{"id":30860,"date":"2025-11-12T16:17:50","date_gmt":"2025-11-12T09:17:50","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=30860"},"modified":"2025-11-12T16:17:50","modified_gmt":"2025-11-12T09:17:50","slug":"sulfasalazine","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/sulfasalazine\/","title":{"rendered":"Sulfasalazine"},"content":{"rendered":"

(Ph. Eur. monograph 0863)<\/em><\/p>\n

C18<\/sub>H14<\/sub>N4<\/sub>O5<\/sub>S 398.4 599-79-1<\/p>\n

Action and use<\/strong><\/p>\n

Sulfonamide aminosalicylate; treatment of ulcerative colitis.<\/p>\n

Preparations<\/strong><\/p>\n

Sulfasalazine Gastro-resistant Tablets<\/p>\n

Sulfasalazine Tablets<\/p>\n

DEFINITION<\/h2>\n

2-Hydroxy-5-[2-[4-(pyridin-2-ylsulfamoyl)phenyl]diazenyl]benzoic acid.<\/p>\n

Content<\/h3>\n

97.0 per cent to 101.5 per cent (dried substance).<\/p>\n

CHARACTERS<\/h2>\n

Appearance<\/h3>\n

Bright yellow or brownish-yellow, fine powder.<\/p>\n

Solubility<\/h3>\n

Practically insoluble in water, very slightly soluble in ethanol (96 per cent), practically insoluble in methylene chloride. It dissolves in dilute solutions of alkali hydroxides.<\/p>\n

IDENTIFICATION<\/h2>\n

Infrared absorption spectrophotometry (2.2.24).<\/p>\n

Preparation: Discs.<\/p>\n

Comparison: sulfasalazine CRS.<\/p>\n

TESTS<\/h2>\n

Related substances<\/h3>\n

Liquid chromatography (2.2.29).<\/p>\n

Test solution: Dissolve 25.0 mg of the substance to be examined in dilute ammonia R3 and dilute to 25.0 mL with the same solvent.<\/p>\n

Reference solution (a): Dilute 1.0 mL of the test solution to 100.0 mL with dilute ammonia R3.<\/p>\n

Reference solution (b): Dissolve 1.0 mg of sulfasalazine derivative for resolution CRS in 10.0 mL of reference solution (a).<\/p>\n

Dilute 1.0 mL of this solution to 10.0 mL with reference solution (a).<\/p>\n

Column:<\/p>\n

\u2014 size: l = 0.25 m, \u00d8 = 4.6 mm;<\/p>\n

\u2014 stationary phase: octadecylsilyl silica gel for chromatography R (5 \u03bcm).<\/p>\n

Mobile phase:<\/p>\n

\u2014 mobile phase A: in a 1000 mL volumetric flask dissolve 1.13 g of sodium dihydrogen phosphate R and 2.5 g of sodium acetate R in 900 mL of water R; adjust to pH 4.8 with glacial acetic acid R and dilute to 1000 mL with water R;<\/p>\n

\u2014 mobile phase B: mobile phase A, methanol R (10:40 V\/V);<\/p>\n\n\n\n\n\n\n\n
Time<\/strong>
\n(min)<\/strong><\/td>\n		Mobile phase A<\/strong>
\n(per cent V\/V)<\/strong><\/td>\n		Mobile phase B<\/strong>
\n(per cent V\/V)<\/strong><\/td>\n<\/tr>\n
0 – 15<\/td>\n60 \u2192 45<\/td>\n40 \u2192 55<\/td>\n<\/tr>\n
15 – 25<\/td>\n45<\/td>\n55<\/td>\n<\/tr>\n
25 – 60<\/td>\n45 \u2192 0<\/td>\n55 \u2192 100<\/td>\n<\/tr>\n
60 – 65<\/td>\n0<\/td>\n100<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

