Iron Dextran Injection

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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To view the Notice from the Expert Committee that posted in conjunction with this accelerated revision, please click www.uspnf.com/rb-iron dextran-inj-20231027. 

1 DEFINITION 

Iron Dextran Injection is a sterile, colloidal solution of ferric hydroxide in complex with partially hydrolyzed Dextran of low molecular weight, in Water for Injection. It contains NLT 95.0% and NMT 105.0% of the labeled amount of iron. It may contain NMT 0.5% of phenol as a preservative. 

2 IDENTIFICATION 

To 1 mL of Injection on a watch glass add 2 drops of ammonium hydroxide. No precipitate is formed. Add 2 mL of hydrochloric acid, and add 2 mL of ammonium hydroxide. A brown precipitate is formed. 

3 ASSAY 

Procedure for Iron 

Solution A: Transfer 2.64 g of calcium chloride dihydrate to a 1000-mL volumetric flask. Add 500 mL of water, and swirl to dissolve. Add 5.0 mL of hydrochloric acid, and dilute with water to volume. 

Standard stock solution: 50 µg/mL of iron prepared as follows. Transfer 350 mg of ferrous ammonium sulfate hexahydrate to a 1000-mL volumetric flask. Add water to dissolve, dilute with water to volume, and mix. 

Standard solutions: 1.0, 2.0, 3.0, 4.0, and 5.0 µg/mL of iron from Standard stock solution prepared as follows. To separate 100-mL volumetric flasks transfer 2.0, 4.0, 6.0, 8.0, and 10.0 mL, respectively, of Standard stock solution. Dilute the contents in each flask with Solution A to volume, and mix. 

Sample stock solution: Nominally equivalent to 0.5 mg/mL of iron prepared as follows. Using a “to contain” pipet, transfer a volume of Injection, nominally equivalent to 100 mg of iron, to a 200-mL volumetric flask. Dilute with Solution A to volume, and mix. Sample solution: Nominally equivalent to 4 µg/mL of iron in Solution A from Sample stock solution prepared as follows. Transfer 2.0 mL of Sample stock solution to a 250-mL volumetric flask, and dilute with Solution A to volume. 

Instrumental conditions 

(See Atomic Absorption Spectroscopy 〈852〉.) 

Mode: Atomic absorption 

Analytical wavelength: Iron emission line of 248.3 nm 

Lamp: Iron hollow-cathode 

Flame: Air–acetylene 

Blank: Solution A 

Analysis 

Samples: Standard solutions and Sample solution 

Plot the absorbance of each of the Standard solutions versus concentration, in µg/mL, of iron, and draw the straight line best tting the ve plotted points. From the graph so obtained, determine the concentration of iron, in µg/mL, in the Sample solution, C_A 

Calculate the percentage of the labeled amount of iron in the portion of Injection taken: 

Result = (C_A/C_T) × 100 

C_A = concentration of iron in the Sample solution, determined from the standard calibration graph (µg/mL) 

C_T = nominal concentration of the Sample solution (µg/mL) 

Acceptance criteria: 95.0%–105.0% 

4 OTHER COMPONENTS 

Antimicrobial Agents—Content, Phenol 〈341〉: NMT 0.5% 

5 IMPURITIES 

Content of Chloride 

Sample: Using a “to contain” pipet, transfer 10.0 mL of Injection to a 150-mL beaker, rinsing the pipet into the beaker with several small portions of water. Add 50 mL of water and 2 mL of nitric acid.

Titrimetric system 

Mode: Direct titration 

Titrant: 0.1 N silver nitrate VS 

Endpoint detection: Potentiometric 

Analysis: Titrate with Titrant determining the endpoint potentiometrically using silver–glass electrodes. Each mL of Titrant consumed is equivalent to 3.545 mg of chloride (Cl). 

Acceptance criteria 

For products labeled to contain 50 mg/mL of iron: 0.48%–0.68% 

For products labeled to contain 75 or 100 mg/mL of iron: 0.8%–1.1% 

Nonvolatile Residue 

Sample solution: Using a “to contain” pipet, transfer 1.0 mL of Injection onto 3–5 g of sand spread in a shallow layer in a stainless steel dish, the dish and sand having been previously dried and weighed. Rinse the pipet, with several small portions of water, onto the sand. Analysis: Evaporate the Sample solution on a steam bath to dryness, continue the drying in an oven at 105° for 15 h, and weigh. Acceptance criteria 

For products labeled to contain 50 mg/mL of iron: 28.0%–32.0% 

For products labeled to contain 75 mg/mL of iron: 35.0%–40.0% 

For products labeled to contain 100 mg/mL of iron: 37.0%–43.0% 

6 SPECIFIC TESTS 

pH 〈791〉: 4.5–7.0 

Bacterial Endotoxins Test 〈85〉: NMT 0.50 USP Endotoxin Units/mg of iron 

Delete the following: 

Acute Toxicity 

Absorption from Injection Site 

Analysis: Prepare a site over the semitendinosus muscle of one leg of each of two rabbits by clipping the fur and disinfecting the exposed skin. Inject each site with a dose of 0.4 mL/kg of body weight in the following manner. Place the needle in the distal end of the semitendinosus muscle at an angle such as to ensure that the full length of the needle is used, then pass it through the sartorius and vastus medialis muscles. House the rabbits separately. Seven days after the injection, sacrifice the rabbits, and dissect the treated legs to examine the muscles. 

Acceptance criteria: No heavy black deposit of unabsorbed iron compounds is observed, and the tissue is only lightly colored. Other Requirements: Meets the requirements in Injections and Implanted Drug Products 〈1〉 

7 ADDITIONAL REQUIREMENTS 

Packaging and Storage: Preserve in single-dose or multiple-dose containers, preferably of Type I or Type II glass.