Edition: BP 2025 (Ph. Eur. 11.6 update)<\/p>\n
Action and use<\/strong><\/p>\n Neuraminidase inhibitor; treatment and prophylaxis of influenza.<\/p>\n Preparation<\/strong><\/p>\n Zanamivir Inhalation Powder, pre-metered Ph Eur<\/p>\n (2R,3R,4S)-3-Acetamido-4-carbamimidamido-2-[(1R,2R)-1,2,3-trihydroxypropyl]-3,4-dihydro-2H-pyran-6-carboxylic acid hydrate.<\/p>\n Content<\/strong><\/p>\n 97.0 per cent to 102.0 per cent (dried substance).<\/p>\n It contains a variable quantity of water.<\/p>\n White or almost white, slightly hygroscopic powder.<\/p>\n IDENTIFICATION<\/h2>\n A. Specific optical rotation (see Tests).<\/p>\n B. Infrared absorption spectrophotometry (2.2.24).<\/p>\n Comparison\u00a0 zanamivir hydrate CRS.<\/p>\n + 36.0 to + 38.5 (dried substance).<\/p>\n Dissolve 0.250 g in 25.0 mL of water R; sonicate until dissolution is complete.<\/p>\n Liquid chromatography (2.2.29).<\/p>\n Test solution (a)\u00a0 Dissolve 23.0 mg of the substance to be examined in 20 mL of water R and dilute to 50.0 mL with acetonitrile R1.<\/p>\n Test solution (b)\u00a0 Dilute 5.0 mL of test solution (a) to 50.0 mL with the mobile phase.<\/p>\n Reference solution (a)\u00a0 Dissolve 23.0 mg of zanamivir for assay CRS in 20 mL of water R and dilute to 50.0 mL with acetonitrile R1. Dilute 5.0 mL of the solution to 50.0 mL with the mobile phase.<\/p>\n Reference solution (b) Dissolve 5 mg of zanamivir for system suitability CRS (containing impurities A, B, C and E) in 6 mL of water R and dilute to 10 mL with acetonitrile R1.<\/p>\n Reference solution (c) Dilute 1.0 mL of test solution (a) 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 (d) Dissolve 3.0 mg of zanamivir impurity F CRS in the mobile phase and dilute to 100.0 mL with the mobile phase.<\/p>\n Reference solution (e) Dilute 1.0 mL of reference solution (d) to 100.0 mL with the mobile phase. Dilute 3.0 mL of this solution to 20.0 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: amino alkyl vinyl polymer for chromatography R (5 \u00b5m);<\/p>\n \u2014 temperature: 30 \u00b0C.<\/p>\n Mobile phase\u00a0 0.7 g\/L solution of sulfuric acid R previously adjusted to pH 5.5 with dilute ammonia R3, acetonitrile R1 (40:60 V\/V).<\/p>\n Flow rate\u00a0 1.5 mL\/min.<\/p>\n Detection\u00a0 Spectrophotometer at 234 nm.<\/p>\n Preconditioning of the column Prior to first use, rinse with a 0.7 g\/L solution of ammonium sulfate R at 1.5 mL\/min at 30 \u00b0C for about 1 h; prior to each use, rinse with the mobile phase for at least 8 h.<\/p>\n Injection\u00a0 20 \u00b5L of test solution (a) and reference solutions (b), (c) and (e).<\/p>\n Run time\u00a0 3 times the retention time of zanamivir.<\/p>\n Identification of impurities Use the chromatogram supplied with zanamivir for system suitability CRS and the chromatogram obtained with reference solution (b) to identify the peaks due to impurities A, B, C and E; use the chromatogram obtained with reference solution (e) to identify the peak due to impurity F.<\/p>\n Relative retention With reference to zanamivir (retention time = about 9 min): impurity F = about 0.3; impurity B = about 0.6; impurity C = about 0.75; impurity E = about 0.8; impurity A = about 2.6.<\/p>\n System suitability:<\/p>\n \u2014 signal-to-noise ratio: minimum 10 for the principal peak in the chromatogram obtained with reference solution (e);<\/p>\n \u2014 peak-to-valley ratio: minimum 2.5, where Hp = height above the baseline of the peak due to impurity E and<\/p>\n Hv = height above the baseline of the lowest point of the curve separating this peak from the peak due to impurity C in the chromatogram obtained with reference solution (b).