{"id":10066,"date":"2025-10-07T14:13:40","date_gmt":"2025-10-07T07:13:40","guid":{"rendered":"https:\/\/nhathuocngocanh.com\/bp\/?p=10066"},"modified":"2025-11-15T15:05:05","modified_gmt":"2025-11-15T08:05:05","slug":"desferrioxamine-mesilate","status":"publish","type":"post","link":"https:\/\/nhathuocngocanh.com\/bp\/desferrioxamine-mesilate\/","title":{"rendered":"Desferrioxamine Mesilate"},"content":{"rendered":"

(Deferoxamine Mesilate, Ph. Eur. monograph 0896)<\/p>\n

C_{26<\/sub>H_{52<\/sub>N_{6<\/sub>O_{11<\/sub>S\u00a0 \u00a0 \u00a0 \u00a0 657\u00a0 \u00a0 \u00a0 \u00a038-14-7<\/p>\n}}}}

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

Chelating agent (iron).<\/p>\n

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

Desferrioxamine Injection<\/p>\n

DEFINITION<\/h2>\n
N -[5-(4-[(5-Aminopentyl)(hydroxy)amino]-4-oxobutanamido)pentyl]-N -hydroxy-N -[5-(N-
\nhydroxyacetamido)pentyl]butanediamide methanesulfonate.<\/p>\n
Content<\/h3>\n
98.0 per cent to 102.0 per cent (anhydrous substance).<\/p>\n
PRODUCTION<\/h2>\n
It is considered that alkyl methanesulfonate esters are genotoxic and are potential impurities in deferoxamine mesilate.<\/p>\n
The manufacturing process should be developed taking into consideration the principles of quality risk management, together with considerations of the quality of starting materials, process capability and validation. The general methods 2.5.37. Methyl, ethyl and isopropyl methanesulfonate in methanesulfonic acid, 2.5.38. Methyl, ethyl and isopropyl methanesulfonate in active substances and 2.5.39. Methanesulfonyl chloride in methanesulfonic acid are available to assist manufacturers.<\/p>\n
CHARACTERS<\/h2>\n
Appearance<\/h3>\n
White or almost white powder.<\/p>\n
Solubility<\/h3>\n
Freely soluble in water, slightly soluble in methanol, very slightly soluble in ethanol (96 per cent).<\/p>\n
IDENTIFICATION<\/h2>\n
A. Infrared absorption spectrophotometry (2.2.24).<\/p>\n
Comparison: deferoxamine mesilate CRS.<\/p>\n
B. Dissolve 0.1 g in 5 mL of dilute hydrochloric acid R. Add 1 mL of barium chloride solution R2. The solution is clear. In a porcelain crucible, mix 0.1 g with 1 g of anhydrous sodium carbonate R, heat and ignite over a naked flame. Allow to cool.<\/p>\n
Dissolve the residue in 10 mL of water R, heating if necessary, and filter. The filtrate gives reaction (a) of sulfates (2.3.1).<\/p>\n
TESTS<\/h2>\n
Solution S<\/h3>\n
Dissolve 2.5 g in carbon dioxide-free water R prepared from distilled water R and dilute to 25 mL with the same solvent.<\/p>\n
Appearance of solution<\/h3>\n
Solution S is clear (2.2.1) and not more intensely coloured than reference solution Y_{5<\/sub> (2.2.2, Method II).<\/p>\n}
pH (2.2.3)<\/h4>\n
4.0 to 6.0.<\/p>\n
Dilute 1 mL of freshly prepared solution S to 10 mL with carbon dioxide-free water R prepared from distilled water R.<\/p>\n
Related substances<\/h3>\n
Liquid chromatography (2.2.29). Prepare the solutions immediately before use and protect from light.<\/p>\n
A. Deferoxamine mesilate produced by fermentation.<\/p>\n
Solvent mixture: acetonitrile R, water R (6:94 V\/V).<\/p>\n
Test solution: Dissolve 25 mg of the substance to be examined in 10 mL of the solvent mixture and dilute to 25.0 mL with the solvent mixture.<\/p>\n
Reference solution (a): Dilute 1.0 mL of the test solution to 100.0 mL with the solvent mixture.<\/p>\n
