Edition: BP 2025 (Ph. Eur. 11.6 update)<\/p>\n
Action and use<\/strong><\/p>\n Non-benzodiazepine hypnotic.<\/p>\n Preparation <\/strong><\/p>\n Zopiclone Tablets<\/p>\n (5RS)-6-(5-Chloropyridin-2-yl)-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazin-5-yl 4-methylpiperazine-1-carboxylate.<\/p>\n Content<\/strong><\/p>\n 98.5 per cent to 100.5 per cent.<\/p>\n White or slightly yellowish powder.<\/p>\n Practically insoluble in water, freely soluble in methylene chloride, sparingly soluble in acetone, practically insoluble in ethanol (96 per cent). It dissolves in dilute mineral acids.<\/p>\n First identification: B.<\/em><\/p>\n Second identification: A, C.<\/em><\/p>\n A. Ultraviolet and visible absorption spectrophotometry (2.2.25).<\/p>\n Test solution Dissolve 50.0 mg in a 3.5 g\/L solution of hydrochloric acid R and dilute to 100.0 mL with the same solvent. Dilute 2.0 mL of this solution to 100.0 mL with a 3.5 g\/L solution of hydrochloric acid R.<\/p>\n Spectral range\u00a0 220-350 nm.<\/p>\n Absorption maximum\u00a0 303 nm.<\/p>\n Specific absorbance at the absorption maximum\u00a0 340 to 380.<\/p>\n B. Infrared absorption spectrophotometry (2.2.24).<\/p>\n Comparison\u00a0 zopiclone CRS.<\/p>\n C. Thin-layer chromatography (2.2.27).<\/p>\n Test solution Dissolve 10 mg of the substance to be examined in methylene chloride R and dilute to 10 mL with the same solvent.<\/p>\n Reference solution\u00a0 Dissolve 10 mg of zopiclone CRS in methylene chloride R and dilute to 10 mL with the same solvent.<\/p>\n Plate\u00a0 TLC silica gel GF254 plate R.<\/p>\n Mobile phase triethylamine R, acetone R, ethyl acetate R (2:50:50 V\/V\/V). Application 10 \u00b5L.<\/p>\n Development\u00a0 Over 2\/3 of the plate.<\/p>\n Drying\u00a0 In air.<\/p>\n Detection\u00a0 Examine in ultraviolet light at 254 nm.<\/p>\n Results The principal spot in the chromatogram obtained with the test solution is similar in position and size to the principal spot in the chromatogram obtained with the reference solution.<\/p>\n Dissolve 1.0 g in dimethylformamide R and dilute to 20.0 mL with the same solvent.<\/p>\n Solution S is not more opalescent than reference suspension II (2.2.1) and not more intensely coloured than intensity 5 of the range of reference solutions of the most appropriate colour (2.2.2, Method II).<\/p>\n -0.05\u00b0 to + 0.05\u00b0.<\/p>\n Dilute 10.0 mL of solution S to 50.0 mL with dimethylformamide R.<\/p>\n Liquid chromatography (2.2.29). Prepare the solutions immediately before use.<\/p>\n Test solution Dissolve 40.0 mg of the substance to be examined in the mobile phase and dilute to 10.0 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 4 mg of zopiclone oxide CRS (impurity A) in the mobile phase and dilute to 10 mL with the mobile phase. To 5 mL of the solution add 0.5 mL of the test solution and dilute to 50 mL with the mobile phase.<\/p>\n Reference solution (c) Dissolve 2.0 mg of zopiclone impurity B CRS in the mobile phase and dilute to 5.0 mL with the mobile phase. Dilute 1.0 mL of the solution to 100.0 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: end-capped octadecylsilyl silica gel for chromatography R (5 \u00b5m);<\/p>\n \u2014 temperature: 30 \u00b0C.<\/p>\n Mobile phase Mix 38 volumes of acetonitrile R and 62 volumes of a solution containing 8.1 g\/L of sodium laurilsulfate R and 1.6 g\/L of sodium dihydrogen phosphate R, previously adjusted to pH 3.5 with a 10 per cent V\/V solution of phosphoric acid R or a 200 g\/L solution of sodium hydroxide R.<\/p>\n Flow rate\u00a0 1.5 mL\/min.<\/p>\n Detection\u00a0 Spectrophotometer at 303 nm.<\/p>\n Injection\u00a0 20 \u00b5L.<\/p>\n Run time\u00a0 1.5 times the retention time of zopiclone.<\/p>\n Identification of impurities Use the chromatogram obtained with reference solution (c) to identify the peak due to impurity B; use the chromatogram obtained with reference solution (b) to identify the peak due to impurity A.<\/p>\n Retention time\u00a0 Zopiclone = 27 min to 31 min; if necessary, adjust the concentration of acetonitrile in the mobile phase.<\/p>\n Relative retention\u00a0 With reference to zopiclone: impurity B = about 0.1; impurity A = about 0.9.<\/p>\n System suitability\u00a0 Reference solution (b):<\/p>\n \u2014 resolution: minimum 3.0 between the peaks due to impurity A and zopiclone; if necessary, adjust the mobile phase to an apparent pH of 4.0 with a 10 per cent V\/V solution of phosphoric acid R or a 200 g\/L solution of sodium hydroxide R.