Ferrous Gluconate
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This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition
Issued and maintained by the United States Pharmacopeial Convention (USP)
C12H22FeO14 · 2H2O 482.17
d-Gluconic acid, iron(2+) salt (2:1), dihydrate;
Iron(2+) gluconate (1:2) dihydrate CAS RN®: 12389-15-0.
Anhydrous 446.15 CAS RN®: 299-29-6.
1 DEFINITION
Ferrous Gluconate contains NLT 97.0% and NMT 102.0% of ferrous gluconate (C12H22FeO14), calculated on the dried basis.
2 IDENTIFICATION
2.1 A. Thin-Layer Chromatography
Standard solution: 10 mg/mL of USP Potassium Gluconate RS
Sample solution: 10 mg/mL of Ferrous Gluconate, heating in a water bath at 60°, if necessary, to dissolve
2.1.1 Chromatographic system
(See Chromatography 〈621〉, Thin-Layer Chromatography.)
Mode: TLC
Adsorbent: 0.25-mm layer of chromatographic silica gel
Application volume: 5 µL
Developing solvent system: Alcohol, ethyl acetate, ammonium hydroxide, and water (50:10:10:30)
Spray reagent: Dissolve 2.5 g of ammonium molybdate in 50 mL of 2 N sulfuric acid in a 100-mL volumetric ask, add 1.0 g of ceric sulfate, swirl to dissolve, and dilute with 2 N sulfuric acid to volume.
2.1.2 Analysis
Samples: Standard solution and Sample solution
Develop the chromatogram until the solvent front has moved about three-fourths of the length of the plate. Remove the plate from the chamber, and dry at 110° for 20 min. Allow to cool, and spray with Spray reagent. Heat the plate at 110° for about 10 min. Acceptance criteria: The principal spot of the Sample solution corresponds in color, size, and R value to that of the Standard solution. F
2.2 B. Ferrous Ion
Sample solution: 5 mg/mL in water
Analysis: Add potassium ferricyanide TS to the Sample solution.
Acceptance criteria: The solution yields a dark blue precipitate.
3 ASSAY
Procedure
Sample: 1.5 g of Ferrous Gluconate
Blank: Proceed as directed in the Analysis without the Sample.
Titrimetric system
(See Titrimetry 〈541〉.)
Mode: Direct titration
Titrant: 0.1 N ceric sulfate VS
Endpoint detection: Visual
Analysis: Dissolve the Sample in a mixture of 75 mL of water and 15 mL of 2 N sulfuric acid in a 300-mL conical ask. Add 250 mg of zinc dust, close the ask with a stopper containing a Bunsen valve, and allow to stand at room temperature for 20 min or until the solution becomes colorless. Pass the solution through a filtering crucible containing a thin layer of zinc dust, and wash the crucible and contents with 10 mL of 2 N sulfuric acid, followed by 10 mL of water. [Note—Prepare and use the filtering crucible in a well-ventilated hood.] Add orthophenanthroline TS, and immediately titrate the filtrate in the suction ask with Titrant. Perform a blank determination. Calculate the percentage of ferrous gluconate (C12H22FeO14) in the Sample taken:
Result = {[(VS − VB ) × N × F]/W} × 100
VS = Titrant volume consumed by the Sample (mL)
VB = Titrant volume consumed by the Blank (mL)
N = Titrant normality (mEq/mL)
F = equivalency factor, 446.2 mg/mEq
W = Sample weight (mg)
Acceptance criteria: 97.0%–102.0% on the dried basis
4 IMPURITIES
4.1 Chloride and Sulfate, Chloride〈221〉
Standard solution: 1.0 mL of 0.020 N hydrochloric acid
Sample: 1.0 g
Acceptance criteria: NMT 0.07%
Chloride and Sulfate, Sulfate〈221〉
Standard solution: 1.0 mL of 0.020 N sulfuric acid
Sample: 1.0 g
Acceptance criteria: NMT 0.1%
4.2 Mercury 〈261〉
NMT 3 ppm
Change to read:
4.3 Arsenic 〈211〉
Procedures, Procedure 1 (CN 1-Jun-2023)
Test preparation: Transfer 1.0 g of Ferrous Gluconate to a 100-mL round-bottom ask fitted with a 24/40 standard-taper joint. Add 40 mL of 9 N sulfuric acid and 2 mL of potassium bromide solution (3 in 10). Immediately connect to a suitable distillation apparatus that has a reservoir with a water jacket, cooled with circulating ice water, and heat to dissolve the Ferrous Gluconate. Distill, collect 25 mL of distillate, and transfer the distillate to the arsine generator ask. Wash the condenser and reservoir several times with small portions of water, add the washings to the distillate in the generator ask, add bromine TS until the solution is slightly yellow, and dilute with water to 35 mL. Proceed as directed in the chapter.
Acceptance criteria: NMT 3 ppm
4.4 Limit of Lead
[Note—For the preparation of all aqueous solutions and for the rinsing of glassware before use, use water that has been passed through a strong-acid, strong-base, mixed-bed ion-exchange resin before use. Select all reagents to have as low a content of lead as practicable, and store all reagent solutions in containers of borosilicate glass. Cleanse glassware before use by soaking in warm 8 N nitric acid for 30 min and by rinsing with deionized water.]
