Edition: BP 2025 (Ph. Eur. 11.6 update)<\/p>\n
Action and use <\/strong><\/p>\n Antiprotozoal (malaria).<\/p>\n Preparations<\/strong><\/p>\n Quinine Sulfate Oral Suspension<\/p>\n Quinine Sulfate Tablets<\/p>\n Alkaloid monosulfates, expressed as bis[(R)-[(2S,4S,5R)-5-ethenyl-1-azabicyclo[2.2.2]oct-2-yl](6-methoxyquinolin-4- yl)methanol] sulfate dihydrate.<\/p>\n Content<\/strong><\/p>\n 99.0 per cent to 101.0 per cent (dried substance).<\/p>\n White or almost white, crystalline powder or fine, colourless needles.<\/p>\n Slightly soluble in water, sparingly soluble in boiling water and in ethanol (96 per cent).<\/p>\n A. Thin-layer chromatography (2.2.27).<\/p>\n Test solution\u00a0 Dissolve 0.10 g of the substance to be examined in methanol R and dilute to 10 mL with the same solvent.<\/p>\n Reference solution\u00a0 Dissolve 0.10 g of quinine sulfate CRS in methanol R and dilute to 10 mL with the same solvent.<\/p>\n Plate\u00a0 TLC silica gel G plate R.<\/p>\n Mobile phase diethylamine R, ether R, toluene R (10:24:40 V\/V\/V). Application 5 \u00b5L.<\/p>\n Development\u00a0 Twice over a path of 15 cm; dry in a current of air for 15 min between the 2 developments.<\/p>\n Drying\u00a0 At 105 \u00b0C for 30 min and allow to cool.<\/p>\n Detection\u00a0 Spray with iodoplatinate reagent R.<\/p>\n Results The principal spot in the chromatogram obtained with the test solution is similar in position, colour and size to the principal spot in the chromatogram obtained with the reference solution.<\/p>\n B. Dissolve about 5 mg in 5 mL of water R. Add 0.2 mL of bromine water R and 1 mL of dilute ammonia R2. A green colour develops.<\/p>\n C. Dissolve 0.1 g in 3 mL of dilute sulfuric acid R and dilute to 100 mL with water R. When examined in ultraviolet light at 366 nm, an intense blue fluorescence appears which disappears almost completely on the addition of 1 mL of hydrochloric acid R.<\/p>\n D. Dissolve about 45 mg in 5 mL of dilute hydrochloric acid R. The solution gives reaction (a) of sulfates (2.3.1).<\/p>\n E. pH (see Tests).<\/p>\n Dissolve 0.500 g in 0.1 M hydrochloric acid and dilute to 25.0 mL with the same acid.<\/p>\n Solution S is clear (2.2.1) and not more intensely coloured than reference solution GY6 (2.2.2, Method II).<\/p>\n pH (2.2.3)<\/strong><\/p>\n 5.7 to 6.6 for a 10 g\/L suspension in water R.<\/p>\n Specific optical rotation (2.2.7)<\/strong><\/p>\n -237 to -245 (dried substance), determined on solution S.<\/p>\n Liquid chromatography (2.2.29): use the normalisation procedure.<\/p>\n Test solution Dissolve 20 mg of the substance to be examined in 5 mL of the mobile phase, with gentle heating if necessary, and dilute to 10 mL with the mobile phase.<\/p>\n Reference solution (a) Dissolve 20 mg of quinine sulfate CRS in 5 mL of the mobile phase, with gentle heating if necessary, and dilute to 10 mL with the mobile phase.<\/p>\n Reference solution (b) Dissolve 20 mg of quinidine sulfate CRS (impurity A) in 5 mL of the mobile phase, with gentle heating if necessary, and dilute to 10 mL with the mobile phase.<\/p>\n Reference solution (c)\u00a0 To 1 mL of reference solution (a) add 1 mL of reference solution (b).<\/p>\n Reference solution (d) Dilute 1.0 mL of reference solution (a) 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 Reference solution (e)\u00a0 Dissolve 10 mg of thiourea R in the mobile phase and dilute to 10 mL with the mobile phase.<\/p>\n Column:<\/p>\n \u2014 size: l = 0.15-0.25 m, \u00d8 = 4.6 mm;<\/p>\n \u2014 stationary phase: octadecylsilyl silica gel for chromatography R (5-10 \u00b5m).<\/p>\n Mobile phase Dissolve 6.8 g of potassium dihydrogen phosphate R and 3.0 g of hexylamine R in 700 mL of water R, adjust to pH 2.8 with dilute phosphoric acid R, add 60 mL of acetonitrile R and dilute to 1000 mL with water R.<\/p>\n Flow rate\u00a0 1.5 mL\/min.<\/p>\n Detection\u00a0 Spectrophotometer at 250 nm for reference solution (e) and at 316 nm for the other solutions.