Flow rate: 1 mL\/min.<\/p>\n

Detection: Spectrophotometer at 320 nm.<\/p>\n

Injection: 20 \u03bcL.<\/p>\n

Relative retention: With reference to sulfasalazine: impurity H = about 0.16; impurity I = about 0.28; impurity C = about 0.80; impurity F = about 0.85; impurity G = about 1.39; impurity E = about 1.63; impurity B = about 1.85; impurity D = about 1.90; impurity A = about 2.00.<\/p>\n

System suitability: Reference solution (b):<\/p>\n

\u2014 resolution: minimum 3.0 between the peaks due to sulfasalazine and sulfasalazine derivative for resolution.<\/p>\n

Limits:<\/p>\n

\u2014 impurities A, B, C, D, E, F, G, I: for each impurity, not more than the area of the principal peak in the chromatogram obtained with reference solution (a) (1 per cent);<\/p>\n

\u2014 total: not more than 4 times the area of the principal peak in the chromatogram obtained with reference solution (a) (4 per cent);<\/p>\n

\u2014 disregard limit: 0.05 times the area of the principal peak in the chromatogram obtained with reference solution (a) (0.05 per cent); disregard any peak with a retention time less than 6 min (due to impurities H and J).<\/p>\n

Impurities H and J<\/h3>\n

Liquid chrom:\u00a0Dissolve 25.0 mg of the substance to be examined in dilute ammonia R3 and dilute to 25.0 mL with the same solvent.<\/span><\/p>\n

Reference solution (a): Dissolve 5.0 mg of salicylic acid R (impurity H) and 5.0 mg of sulfapyridine CRS (impurity J) in dilute ammonia R3 and dilute to 10.0 mL with the same solvent.<\/p>\n

Reference solution (b): Dilute 2.0 mL of reference solution (a) to 100.0 mL with dilute ammonia R3.<\/p>\n

Column:<\/p>\n

\u2014 size: l = 0.25, \u00d8 = 4.6 mm;<\/p>\n

\u2014 stationary phase: octadecylsilyl silica gel for chromatography R (5 \u03bcm).<\/p>\n

Mobile phase: Mobile phase B (described in the test for related substances), mobile phase A (described in the test for related substances) (30:70 V\/V).<\/p>\n

Flow rate: 1 mL\/min.<\/p>\n

Detection: Spectrophotometer at 300 nm.<\/p>\n

Injection: 20 \u03bcL of the test solution and reference solution (b).<\/p>\n

Run time: 10 min.<\/p>\n

Retention time: Impurity H = about 6 min; impurity J = about 7 min.<\/p>\n

System suitability: Reference solution (b):<\/p>\n

\u2014 resolution: minimum 2 between the peaks due to impurities H and J.<\/p>\n

Limits:<\/p>\n

\u2014 impurities H, J: for each impurity, not more than 0.5 times the area of the corresponding peak in the chromatogram obtained with reference solution (b) (0.5 per cent);<\/p>\n

\u2014 disregard limit: 0.05 times the area of the principal peak in the chromatogram obtained with reference solution (b) (0.05 per cent).<\/p>\n

Chlorides (2.4.4)<\/h3>\n

Maximum 140 ppm.<\/p>\n

To 1.25 g add 50 mL of distilled water R. Heat at about 70 \u00b0C for 5 min. Cool and filter. To 20 mL of the filtrate add 1 mL of nitric acid R, allow to stand for 5 min and filter to obtain a clear solution.<\/p>\n

Sulfates (2.4.13)<\/h3>\n

Maximum 400 ppm.<\/p>\n

To 20 mL of the filtrate prepared for the test for chlorides add 1 mL of dilute hydrochloric acid R, allow to stand for 5 min and filter.<\/p>\n

Loss on drying (2.2.32)<\/h3>\n

Maximum 1.0 per cent, determined on 1.000 g by drying in an oven at 105 \u00b0C for 2 h.<\/p>\n