Reference solution (b): Dissolve 5 mg of deferoxamine for system suitability CRS (containing impurity A) in mobile phase A and dilute to 5 mL with the solvent mixture.<\/p>\n
Column:<\/p>\n
\u2014 size: l = 0.075 m, \u00d8 = 4.6 mm;<\/p>\n
\u2014 stationary phase: octadecylsilyl silica gel for chromatography R (3.5 \u03bcm);<\/p>\n
\u2014 temperature: 32 \u00b0C.<\/p>\n
Mobile phase:<\/p>\n
\u2014 mobile phase A: 1.32 g\/L solution of ammonium phosphate R adjusted to pH 3.0 with phosphoric acid R;<\/p>\n
\u2014 mobile phase B: mixture of equal volumes of acetonitrile for chromatography R and mobile phase A;<\/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 – 4<\/td>\n 88<\/td>\n 12<\/td>\n<\/tr>\n
4 – 20<\/td>\n 88 \u2192 80<\/td>\n 12 \u2192 20<\/td>\n<\/tr>\n
20 – 35<\/td>\n 80 \u2192 57.5<\/td>\n 20 \u2192 42.5<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n
Flow rate: 1.5 mL\/min.<\/p>\n
Detection: Spectrophotometer at 220 nm.<\/p>\n
Injection: 20 \u03bcL.<\/p>\n
Identification of impurities: Use the chromatogram obtained with reference solution (b) to identify the peak due to impurity A.<\/p>\n
Relative retention: With reference to deferoxamine (retention time = about 18 min): impurity A = about 0.9.
\nSystem suitability Reference solution (b):<\/p>\n
\u2014 resolution: minimum 2.0 between the peaks due to impurity A and deferoxamine.<\/p>\n
Calculation of percentage contents:<\/p>\n
\u2014 for each impurity, use the concentration of deferoxamine mesilate in reference solution (a).<\/p>\n
Limits:<\/p>\n
\u2014 impurity A: maximum 2.0 per cent;<\/p>\n
\u2014 any other impurity: for each impurity, maximum 0.8 per cent;<\/p>\n
\u2014 total: maximum 5.0 per cent;<\/p>\n
\u2014 reporting threshold: 0.05 per cent.<\/p>\n
The thresholds indicated under Related substances (Table 2034.-1) in the general monograph Substances for pharmaceutical use (2034) do not apply.<\/p>\n
B. Deferoxamine mesilate produced by a synthetic process.<\/p>\n
Solvent mixture: Mobile phase B, mobile phase A (20:80 V\/V).<\/p>\n
Test solution: Dissolve 0.125 g of the substance to be examined in the solvent mixture and dilute to 10.0 mL with the solvent mixture.<\/p>\n
Reference solution (a): Dilute 1.0 mL of the test solution to 100.0 mL with the solvent mixture. Dilute 1.0 mL of this solution to 10.0 mL with the solvent mixture.<\/p>\n
Reference solution (b): Dissolve 12.5 mg of deferoxamine for peak identification CRS (containing impurities F, G, H, I and J) in the solvent mixture and dilute to 1 mL with the solvent mixture.<\/p>\n
Column:<\/p>\n
\u2014 size: l = 0.15 m, \u00d8 = 4.6 mm;<\/p>\n
\u2014 stationary phase: end-capped octadecylsilyl silica gel for chromatography R (5 \u03bcm);<\/p>\n
\u2014 temperature: 25 \u00b0C.<\/p>\n
Mobile phase:<\/p>\n
\u2014 mobile phase A: dissolve 0.605 g of sodium edetate R in 900 mL of water for chromatography R, add 1.0 mL of phosphoric acid R and adjust to pH 6.0 with concentrated ammonia R; dilute to 1000 mL with water for chromatography R;<\/p>\n
\u2014 mobile phase B: dissolve 0.780 g of sodium edetate R in 750 mL of water for chromatography R and add 1.0 mL of phosphoric acid R; add 250 mL of acetonitrile for chromatography R, mix thoroughly and adjust the apparent pH to 6.0 with concentrated ammonia R;<\/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<\/td>\n 80<\/td>\n 20<\/td>\n<\/tr>\n