<\/p>\n Injection\u00a0 10 \u00b5L.<\/p>\n Run time\u00a0 2.5 times the retention time of quinine.<\/p>\n Identification of peaks\u00a0 Use the chromatogram obtained with reference solution (a) to identify the peaks due to quinine and impurity C; use the chromatogram obtained with reference solution (b) to identify the peaks due to impurity A and dihydroquinidine; the chromatogram obtained with reference solution (c) shows 4 peaks due to impurity A, quinine, dihydroquinidine and impurity C which are identified by comparison of their retention times with those of the corresponding peaks in the chromatograms obtained with reference solutions (a) and (b).<\/p>\n Relative retention\u00a0 With reference to quinine: impurity C = about 1.4.<\/p>\n Relative retention\u00a0 With reference to impurity A: dihydroquinidine = about 1.5.<\/p>\n System suitability:<\/p>\n \u2014 resolution: minimum 3.0 between the peaks due to quinine and impurity A and minimum 2.0 between the peaks due to dihydroquinidine and quinine in the chromatogram obtained with reference solution (c);<\/p>\n \u2014 signal-to-noise ratio: minimum 4 for the principal peak in the chromatogram obtained with reference solution (d);<\/p>\n \u2014 mass distribution ratio: 3.5 to 4.5 for the peak due to impurity A in the chromatogram obtained with reference solution (b), tR\u2032 being calculated from the peak due to thiourea in the chromatogram obtained with reference solution (e); if necessary, adjust the concentration of acetonitrile in the mobile phase.<\/p>\n Limits:<\/p>\n \u2014 impurity C: maximum 10 per cent;<\/p>\n \u2014 any impurity eluted before quinine: for each impurity, maximum 5 per cent;<\/p>\n \u2014 any other impurity: for each impurity, maximum 2.5 per cent;<\/p>\n \u2014 disregard limit: the area of the principal peak in the chromatogram obtained with reference solution (d) (0.2 per cent).<\/p>\n Loss on drying (2.2.32)<\/strong><\/p>\n 3.0 per cent to 5.0 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 Maximum 0.1 per cent, determined on 1.0 g.<\/p>\n Dissolve 0.300 g in a mixture of 10 mL of chloroform R and 20 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 24.90 mg of C40<\/sub>H50<\/sub>N4<\/sub>O8<\/sub>S.<\/p>\n Protected from light.<\/p>\n A. (S)-[(2R,4S,5R)-5-ethenyl-1-azabicyclo[2.2.2]oct-2-yl](6-methoxyquinolin-4-yl)methanol (quinidine),<\/p>\n B. (R)-[(2S,4S,5R)-5-ethenyl-1-azabicyclo[2.2.2]oct-2-yl](quinolin-4-yl)methanol (cinchonidine),<\/p>\n C. (R)-[(2S,4S,5R)-5-ethyl-1-azabicyclo[2.2.2]oct-2-yl](6-methoxyquinolin-4-yl)methanol (dihydroquinine).<\/p>\n","protected":false},"excerpt":{"rendered":" Edition: BP 2025 (Ph. Eur. 11.6 update) Action and use Antiprotozoal (malaria). Preparations Quinine Sulfate Oral Suspension Quinine Sulfate Tablets DEFINITION Alkaloid monosulfates, expressed as bis[(R)-[(2S,4S,5R)-5-ethenyl-1-azabicyclo[2.2.2]oct-2-yl](6-methoxyquinolin-4- yl)methanol] sulfate dihydrate. Content 99.0 per cent to 101.0 per cent (dried substance). CHARACTERS Appearance White or almost white, crystalline powder or fine, colourless needles. Solubility Slightly soluble in…<\/p>\n","protected":false},"author":5,"featured_media":28805,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-28804","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\/28804","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=28804"}],"version-history":[{"count":2,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/28804\/revisions"}],"predecessor-version":[{"id":28809,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/28804\/revisions\/28809"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/28805"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=28804"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=28804"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=28804"}],"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
Other cinchona alkaloids<\/h3>\n
ASSAY<\/h2>\n
STORAGE<\/h2>\n
IMPURITIES<\/h2>\n