Deferoxamine Mesylate
(de fer ox' a meen mes' i late).
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C25H48N6O8·CH4O3S 656.79
Butanediamide, N¢-[5-[[4-[[5-(acetylhydroxyamino)pentyl]amino]-1,4-dioxobutyl]hydroxyamino]pentyl]-N-(5-aminopentyl)-N-hydroxy-, monomethanesulfonate;    
N-[5-[3-[(5-Aminopentyl)hydroxycarbamoyl]propionamido]pentyl]-3-[[5-(N-hydroxyacetamido)pentyl]carbamoyl]propionohydroxamic acid monomethanesulfonate (salt)     [138-14-7].
DEFINITION
Change to read:
Deferoxamine Mesylate contains NLT 93.0%(RB 1-May-2011) and NMT 102.0% of C25H48N6O8·CH4O3S, calculated on the anhydrous basis.
IDENTIFICATION
•  B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
ASSAY
Change to read:
•  Procedure
Solution A:  1.32 g/L of dibasic ammonium phosphate in water. Adjust with phosphoric acid to a pH of 3.0.
Solution B:  Acetonitrile and Solution A (1:1)
Mobile phase:  See Table 1.
Table 1
Time
(min)
Solution A
(%)
Solution B
(%)
0 88 12
20 80 20
35 57.5 42.5
35.1 88 12
40 88 12
Diluent:  Acetonitrile and water (6:94)
Standard solution:  1.0 mg/mL of USP Deferoxamine Mesylate RS in Diluent
Sample solution:  1.0 mg/mL of Deferoxamine Mesylate in Diluent
Chromatographic system 
Mode:  LC
Detector:  UV 220 nm
Column:  4.6-mm × 7.5-cm; 3.5-µm packing L1
Column temperature:  32
Autosampler temperature:  5
Flow rate:  1.5 mL/min
Injection size:  20 µL
System suitability 
Sample:  Standard solution
Suitability requirements 
Relative standard deviation:  NMT 2.0%
Analysis 
Samples:  Standard solution and Sample solution
Calculate the percentage of deferoxamine mesylate (C25H48N6O8·CH4O3S) in the portion of Deferoxamine Mesylate taken:
Result = (rU/rS) × (CS/CU) × 100
rU== peak response of deferoxamine from the Sample solution
rS== peak response of deferoxamine from the Standard solution
CS== concentration of the Standard solution (mg/mL)
CU== concentration of the Sample solution (mg/mL)
Acceptance criteria:  93.0%(RB 1-May-2011)–102.0% on the anhydrous basis
IMPURITIES
•  Residue on Ignition 281: NMT 0.1%, 2.0 g being used
•  Chloride and Sulfate, Chloride 221: A 1.2-g portion shows no more chloride than corresponds to 0.20 mL of 0.020 N hydrochloric acid (NMT 0.012%).
•  Chloride and Sulfate, Sulfate 221: A 0.5-g portion shows no more sulfate than corresponds to 0.20 mL of 0.020 N sulfuric acid (NMT 0.04%).
•  Heavy Metals, Method II 231: NMT 10 ppm
Change to read:
•  Organic Impurities
Solution A, Solution B, Diluent, Mobile phase, Sample solution, and Chromatographic system:  Proceed as directed in the Assay.
Standard stock solution:  Use the Standard solution, prepared as directed in the Assay. [Note—USP Deferoxamine Mesylate RS contains impurity A as a minor component. ]
Standard solution:  0.01 mg/mL of USP Deferoxamine Mesylate RS in Diluent from the Standard stock solution
System suitability 
Samples:  Standard stock solution and Standard solution
Suitability requirements 
Resolution:  NLT 2.0 between the impurity A and deferoxamine peaks, Standard stock solution
Relative standard deviation:  NMT 5.0% for the deferoxamine peak, Standard solution
Analysis 
Samples:  Standard solution and Sample solution
Calculate the percentage of each impurity in the portion of Deferoxamine Mesylate taken:
Result = (rU/rS) × (CS/CU) × 100
rU== peak response of each impurity from the Sample solution
rS== peak response of deferoxamine from the Standard solution
CS== concentration of the Standard solution (mg/mL)
CU== concentration of the Sample solution (mg/mL)
Acceptance criteria:  See Table 2.
[Note—The reporting level for impurities is 0.04%. ]
Table 2
Name Relative
Retention
Time
Acceptance
Criteria,
NMT (%)
Impurity A* 0.85 3.0(RB 1-May-2011)
Deferoxamine 1.0
Any unspecified impurity 1.0
Total impurities eluting before deferoxamine(RB 1-May-2011) 5.0
Total impurities eluting after deferoxamine(RB 1-May-2011) 2.0(RB 1-May-2011)
*  Des-methylene impurity (desferrioxamine A1).
SPECIFIC TESTS
•  pH 791: 4.0–6.0, in a solution (1 in 100)
•  Sterility Tests 71: Where the label states that Deferoxamine Mesylate is sterile, it meets the requirements.
•  Bacterial Endotoxins Test 85: Where the label states that Deferoxamine Mesylate is sterile or must be subjected to further processing during the preparation of injectable dosage forms, it contains NMT 0.33 USP Endotoxin Unit/mg of deferoxamine mesylate.
ADDITIONAL REQUIREMENTS
•  Packaging and Storage: Preserve in tight containers. Store in a cold place.
•  Labeling: Where it is intended for use in preparing injectable dosage forms, the label states that it is sterile or must be subjected to further processing during the preparation of injectable dosage forms.
•  USP Reference Standards 11
USP Deferoxamine Mesylate RS Click to View Structure
USP Endotoxin RS
Auxiliary Information— Please check for your question in the FAQs before contacting USP.
Topic/Question Contact Expert Committee
Monograph Elena Gonikberg, Ph.D.
Principal Scientific Liaison
1-301-816-8251
(SM32010) Monographs - Small Molecules 3
71 Radhakrishna S Tirumalai, Ph.D.
Principal Scientific Liaison
1-301-816-8339
(GCM2010) General Chapters - Microbiology
85 Radhakrishna S Tirumalai, Ph.D.
Principal Scientific Liaison
1-301-816-8339
(GCM2010) General Chapters - Microbiology
Reference Standards RS Technical Services
1-301-816-8129
rstech@usp.org
USP35–NF30 Page 2813
Pharmacopeial Forum: Volume No. 35(4) Page 847