0 – 21.6<\/td>\n 80 \u2192 20<\/td>\n 20 \u2192 80<\/td>\n<\/tr>\n
21.6 – 31.6<\/td>\n 20<\/td>\n 80<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n
Flow rate: 1.5 mL\/min.<\/p>\n
Detection: Spectrophotometer at 220 nm.<\/p>\n
Injection: 20 \u03bcL.<\/p>\n
Identification of impurities: Use the chromatogram supplied with deferoxamine for peak identification CRS and the chromatogram obtained with reference solution (b) to identify the peaks due to impurities F, G, H, I and J.<\/p>\n
Relative retention: With reference to deferoxamine (retention time = about 12.9 min): impurity I = about 0.5;
\nimpurity F = about 0.96; impurity G = about 0.98; impurity H = about 1.2; impurities J and K = about 1.37.<\/p>\n
System suitability: Reference solution (b):<\/p>\n
\u2014 peak-to-valley ratio: minimum 3.0, where Hp = height above the baseline of the peak due to impurity G and H_{v<\/sub> = height above the baseline of the lowest point of the curve separating this peak from the peak due to deferoxamine.<\/p>\n}
Calculation of percentage contents:<\/p>\n
\u2014 correction factor: multiply the peak area of impurity I by 1.4;<\/p>\n
\u2014 for each impurity, use the concentration of deferoxamine mesilate in reference solution (a).<\/p>\n
Limits:<\/p>\n
\u2014 impurities F, H: for each impurity, maximum 0.5 per cent;<\/p>\n
\u2014 impurities G, I: for each impurity, maximum 0.3 per cent;<\/p>\n
\u2014 sum of impurities J and K: maximum 0.5 per cent;<\/p>\n
\u2014 unspecified impurities: for each impurity, maximum 0.20 per cent;<\/p>\n
\u2014 total: maximum 2.0 per cent;<\/p>\n
\u2014 reporting threshold: 0.03 per cent.<\/p>\n
The thresholds indicated under Related substances (Table 2034.-1) in the general monograph Substances for pharmaceutical use (2034) do not apply.<\/p>\n
Chlorides (2.4.4)<\/h3>\n
Maximum 330 ppm.<\/p>\n
Dilute 2 mL of solution S to 20 mL with water R.<\/p>\n
Sulfates (2.4.13)<\/h3>\n
Maximum 400 ppm.<\/p>\n
Dilute 5 mL of solution S to 20 mL with distilled water R.<\/p>\n
Water (2.5.12)<\/h4>\n
Maximum 2.0 per cent, determined on 1.000 g.<\/p>\n
Sulfated ash (2.4.14)<\/h4>\n
Maximum 0.1 per cent, determined on 1.0 g.<\/p>\n
Bacterial endotoxins (2.6.14)<\/h4>\n
Less than 0.025 IU\/mg, if intended for use in the manufacture of parenteral preparations without a further appropriate procedure for the removal of bacterial endotoxins. Since deferoxamine mesilate has an inhibitory effect on the bacterial endotoxins test, a suitable procedure is put in place to remove this inhibitory effect. The monocyte-activation test (2.6.30) has been found suitable to overcome this issue.<\/p>\n
ASSAY<\/h2>\n
Dissolve 0.500 g in 50 mL of water R. Add 4 mL of dilute sulfuric acid R1. Titrate with 0.1 M ferric ammonium sulfate. To accelerate the titration, add 4.5 mL quickly, stop for 1.5 min and continue to titrate uniformly at a rate of about 0.2 mL\/min.<\/p>\n
Determine the end-point potentiometrically (2.2.20) using a platinum indicator electrode and a suitable reference electrode.<\/p>\n
1 mL of 0.1 M ferric ammonium sulfate is equivalent to 65.68 mg of C_{26<\/sub>H_{52<\/sub>N_{6<\/sub>O_{11<\/sub>S.<\/p>\n}}}}
STORAGE<\/h2>\n
Protected from light. If the substance is sterile, store in a sterile, airtight, tamper-evident container.<\/p>\n
LABELLING<\/h2>\n
The label states the origin of the substance:<\/p>\n