<\/p>\n Calculation of percentage contents:<\/p>\n \u2014 for impurity B, use the concentration of impurity B in reference solution (c);<\/p>\n \u2014 for impurities other than B, use the concentration of zopiclone in reference solution (a).<\/p>\n Limits:<\/p>\n \u2014 impurity B: maximum 0.2 per cent;<\/p>\n \u2014 unspecified impurities: for each impurity, maximum 0.10 per cent;<\/p>\n \u2014 total (excluding impurity B): maximum 0.2 per cent;<\/p>\n \u2014 reporting threshold: 0.05 per cent.<\/p>\n Gas chromatography (2.2.28): maximum 0.7 per cent.<\/p>\n Internal standard solution Dissolve 0.350 g of ethanol R1 in dimethyl sulfoxide R and dilute to 20.0 mL with dimethyl sulfoxide R. Dilute 10.0 mL of the solution to 500.0 mL with dimethyl sulfoxide R.<\/p>\n Test solution\u00a0 Dissolve 50 mg of the substance to be examined in 1 mL of the internal standard solution.<\/p>\n Reference solution Dissolve 17.5 mg of 2-propanol R in the internal standard solution and dilute to 50.0 mL with the same solution.<\/p>\n Column:<\/p>\n \u2014 material: fused silica;<\/p>\n \u2014 size: l = 30 m, \u00d8 = 0.32 mm;<\/p>\n \u2014 stationary phase: cyanopropyl(3)phenyl(3)methyl(94)polysiloxane R (film thickness 1.8 \u00b5m).<\/p>\n Carrier gas helium for chromatography R. Flow rate 2.2 mL\/min.<\/p>\n Split ratio\u00a0 1:5.<\/p>\n Static head-space conditions that may be used:<\/p>\n \u2014 equilibration temperature: 110 \u00b0C;<\/p>\n \u2014 equilibration time: 10 min;<\/p>\n \u2014 transfer-line temperature: 120 \u00b0C.<\/p>\n Temperature:<\/p>\n Detection\u00a0 Flame ionisation.<\/p>\n Injection\u00a0 1 mL.<\/p>\n System suitability\u00a0 Reference solution:<\/p>\n \u2014 resolution: minimum 3.0 between the peaks due to ethanol and 2-propanol.<\/p>\n Maximum 0.1 per cent, determined on 1.0 g.<\/p>\n Dissolve 0.300 g in a mixture of 10 mL of anhydrous acetic acid R and 40 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 38.88 mg of C17<\/sub>H17<\/sub>ClN6<\/sub>O3<\/sub>.<\/p>\n Protected from light.<\/p>\n Specified impurities\u00a0 B.<\/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) A, C.<\/em><\/p>\n A. 4-[[[(5RS)-6-(5-chloropyridin-2-yl)-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazin-5-yl]oxy]carbonyl]-1-methylpiperazine 1- oxide (zopiclone oxide),<\/p>\n B. (7RS)-6-(5-chloropyridin-2-yl)-7-hydroxy-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazin-5-one,<\/p>\n C. 6-(5-chloropyridin-2-yl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazin-5-one.<\/p>\n","protected":false},"excerpt":{"rendered":" Edition: BP 2025 (Ph. Eur. 11.6 update) Action and use Non-benzodiazepine hypnotic. Preparation Zopiclone Tablets DEFINITION (5RS)-6-(5-Chloropyridin-2-yl)-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazin-5-yl 4-methylpiperazine-1-carboxylate. Content 98.5 per cent to 100.5 per cent. CHARACTERS Appearance White or slightly yellowish powder. Solubility Practically insoluble in water, freely soluble in methylene chloride, sparingly soluble in acetone, practically insoluble in ethanol (96 per cent). It…<\/p>\n","protected":false},"author":5,"featured_media":32010,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-32009","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\/32009","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=32009"}],"version-history":[{"count":2,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/32009\/revisions"}],"predecessor-version":[{"id":32017,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/32009\/revisions\/32017"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/32010"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=32009"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=32009"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=32009"}],"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
Solution S<\/h3>\n
Appearance of solution<\/h3>\n
Optical rotation (2.2.7)<\/h3>\n
Related substances<\/h3>\n
2-Propanol<\/h3>\n
\n\n
\n <\/td>\n Time (min)<\/strong><\/td>\n Temperature (\u00b0C)<\/strong><\/td>\n<\/tr>\n \n Column<\/td>\n 0 – 5<\/td>\n 40<\/td>\n<\/tr>\n \n 5 – 15<\/td>\n 240<\/td>\n<\/tr>\n \n 15 – 20<\/td>\n 240<\/td>\n<\/tr>\n \n Injection port<\/td>\n 225<\/td>\n<\/tr>\n \n Detector<\/td>\n 250<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n Sulfated ash (2.4.14)<\/h3>\n
ASSAY<\/h2>\n
STORAGE<\/h2>\n
IMPURITIES<\/h2>\n