9). IDENTIFICATION A. Specific optical rotation (2.2.7): + 6.3 to + 7.7….<\/p>\n","protected":false},"author":5,"featured_media":29563,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-29561","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\/29561","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=29561"}],"version-history":[{"count":2,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/29561\/revisions"}],"predecessor-version":[{"id":29574,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/29561\/revisions\/29574"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/29563"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=29561"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=29561"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=29561"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}CHARACTERS<\/h2>\n
Appearance<\/h3>\n
Solubility<\/h3>\n
IDENTIFICATION<\/h2>\n
TESTS<\/h2>\n
Enantiomeric purity<\/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 – 4<\/td>\n 80 \u2192 60<\/td>\n 20 \u2192 40<\/td>\n<\/tr>\n \n 4 – 6<\/td>\n 60<\/td>\n 40<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\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 – 20<\/td>\n 50 \u2192 7<\/td>\n 50 \u2192 93<\/td>\n<\/tr>\n \n 20 – 30<\/td>\n 7<\/td>\n 93<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n ASSAY<\/h2>\n
STORAGE<\/h2>\n
IMPURITIES<\/h2>\n