\u2014 produced by fermentation;<\/p>\n
\u2014 produced by a synthetic process.<\/p>\n
IMPURITIES<\/h2>\n
Test A for related substances: A, B, C, J.<\/h3>\n
Test B for related substances: E, F, G, H, I, J, K.<\/h3>\n
Specified impurities: A, F, G, H, I, J, K.<\/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. 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) B, C, E.<\/p>\n
$\"Desferrioxamine$ <\/p>\n
A. N -[5-(4-[(4-aminobutyl)(hydroxy)amino]-4-oxobutanamido)pentyl]-N -hydroxy-N -[5-(N-
\nhydroxyacetamido)pentyl]butanediamide,<\/p>\n
$\"Desferrioxamine$ <\/p>\n
B. N -(5-aminopentyl)-N -hydroxy-N -[5-(N-hydroxyacetamido)pentyl]butanediamide,<\/p>\n
$\"Desferrioxamine$ <\/p>\n
C. N-[5-(2,5-dioxopyrrolidin-1-yl)pentyl]-N-hydroxyacetamide,<\/p>\n
$\"Desferrioxamine$ <\/p>\n
E. methyl 4-[[5-[[4-[(5-aminopentyl)(hydroxy)amino]-4-oxobutanamido]pentyl](hydroxy)amino]-4-oxobutanoate,<\/p>\n
$\"Desferrioxamine$ <\/p>\n
F. N -(5-acetamidopentyl)-N -[5-[4-[(5-aminopentyl)(hydroxyl)amino]-4-oxobutanamido]pentyl]-N -hydroxybutanediamide,<\/p>\n
G. unknown structure,<\/p>\n
$\"Desferrioxamine$ <\/p>\n
H. N ,N -bis(5-aminopentyl)-N ,N ,11,27-tetrahydroxy-4,12,15,23,26,34-hexaoxo-5,11,16,22,27,33-
\nhexaazaheptatriacontane-1,37-diamide,<\/p>\n
$\"Desferrioxamine$ <\/p>\n
I. N -(5-aminopentyl)-N -[5-(4-[(5-aminopentyl)(hydroxy)amino]-4-oxobutanamido)pentyl]- N -hydroxybutanediamide,<\/p>\n
$\"Desferrioxamine$ <\/p>\n
J. N -(5-aminopentyl)-N ,11,22-trihydroxy-N -[5-(N-hydroxyacetamido)pentyl]-4,12,15,23-tetraoxo-5,11,16,22- tetraazahexacosane-1,26-diamide,<\/p>\n
$\"Desferrioxamine$ <\/p>\n
K. 22-(acetyloxy)-N ,N -bis(5-aminopentyl)-N ,N ,11,33-tetrahydroxy-4,12,15,29,32,40-hexaoxo-5,11,16,22,28,33,39- heptaazatritetracontane-1,43-diamide.<\/p>\n","protected":false},"excerpt":{"rendered":"
(Deferoxamine Mesilate, Ph. Eur. monograph 0896) C26H52N6O11S\u00a0 \u00a0 \u00a0 \u00a0 657\u00a0 \u00a0 \u00a0 \u00a038-14-7 Action and use Chelating agent (iron). Preparation Desferrioxamine Injection DEFINITION N -[5-(4-[(5-Aminopentyl)(hydroxy)amino]-4-oxobutanamido)pentyl]-N -hydroxy-N -[5-(N- hydroxyacetamido)pentyl]butanediamide methanesulfonate. Content 98.0 per cent to 102.0 per cent (anhydrous substance). PRODUCTION It is considered that alkyl methanesulfonate esters are genotoxic and are potential impurities in…<\/p>\n","protected":false},"author":2,"featured_media":10160,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[1],"tags":[],"class_list":["post-10066","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-volumes-1-2"],"acf":[],"_links":{"self":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/10066","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=10066"}],"version-history":[{"count":1,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/10066\/revisions"}],"predecessor-version":[{"id":10162,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/posts\/10066\/revisions\/10162"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media\/10160"}],"wp:attachment":[{"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/media?parent=10066"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/categories?post=10066"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/nhathuocngocanh.com\/bp\/wp-json\/wp\/v2\/tags?post=10066"}],"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 almost white powder.<\/p>\n

