{"id":9997,"date":"2025-10-07T11:38:03","date_gmt":"2025-10-07T04:38:03","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=9997"},"modified":"2025-10-07T11:38:03","modified_gmt":"2025-10-07T04:38:03","slug":"deferasirox","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/deferasirox\/","title":{"rendered":"Deferasirox"},"content":{"rendered":"

(Ph. Eur. monograph 2933)<\/p>\n

C_{21<\/sub>H_{15<\/sub>N_{3<\/sub>O_{4<\/sub>\u00a0 \u00a0 \u00a0 373.4\u00a0 \u00a0 \u00a0 \u00a0201530-41-8<\/p>\n}}}}

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

Selective iron(III) chelator; treatment of iron overload<\/p>\n

Preparation<\/strong><\/p>\n

Deferasirox Dispersible Tablets<\/p>\n

DEFINITION<\/h2>\n
4-[3,5-Bis(2-hydroxyphenyl)-1H-1,2,4-triazol-1-yl]benzoic acid.<\/p>\n
Content<\/h3>\n
98.0 per cent to 102.0 per cent (anhydrous substance).<\/p>\n
CHARACTERS<\/h2>\n
Appearance<\/h3>\n
White or slightly yellow powder.<\/p>\n
Solubility<\/h3>\n
Practically insoluble in water, very soluble in dimethyl sulfoxide, slightly soluble in anhydrous ethanol, practically insoluble in heptane.<\/p>\n
It shows polymorphism (5.9).<\/p>\n
IDENTIFICATION<\/h2>\n
Infrared absorption spectrophotometry (2.2.24).<\/p>\n
Comparison: deferasirox CRS.<\/p>\n
TESTS<\/h2>\n
Related substances<\/h3>\n
Liquid chromatography (2.2.29). Use only colourless glassware. Store the solutions at 2-8 \u00b0C.<\/p>\n
Buffer solution: 0.100 g\/L solution of sodium edetate R adjusted to pH 2.1 with phosphoric acid R.<\/p>\n
Solvent mixture” 0.040 g\/L solution of sodium edetate R, acetonitrile R (25:75 V\/V).<\/p>\n
Test solution (a): Dissolve 30.0 mg of the substance to be examined in 15 mL of the solvent mixture with vigorous shaking (this may take up to 20 min) and dilute to 20.0 mL with the solvent mixture.
\nTest solution (b) Dissolve 25.0 mg of the substance to be examined in the solvent mixture and dilute to 100.0 mL with the solvent mixture.<\/p>\n
Reference solution (a): Dissolve 25.0 mg of deferasirox CRS in the solvent mixture and dilute to 100.0 mL with the solvent mixture.<\/p>\n
Reference solution (b): Dilute 1.0 mL of test solution (a) to 100.0 mL with the solvent mixture. Dilute 1.0 mL of this solution to 20.0 mL with the solvent mixture.<\/p>\n
Reference solution (c): Dissolve the contents of a vial of deferasirox for system suitability A CRS (containing impurity D) in 1.0 mL of the solvent mixture.<\/p>\n
Reference solution (d): Dissolve 3.0 mg of deferasirox impurity B CRS in the solvent mixture and dilute to 20.0 mL with the solvent mixture. Dilute 5.0 mL of the solution to 100.0 mL with the solvent mixture. Dilute 3.0 mL of this solution to 50.0 mL with the solvent mixture.<\/p>\n
Column:<\/p>\n
\u2014 size: l = 0.15 m, \u00d8 = 3.0 mm;<\/p>\n
\u2014 stationary phase: end-capped octadecylsilyl silica gel for chromatography with embedded polar groups R (3.5 \u03bcm);<\/p>\n
\u2014 temperature: 60 \u00b0C.<\/p>\n
Mobile phase:<\/p>\n
\u2014 mobile phase A: acetonitrile R, buffer solution, water for chromatography R (10:10:80 V\/V\/V);<\/p>\n
\u2014 mobile phase B: buffer solution, acetonitrile R (10:90 V\/V);<\/p>\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 – 10<\/td>\n 62<\/td>\n 38<\/td>\n<\/tr>\n
10 – 14<\/td>\n 62 \u2192 0<\/td>\n 38 \u2192 100<\/td>\n<\/tr>\n
14 – 16<\/td>\n 0<\/td>\n 100<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n
Flow rate: 0.8 mL\/min.<\/p>\n
Detection: Spectrophotometer at 250 nm.<\/p>\n
Autosampler: Set at 5 \u00b0C.<\/p>\n
Injection: 5 \u03bcL of test solution (a) and reference solutions (b), (c) and (d).<\/p>\n
Identification of impurities: Use the chromatogram supplied with deferasirox for system suitability A CRS and the chromatogram obtained with reference solution (c) to identify the peak due to impurity D; use the chromatogram obtained with reference solution (d) to identify the peak due to impurity B.<\/p>\n
Relative retention: With reference to deferasirox (retention time = about 10 min): impurity B = about 0.5;
\nimpurity D = about 0.95.<\/p>\n
System suitability:<\/p>\n
\u2014 resolution: minimum 1.5 between the peaks due to impurity D and deferasirox in the chromatogram obtained with reference solution (c);<\/p>\n
\u2014 signal-to-noise ratio: minimum 10 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 deferasirox in reference solution (b).<\/p>\n
Limits:<\/p>\n
\u2014 unspecified impurities: for each impurity, maximum 0.05 per cent;<\/p>\n
\u2014 total: maximum 0.2 per cent;<\/p>\n
\u2014 reporting threshold: 0.03 per cent.<\/p>\n
Impurity F<\/h3>\n
Liquid chromatography (2.2.29). Protect the solutions from light.<\/p>\n
Solvent mixture: phosphoric acid R, water R, acetone R (25:100:900 V\/V\/V).<\/p>\n
Test solution: Dissolve 0.600 g of the substance to be examined in 1 mL of dimethyl sulfoxide R, add 2 mL of the solvent mixture and mix thoroughly using a vortex mixer. Heat the solution at 45 \u00b0C for 35 min, then cool to 2-8 \u00b0C for 1 h. Dilute to 5.0 mL with mobile phase A, previously cooled to 2-8 \u00b0C. Shake vigorously using a mechanical shaker for 2 min. Centrifuge immediately at 4000 g for 5 min and filter the supernatant through a membrane filter (nominal pore size 0.45 \u03bcm). If a precipitation is still observed, allow to stand for 1 h at 2-8 \u00b0C. Filter again through a membrane filter (nominal pore size 0.45 \u03bcm) immediately before injection.<\/p>\n