Sulfated ash (2.4.14)<\/h3>\n

Maximum 0.5 per cent, determined on 1.0 g.<\/p>\n

ASSAY<\/h2>\n

Dissolve 0.150 g in 0.1 M sodium hydroxide and dilute to 100.0 mL with the same solvent. Transfer 5.0 mL of this solution to a 1000 mL volumetric flask containing about 750 mL of water R. Add 20.0 mL of a 6 g\/L solution of glacial acetic acid R and dilute to 1000.0 mL with water R. Prepare a standard solution at the same time and in the same manner using 0.150 g of sulfasalazine CRS. Measure the absorbance (2.2.25) of the 2 solutions at the absorption maximum at 359 nm.<\/p>\n

Calculate the content of C18<\/sub>H14<\/sub>N4<\/sub>O5<\/sub>S from the absorbances measured and the concentration of the solutions.<\/p>\n

STORAGE<\/h2>\n

Protected from light.<\/p>\n

IMPURITIES<\/h2>\n

Specified impurities A, B, C, D, E, F, G, H, I, J.<\/p>\n

\"Sulfasalazine\"<\/p>\n

A. 4,4\u2032-[(4-hydroxy-1,3-phenylene)bis(diazenediyl)]bis[N-(pyridin-2-yl)benzenesulfonamide],<\/p>\n

\"Sulfasalazine\"<\/p>\n

B. 2-hydroxy-3,5-bis[2-[4-(pyridin-2-ylsulfamoyl)phenyl]diazenyl]benzoic acid,<\/p>\n

\"Sulfasalazine\"<\/p>\n

C. 2-hydroxy-5-[2-[4-(2-iminopyridin-1(2H)-yl)phenyl]diazenyl]benzoic acid,<\/p>\n

\"Sulfasalazine\"<\/p>\n

D. 4-[2-(2-hydroxyphenyl)diazenyl]-N-(pyridin-2-yl)benzenesulfonamide,<\/p>\n

\"Sulfasalazine\"<\/p>\n

E. 2-hydroxy-4\u2032-(pyridin-2-ylsulfamoyl)-5-[2-[4-(pyridin-2-ylsulfamoyl)phenyl]diazenyl]biphenyl-3-carboxylic acid,<\/p>\n

\"Sulfasalazine\"<\/p>\n

F. 2-hydroxy-3-[2-[4-(pyridin-2-ylsulfamoyl)phenyl]diazenyl]benzoic acid,<\/p>\n

\"Sulfasalazine\"<\/p>\n

G. 5-[2-[4\u2032,5-bis(pyridin-2-ylsulfamoyl)biphenyl-2-yl]diazenyl]-2-hydroxybenzoic acid,<\/p>\n

\"Sulfasalazine\"<\/p>\n

H. 2-hydroxybenzenecarboxylic acid (salicylic acid),<\/p>\n

\"Sulfasalazine\"<\/p>\n

I. 2-hydroxy-5-[2-(4-sulfophenyl)diazenyl]benzoic acid,<\/p>\n

\"Sulfasalazine\"<\/p>\n

J. 4-amino-N-(pyridin-2-yl)benzenesulfonamide (sulfapyridine).<\/p>\n","protected":false},"excerpt":{"rendered":"

(Ph. Eur. monograph 0863) C18H14N4O5S 398.4 599-79-1 Action and use Sulfonamide aminosalicylate; treatment of ulcerative colitis. Preparations Sulfasalazine Gastro-resistant Tablets Sulfasalazine Tablets DEFINITION 2-Hydroxy-5-[2-[4-(pyridin-2-ylsulfamoyl)phenyl]diazenyl]benzoic acid. Content 97.0 per cent to 101.5 per cent (dried substance). CHARACTERS Appearance Bright yellow or brownish-yellow, fine powder. Solubility Practically insoluble in water, very slightly soluble in ethanol (96 per…<\/p>\n","protected":false},"author":4,"featured_media":30913,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-30860","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\/30860","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\/4"}],"replies":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/comments?post=30860"}],"version-history":[{"count":2,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/30860\/revisions"}],"predecessor-version":[{"id":30929,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/30860\/revisions\/30929"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/30913"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=30860"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=30860"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=30860"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}