Solubility<\/h3>\nFreely soluble in water, slightly soluble in methanol, very slightly soluble in ethanol (96 per cent).<\/p>\n

TESTS<\/h2>\n

Solution S<\/h3>\nDissolve 2.5 g in carbon dioxide-free water R prepared from distilled water R and dilute to 25 mL with the same solvent.<\/p>\n

Appearance of solution<\/h3>\nSolution S is clear (2.2.1) and not more intensely coloured than reference solution Y5<\/sub> (2.2.2, Method II).<\/p>\n

pH (2.2.3)<\/h4>\n4.0 to 6.0.<\/p>\nDilute 1 mL of freshly prepared solution S to 10 mL with carbon dioxide-free water R prepared from distilled water R.<\/p>\n

Chlorides (2.4.4)<\/h3>\nMaximum 330 ppm.<\/p>\nDilute 2 mL of solution S to 20 mL with water R.<\/p>\n

Sulfates (2.4.13)<\/h3>\nMaximum 400 ppm.<\/p>\nDilute 5 mL of solution S to 20 mL with distilled water R.<\/p>\n

Water (2.5.12)<\/h4>\nMaximum 2.0 per cent, determined on 1.000 g.<\/p>\n

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

STORAGE<\/h2>\nProtected from light. If the substance is sterile, store in a sterile, airtight, tamper-evident container.<\/p>\n

LABELLING<\/h2>\nThe label states the origin of the substance:<\/p>\n\u2014 produced by fermentation;<\/p>\n\u2014 produced by a synthetic process.<\/p>\n

IMPURITIES<\/h2>\n

Test A for related substances: A, B, C, J.<\/h3>\n

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

Appearance<\/h3>\n
White or almost white powder.<\/p>\n

Solubility<\/h3>\n
Freely soluble in water, slightly soluble in methanol, very slightly soluble in ethanol (96 per cent).<\/p>\n

Solution S<\/h3>\n
Dissolve 2.5 g in carbon dioxide-free water R prepared from distilled water R and dilute to 25 mL with the same solvent.<\/p>\n

Appearance of solution<\/h3>\n
Solution S is clear (2.2.1) and not more intensely coloured than reference solution Y_{5<\/sub> (2.2.2, Method II).<\/p>\n}

pH (2.2.3)<\/h4>\n
4.0 to 6.0.<\/p>\n
Dilute 1 mL of freshly prepared solution S to 10 mL with carbon dioxide-free water R prepared from distilled water R.<\/p>\n

Chlorides (2.4.4)<\/h3>\n
Maximum 330 ppm.<\/p>\n
Dilute 2 mL of solution S to 20 mL with water R.<\/p>\n

Sulfates (2.4.13)<\/h3>\n
Maximum 400 ppm.<\/p>\n
Dilute 5 mL of solution S to 20 mL with distilled water R.<\/p>\n

Water (2.5.12)<\/h4>\n
Maximum 2.0 per cent, determined on 1.000 g.<\/p>\n

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

STORAGE<\/h2>\n
Protected from light. If the substance is sterile, store in a sterile, airtight, tamper-evident container.<\/p>\n

LABELLING<\/h2>\n
The label states the origin of the substance:<\/p>\n
\u2014 produced by fermentation;<\/p>\n
\u2014 produced by a synthetic process.<\/p>\n