Reference solution (a): Dissolve 6.0 mg of deferasirox impurity F CRS in 1 mL of dimethyl sulfoxide R and dilute to 20.0 mL with water R. Dilute 1.0 mL of the solution to 10.0 mL with dimethyl sulfoxide R.<\/p>\n
Reference solution (b): Dilute 1.0 mL of reference solution (a) to 10.0 mL with dimethyl sulfoxide R. To 1.0 mL of this solution add 5 mL of dimethyl sulfoxide R and 20 mL of the solvent mixture. Heat this solution at 45 \u00b0C for 35 min, cool to 2-8 \u00b0C and dilute to 50.0 mL with mobile phase A, previously cooled to 2-8 \u00b0C.<\/p>\n
Reference solution (c): To 2.0 mL of reference solution (b) add 1 mL of dimethyl sulfoxide R and 4 mL of the solvent mixture and dilute to 10.0 mL with mobile phase A.<\/p>\n
Column:<\/p>\n
\u2014 size: l = 0.15 m, \u00d8 = 3.0 mm;<\/p>\n
\u2014 stationary phase: end-capped octadecylsilyl silica gel for chromatography R (3.5 \u03bcm);<\/p>\n
\u2014 temperature: 40 \u00b0C.<\/p>\n
Mobile phase:<\/p>\n
\u2014 mobile phase A: phosphoric acid R, acetonitrile R, water for chromatography R (2:100:900 V\/V\/V);<\/p>\n
\u2014 mobile phase B: phosphoric acid R, water for chromatography R, acetonitrile R (2:100:900 V\/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 – 2<\/td>\n 90<\/td>\n 10<\/td>\n<\/tr>\n
2 – 8<\/td>\n 90 \u2192 58<\/td>\n 10 \u2192 42<\/td>\n<\/tr>\n
8 – 8.1<\/td>\n 58 \u2192 0<\/td>\n 42 \u2192 100<\/td>\n<\/tr>\n
8.1 – 16<\/td>\n 0<\/td>\n 100<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n
Flow rate: 1.0 mL\/min.<\/p>\n
Detection: Spectrophotometer at 316 nm.<\/p>\n
Injection: 25 \u03bcL of the test solution and reference solutions (b) and (c).<\/p>\n
Relative retention: With reference to deferasirox (retention time = about 10 min): impurity F acetone
\nderivative = about 0.5.<\/p>\n
System suitability:<\/p>\n
\u2014 signal-to-noise ratio: minimum 10 for the peak due to impurity F acetone derivative in the chromatogram obtained with reference solution (c);<\/p>\n
\u2014 repeatability: maximum relative standard deviation of 5.0 per cent for the area of the peak due to impurity F acetone derivative determined on 6 injections of reference solution (b).<\/p>\n
Calculation of percentage content:<\/p>\n
\u2014 for impurity F, use the concentration of impurity F in reference solution (b).<\/p>\n
Limit:<\/p>\n
\u2014 impurity F: maximum 0.5 ppm.<\/p>\n
Water (2.5.12)<\/h4>\n
Maximum 0.5 per cent, determined on 1.00 g.<\/p>\n
Sulfated ash (2.4.14)<\/h4>\n
Maximum 0.1 per cent, determined on 1.0 g.<\/p>\n
ASSAY<\/h2>\n
Liquid chromatography (2.2.29) as described in the test for related substances with the following modification.<\/p>\n
Injection Test solution (b) and reference solution (a).<\/p>\n
Calculate the percentage content of C_{21<\/sub>H_{15<\/sub>N_{3<\/sub>O_{4<\/sub>\u00a0taking into account the assigned content of deferasirox CRS.<\/p>\n}}}}
IMPURITIES<\/h2>\n
Specified impurities F.<\/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, B, C, D, E.<\/p>\n
$\"Deferasirox\"$ <\/p>\n
A. 2-hydroxy-N-(2-hydroxybenzoyl)benzamide,<\/p>\n
$\"Deferasirox\"$ <\/p>\n
B. 2-(2-hydroxyphenyl)-4H-1,3-benzoxazin-4-one,<\/p>\n
$\"Deferasirox\"$ <\/p>\n
C. 2-[3,5-bis(2-hydroxyphenyl)-1H-1,2,4-triazol-1-yl]benzoic acid,<\/p>\n
$\"Deferasirox\"$ <\/p>\n
D. 3-[3,5-bis(2-hydroxyphenyl)-1H-1,2,4-triazol-1-yl]benzoic acid,<\/p>\n
$\"Deferasirox\"$ <\/p>\n
E. ethyl 4-[3,5-bis(2-hydroxyphenyl)-1H-1,2,4-triazol-1-yl]benzoate,<\/p>\n
$\"Deferasirox\"$ <\/p>\n
F. 4-hydrazinylbenzoic acid.<\/p>\n","protected":false},"excerpt":{"rendered":"
(Ph. Eur. monograph 2933) C21H15N3O4\u00a0 \u00a0 \u00a0 373.4\u00a0 \u00a0 \u00a0 \u00a0201530-41-8 Action and use Selective iron(III) chelator; treatment of iron overload Preparation Deferasirox Dispersible Tablets DEFINITION 4-[3,5-Bis(2-hydroxyphenyl)-1H-1,2,4-triazol-1-yl]benzoic acid. Content 98.0 per cent to 102.0 per cent (anhydrous substance). CHARACTERS Appearance White or slightly yellow powder. Solubility Practically insoluble in water, very soluble in dimethyl sulfoxide,…<\/p>\n","protected":false},"author":2,"featured_media":10036,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[174],"tags":[],"class_list":["post-9997","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\/9997","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\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/comments?post=9997"}],"version-history":[{"count":2,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/9997\/revisions"}],"predecessor-version":[{"id":10038,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/9997\/revisions\/10038"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/10036"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=9997"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=9997"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=9997"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}