<\/p>\n Calculation of percentage contents:<\/p>\n \u2014 for impurity F, use the concentration of impurity F in reference solution (e);<\/p>\n \u2014 for impurities other than F, use the concentration of zanamivir hydrate in reference solution (c).<\/p>\n Limits:<\/p>\n \u2014 impurity A: maximum 0.5 per cent;<\/p>\n \u2014 impurity B: maximum 0.3 per cent;<\/p>\n \u2014 impurity C: maximum 0.2 per cent;<\/p>\n \u2014 impurity F: maximum 0.01 per cent;<\/p>\n \u2014 unspecified impurities: for each impurity, maximum 0.10 per cent;<\/p>\n \u2014 total: maximum 1.2 per cent;<\/p>\n \u2014 reporting threshold: 0.05 per cent, except for impurity F.<\/p>\n 4.0 per cent to 9.0 per cent, determined on 1.000 g by drying in vacuo at 105 \u00b0C.<\/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 modification.<\/p>\n Injection\u00a0 Test solution (b) and reference solution (a).<\/p>\n Calculate the percentage content of C12<\/sub>H20<\/sub>N4<\/sub>O7<\/sub> taking into account the assigned content of zanamivir for assay CRS.<\/p>\n In an airtight container, protected from light.<\/p>\n Specified impurities\u00a0 A, B, C, F.<\/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) D, E, H.<\/em><\/p>\n A. (2R,3R,4S)-3-acetamido-2-[(1R,2R)-3-[[[(2R,3R,4S)-3-acetamido-6-carboxy-2-[(1R,2R)-1,2,3-trihydroxypropyl]-3,4-\u00a0 dihydro-2H-pyran-4-yl]carbamoyl]oxy]-1,2-dihydroxypropyl]-4-carbamimidamido-3,4-dihydro-2H-pyran-6-carboxylic acid,<\/p>\n B. unknown structure,<\/p>\n C. (2R,3R,4S)-3-acetamido-4-amino-2-[(1R,2R)-1,2,3-trihydroxypropyl]-3,4-dihydro-2H-pyran-6-carboxylic acid,<\/p>\n D. (2R,3R,4S)-3-acetamido-4-(carbamoylamino)-2-[(1R,2R)-1,2,3-trihydroxypropyl]-3,4-dihydro-2H-pyran-6-carboxylic acid,<\/p>\n E. (2R,3R,4S)-3-acetamido-4-(N\u2032-carbamimidoylcarbamimidamido)-2-[(1R,2R)-1,2,3-trihydroxypropyl]-3,4-dihydro-2H- pyran-6-carboxylic acid,<\/p>\n F. 1H-pyrazole-1-carboximidamide,<\/p>\n H. (2R,3R,4R)-3-acetamido-4-carbamimidamido-2-[(1R,2R)-1,2,3-trihydroxypropyl]-3,4-dihydro-2H-pyran-6-carboxylic acid.<\/p>\n","protected":false},"excerpt":{"rendered":" Edition: BP 2025 (Ph. Eur. 11.6 update) Action and use Neuraminidase inhibitor; treatment and prophylaxis of influenza. Preparation Zanamivir Inhalation Powder, pre-metered Ph Eur DEFINITION (2R,3R,4S)-3-Acetamido-4-carbamimidamido-2-[(1R,2R)-1,2,3-trihydroxypropyl]-3,4-dihydro-2H-pyran-6-carboxylic acid hydrate. Content 97.0 per cent to 102.0 per cent (dried substance). It contains a variable quantity of water. CHARACTERS Appearance White or almost white, slightly hygroscopic powder. Solubility…<\/p>\n","protected":false},"author":5,"featured_media":31858,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-31857","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\/31857","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=31857"}],"version-history":[{"count":2,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/31857\/revisions"}],"predecessor-version":[{"id":31863,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/31857\/revisions\/31863"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/31858"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=31857"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=31857"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=31857"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}DEFINITION<\/h2>\n
CHARACTERS<\/h2>\n
Appearance<\/h3>\n
Solubility<\/h3>\n
Slightly soluble in water, practically insoluble in ethanol (96 per cent) and in methylene chloride.<\/p>\n
TESTS<\/h2>\n
Specific optical rotation (2.2.7)<\/h3>\n
Related substances<\/h3>\n
Loss on drying (2.2.32)<\/h3>\n
Sulfated ash (2.4.14)<\/h3>\n
ASSAY<\/h2>\n
STORAGE<\/h2>\n
IMPURITIES<\/h2>\n