Ascorbic acid–sodium iodide solution: 100 mg/mL of ascorbic acid and 192.5 mg/mL of sodium iodide
Trioctylphosphine oxide solution: 50 mg/mL of trioctylphosphine oxide in 4-methyl-2-pentanone. [Caution—This solution causes irritation. Avoid contact with eyes, skin, and clothing. Take special precautions in disposing of unused portions of solutions to which this reagent is added.]
Standard solution: Transfer 5.0 mL of lead nitrate stock solution TS to a 100-mL volumetric ask, and dilute with water to volume. Transfer 2.0 mL of the resulting solution to a 50-mL volumetric ask, add 10 mL of 9 N hydrochloric acid and 10 mL of water. Add 20 mL of Ascorbic acid–sodium iodide solution and 5.0 mL of Trioctylphosphine oxide solution, shake for 30 s, and allow to separate. Add water to bring the organic solvent layer into the neck of the ask, shake again, and allow to separate. The organic layer is the Standard solution, and it contains 2 µg/mL of lead.
Sample solution: To a 50-mL volumetric ask add 1.0 g of Ferrous Gluconate, 10 mL of 9 N hydrochloric acid, 10 mL of water, 20 mL of Ascorbic acid–sodium iodide solution, and 5.0 mL of Trioctylphosphine oxide solution. Shake for 30 s, and allow to separate. Add water to bring the organic solvent layer into the neck of the ask, shake again, and allow to separate. The organic layer is the Sample solution.
Blank: To a 50-mL volumetric ask add 10 mL of 9 N hydrochloric acid, 10 mL of water, 20 mL of Ascorbic acid–sodium iodide solution, and 5.0 mL of Trioctylphosphine oxide solution. Shake for 30 s, and allow to separate. Add water to bring the organic solvent layer into the neck of the ask, shake again, and allow to separate. The organic layer is the Blank, and it contains 0 µg/mL of lead.
4.4.1 Instrumental conditions
(See Atomic Absorption Spectroscopy 〈852〉.)
Mode: Atomic absorption spectrophotometry
Analytical wavelength: 283.3 nm
Lamp: Lead hollow-cathode
Flame: Air–acetylene
4.4.2 System suitability
Samples: Standard solution and Blank
Suitability requirements: The absorbance of the Standard solution and the absorbance of the Blank are significantly different.
4.4.3 Analysis
Samples: Standard solution, Sample solution, and Blank Concomitantly determine the absorbances of the Blank, Standard solution, and Sample solution. Use the Blank to set the instrument to zero.
Acceptance criteria: The absorbance of the Sample solution does not exceed that of the Standard solution (NMT 10 ppm).
4.5 Limit of Ferric Iron
Sample: 5 g of Ferrous Gluconate
Blank: Proceed as directed in the Analysis without the Sample.
Titrimetric system
(See Titrimetry 〈541〉.)
Mode: Direct titration
Titrant: 0.1 N sodium thiosulfate VS
Endpoint detection: Visual
Analysis: Dissolve the Sample in a mixture of 100 mL of water and 10 mL of hydrochloric acid, and add 3 g of potassium iodide. Shake, and allow to stand in the dark for 5 min. Titrate any liberated iodine with the Titrant, adding 3 mL of starch TS as the endpoint is approached. Perform a blank determination.
Calculate the percentage of ferric iron in the portion of Ferrous Gluconate taken:
Result = {[(VS − VB ) × N × F]/W} × 100
VS = Titrant volume consumed by the Sample (mL)
VB = Titrant volume consumed by the Blank (mL)
N = Titrant normality (mEq/mL)
F = equivalency factor, 55.85 mg/mEq
W = Sample weight (mg)
Acceptance criteria: NMT 2.0%
4.6 Oxalic Acid
Sample: 1.0 g
Analysis: Dissolve the Sample in 10 mL of water, add 2 mL of hydrochloric acid, and transfer to a separator. Extract successively with 50 mL and 20 mL of ether. Combine the ether extracts, add 10 mL of water, and evaporate the ether on a steam bath. Add 1 drop of 6 N acetic acid and 1 mL of a 50 mg/mL solution of calcium acetate.
Acceptance criteria: No turbidity is produced within 5 min.
4.7 Reducing Sugars
Sample: 500 mg
Analysis: Dissolve the Sample in 10 mL of water, warm, and render alkaline with 1 mL of 6 N ammonium hydroxide. Pass hydrogen sulfide gas into the solution to precipitate the iron, and allow the solution to stand for 30 min to coagulate the precipitate. Filter, and wash the precipitate with two successive 5-mL portions of water. Acidify the combined filtrate and washings with hydrochloric acid, and add 2 mL of 3 N hydrochloric acid in excess. Boil the solution until the vapors no longer darken lead acetate paper, and continue to boil, if necessary, until it has been concentrated to 10 mL. Cool, add 5 mL of sodium carbonate TS and 20 mL of water, filter, and adjust the volume of the filtrate to 100 mL. To 5 mL of the filtrate add 2 mL of alkaline cupric tartrate TS, and boil for 1 min.
Acceptance criteria: No red precipitate is formed within 1 min.
5 SPECIFIC TESTS
Loss on Drying 〈731〉
Analysis: Dry at 105° for 16 h.
Acceptance criteria: 6.5%—10.0%
6 ADDITIONAL REQUIREMENTS
Packaging and Storage: Preserve in tight containers.
USP Reference Standards 〈11〉
USP Potassium Gluconate RS.