Content<\/h3>\n98.0 per cent to 102.0 per cent (anhydrous substance).<\/p>\n

CHARACTERS<\/h2>\n

Appearance<\/h3>\nWhite or slightly yellow powder.<\/p>\n

Solubility<\/h3>\nPractically insoluble in water, very soluble in dimethyl sulfoxide, slightly soluble in anhydrous ethanol, practically insoluble in heptane.<\/p>\nIt shows polymorphism (5.9).<\/p>\n

IDENTIFICATION<\/h2>\nInfrared absorption spectrophotometry (2.2.24).<\/p>\nComparison: deferasirox CRS.<\/p>\n

TESTS<\/h2>\n

Water (2.5.12)<\/h4>\nMaximum 0.5 per cent, determined on 1.00 g.<\/p>\n

Sulfated ash (2.4.14)<\/h4>\nMaximum 0.1 per cent, determined on 1.0 g.<\/p>\n

Content<\/h3>\n
98.0 per cent to 102.0 per cent (anhydrous substance).<\/p>\n

Appearance<\/h3>\n
White or slightly yellow powder.<\/p>\n

Solubility<\/h3>\n
Practically insoluble in water, very soluble in dimethyl sulfoxide, slightly soluble in anhydrous ethanol, practically insoluble in heptane.<\/p>\n
It shows polymorphism (5.9).<\/p>\n

IDENTIFICATION<\/h2>\n
Infrared absorption spectrophotometry (2.2.24).<\/p>\n
Comparison: deferasirox CRS.<\/p>\n

Water (2.5.12)<\/h4>\n
Maximum 0.5 per cent, determined on 1.00 g.<\/p>\n

Sulfated ash (2.4.14)<\/h4>\n
Maximum 0.1 per cent, determined on 1.0 g.<\/p>\n