Edition: BP 2025 (Ph. Eur. 11.6 update)<\/p>\n
Action and use <\/strong><\/p>\n Cholinesterase inhibitor. Preparation Neostigmine Tablets<\/p>\n Ph Eur<\/p>\n DEFINITION<\/p>\n 3-[(Dimethylcarbamoyl)oxy]-N,N,N-trimethylanilinium bromide.<\/p>\n Content<\/strong><\/p>\n 98.5 per cent to 101.0 per cent (dried substance).<\/p>\n White or almost white, crystalline powder or colourless crystals, hygroscopic.<\/p>\n Very soluble in water, freely soluble in ethanol (96 per cent).<\/p>\n First identification: B, D. Second identification: A, C, D.<\/p>\n A. Ultraviolet and visible absorption spectrophotometry (2.2.25).<\/p>\n Test solution\u00a0 Dissolve 20 mg in 0.5 M sulfuric acid and dilute to 100 mL with the same acid.<\/p>\n Spectral range\u00a0 230-350 nm.<\/p>\n Absorption maxima\u00a0 260 nm and 266 nm.<\/p>\n Specific absorbance at the absorption maxima:<\/p>\n \u2014 260 nm: about 16;<\/p>\n \u2014 266 nm: about 14.<\/p>\n B. Infrared absorption spectrophotometry (2.2.24).<\/p>\n Comparison\u00a0 neostigmine bromide CRS.<\/p>\n C. To 50 mg add 0.4 g of potassium hydroxide R and 2 mL of ethanol (96 per cent) R and heat on a water- bath for 3 min, replacing the evaporated ethanol (96 per cent). Cool and add 2 mL of water R and 2 mL of diazobenzenesulfonic acid solution R1. An orange-red colour develops.<\/p>\n D. It gives reaction (a) of bromides (2.3.1).<\/p>\n Dissolve 2.5 g in distilled water R and dilute to 50 mL with the same solvent.<\/p>\n Solution S is clear (2.2.1) and colourless (2.2.2, Method II).<\/p>\n Liquid chromatography (2.2.29).<\/p>\n Test solution\u00a0 Dissolve 50 mg of the substance to be examined in the mobile phase and dilute to 50.0 mL with the mobile phase.<\/p>\n Reference solution (a)\u00a0 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)\u00a0 Dissolve 4 mg of 3-dimethylaminophenol R (impurity B) in 50 mL of the mobile phase. Dilute 1 mL of the solution to 200 mL with the mobile phase.<\/p>\n Reference solution (c)\u00a0 Dissolve the contents of a vial of neostigmine impurity A CRS in 1 mL of reference solution (b).<\/p>\n Reference solution (d)\u00a0 Mix 1 mL of the mobile phase and 1 mL of reference solution (a).<\/p>\n Column:<\/p>\n \u2014 size: l = 0.25 m, \u00d8 = 4.0 mm;<\/p>\n \u2014 stationary phase: base-deactivated octylsilyl silica gel for chromatography R (5 \u00b5m);<\/p>\n \u2014 temperature: 30 \u00b0C.<\/p>\n Mobile phase\u00a0 To 710 mL of a 3.6 g\/L solution of sodium dihydrogen phosphate R previously adjusted to pH 3.2 with phosphoric acid R, add 4.3 g of sodium dodecyl sulfate R and 290 mL of acetonitrile for chromatography R.<\/p>\n Flow rate\u00a0 1.6 mL\/min.<\/p>\n Detection\u00a0 Spectrophotometer at 220 nm.<\/p>\n Injection\u00a0 50 \u00b5L of the test solution and reference solutions (a), (c) and (d).<\/p>\n Run time\u00a0 Twice the retention time of neostigmine.<\/p>\n Identification of impurities\u00a0 Use the chromatogram obtained with reference solution (c) to identify the peaks due to impurities A and B.<\/p>\n Relative retention\u00a0 With reference to neostigmine (retention time = about 20 min): impurity B = about 0.56; impurity A = about 0.61.<\/p>\n System suitability:<\/p>\n \u2014 resolution: minimum 1.5 between the peaks due to impurities B and A in the chromatogram obtained with reference solution (c);<\/p>\n \u2014 signal-to-noise ratio: minimum 25 for the principal peak in the chromatogram obtained with reference solution (d).<\/p>\n Calculation of percentage contents:<\/p>\n \u2014 for each impurity, use the concentration of neostigmine bromide in reference solution (a);<\/p>\n \u2014 correction factor: multiply the peak area of impurity B by 0.5.<\/p>\n Limits:<\/p>\n \u2014 impurity B: maximum 0.01 per cent;<\/p>\n \u2014 unspecified impurities: for each impurity, maximum 0.10 per cent;<\/p>\n \u2014 total: maximum 0.3 per cent;<\/p>\n \u2014 reporting threshold: 0.05 per cent; disregard the peak due to impurity B.<\/p>\n Maximum 200 ppm, determined on solution S.<\/p>\n Loss on drying (2.2.32)<\/strong><\/p>\n Maximum 1.0 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 ASSAY<\/h2>\n Dissolve 0.225 g in 2 mL of formic acid R. Add 50 mL of acetic anhydride R. Titrate with 0.1 M perchloric acid, determining the end-point potentiometrically (2.2.20). In an airtight container, 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.<\/em><\/p>\n Control of impurities in substances for pharmaceutical use)\u00a0 A, C.<\/em><\/p>\n A. 3-hydroxy-N,N,N-trimethylanilinium,<\/p>\n B. 3-(dimethylamino)phenol,<\/p>\n C. 3-(dimethylamino)phenyl dimethylcarbamate.<\/p>\n Ph Eur<\/p>\n","protected":false},"excerpt":{"rendered":" Edition: BP 2025 (Ph. Eur. 11.6 update) Action and use Cholinesterase inhibitor. Preparation Neostigmine Tablets Ph Eur DEFINITION 3-[(Dimethylcarbamoyl)oxy]-N,N,N-trimethylanilinium bromide. Content 98.5 per cent to 101.0 per cent (dried substance). CHARACTERS Appearance White or almost white, crystalline powder or colourless crystals, hygroscopic. Solubility Very soluble in water, freely soluble in ethanol (96 per cent). IDENTIFICATION…<\/p>\n","protected":false},"author":5,"featured_media":25897,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-25896","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\/25896","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=25896"}],"version-history":[{"count":2,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/25896\/revisions"}],"predecessor-version":[{"id":25900,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/25896\/revisions\/25900"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/25897"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=25896"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=25896"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=25896"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}
\nCHARACTERS<\/h2>\n
Appearance<\/h3>\n
Solubility<\/h3>\n
IDENTIFICATION<\/h2>\n
TESTS<\/h2>\n
Solution S<\/h3>\n
Appearance of solution<\/h3>\n
Related substances<\/h3>\n
Sulfates (2.4.13)<\/h3>\n
Maximum 0.1 per cent, determined on 1.0 g.<\/p>\n
\n1 mL of 0.1 M perchloric acid is equivalent to 30.32 mg of C12H19BrN2O2.<\/p>\nSTORAGE<\/h2>\n
IMPURITIES<\/h2>\n
\n