Ferrous Gluconate Tablets

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3178 Ferrous / Official Monographs USP 35

• USP REFERENCE STANDARDS 〈11〉 W = nominal amount of ferrous gluconate dihydrate USP Potassium Gluconate RS in the Sample taken (mg) Acceptance criteria: 94.0%–106.0% OTHER COMPONENTS

. • ALCOHOL DETERMINATION 〈611〉: 6.3%–7.7% of C 2H5OH Ferrous Gluconate Oral Solution SPECIFIC TESTS • PH 〈791〉: 3.4–3.8 DEFINITION Ferrous Gluconate Oral Solution contains NL T 94.0% and NMT ADDITIONAL REQUIREMENTS 106.0% of the labeled amount of ferrous gluconate dihydrate • PACKAGING AND STORAGE: Preserve in tight, light-resistant (C12H22FeO14 · 2H2O). containers. • LABELING: Label the Oral Solution in terms of the content of IDENTIFICATION ferrous gluconate dihydrate (C 12H22FeO14 · 2H2O) and in • A. THIN-LAYER CHROMATOGRAPHY terms of the content of elemental iron. Standard solution: 10 mg/mL of USP Potassium Gluconate • USP REFERENCE STANDARDS 〈11〉 RS in water USP Potassium Gluconate RS Sample solution: A filtered solution in water, equivalent to 10 mg/mL of ferrous gluconate dihydrate from Oral Solution Chromatographic system

(See Chromatography 〈621〉, Thin-Layer Chromatography.) . Mode: TLC Adsorbent: 0.25-mm layer of chromatographic silica gel Ferrous Gluconate Tablets Application volume: 5 µL Developing solvent system: Alcohol, ethyl acetate, ammo- DEFINITION nium hydroxide, and water (50:10:10:30) Ferrous Gluconate Tablets contain NLT 93.0% and NMT Spray reagent: Dissolve 2.5 g of ammonium molybdate in 107.0% of the labeled amount of ferrous gluconate dihydrate 50 mL of 2 N sulfuric acid in a 100-mL volumetric flask. (C12H22FeO14 · 2H2O). Add 1.0 g of ceric sulfate, swirl to dissolve, and dilute with IDENTIFICATION 2 N sulfuric acid to volume. • A. THIN-LAYER CHROMATOGRAPHY Analysis Standard solution: 10 mg/mL of USP Potassium Gluconate Samples: Standard solution and Sample solution RS Develop the chromatogram until the solvent front has Sample solution: A filtered solution in water, equivalent to moved about three-fourths of the length of the plate. Re- 10 mg/mL of ferrous gluconate dihydrate from powdered move the plate from the chamber, and dr y at 110° for 20 Tablets min. Allow to cool, and spray with Spray reagent. Heat the Chromatographic system plate at 110° for about 10 min. (See Chromatography 〈621〉, Thin-Layer Chromatography.) Acceptance criteria: The principal spot of the Sample solu- Mode: TLC tion corresponds in color, size, and RF value to that of the Adsorbent: 0.25-mm layer of chromatographic silica gel Standard solution. Application volume: 5 µL • B. FERROUS ION Developing solvent system: Alcohol, ethyl acetate, ammo- Sample solution: Equivalent to 5 mg/mL of ferrous gluco- nium hydroxide, and water (50:10:10:30) nate dihydrate from a dilution in water of the Sample solu- Spray reagent: Dissolve 2.5 g of ammonium molybdate in tion obtained in Identification test A 50 mL of 2 N sulfuric acid in a 100-mL volumetric flask. Analysis: Add potassium ferricyanide TS to the Sample Add 1.0 g of ceric sulfate, swirl to dissolve, and dilute with solution. 2 N sulfuric acid to volume. Acceptance criteria: The solution yields a dark blue Analysis precipitate. Samples: Standard solution and Sample solution ASSAY Develop the chromatogram until the solvent front has moved about three-fourths of the length of the plate. Re- • PROCEDURE Sample: An accurately measured volume of Oral Solution, move the plate from the chamber, and dr y at 110° for 20 equivalent to 1.2 g of ferrous gluconate dihydrate min. Allow to cool, and spray with Spray reagent. Heat the Blank: Proceed as directed in the Analysis without the plate at 110° for about 10 min. Sample. Acceptance criteria: The principal spot of the Sample solu- Titrimetric system tion corresponds in color, size, and RF value to that of the Standard solution. (See Titrimetry 〈541〉.) Mode: Direct titration • B. FERROUS ION Titrant: 0.1 N ceric sulfate VS Sample solution: Equivalent to 5 mg/mL of ferrous gluco- Indicator: Orthophenanthroline TS nate dihydrate from a dilution of the Sample solution ob- Endpoint detection: Visual tained in Identification test A Analysis: Dissolve the Sample in a cooled mixture of 80 mL Analysis: Add potassium ferricyanide TS to the Sample of recently boiled water and 80 mL of 2 N sulfuric acid. Add solution. orthophenanthroline TS, and immediately titrate with Titrant Acceptance criteria: The solution yields a dark blue until a change in color. Per form a Blank determination. precipitate. Calculate the per centage of the labeled amount of ferrous ASSAY gluconate dihydrate (C 12H22FeO14 · 2H2O) in the portion of • PROCEDURE Oral Solution taken: Sample: A portion of the powder from NL T 20 finely powdered Tablets, equivalent to 1.5 g of ferrous gluconate Result = {[(VS − VB) × N × F]/W} × 100 dihydrate Blank: Proceed as directed in the Analysis without the VS = Titrant volume consumed by the Sample (mL) Sample. VB = Titrant volume consumed by the Blank (mL) N = actual normality of the Titrant (mEq/mL) Titrimetric system F = equivalency factor, 482.2 mg/mEq (See Titrimetry 〈541〉.)

USP 35 Official Monographs / Ferrous 3179

Mode: Direct titration • USP REFERENCE STANDARDS 〈11〉 Titrant: 0.1 N ceric sulfate VS USP Potassium Gluconate RS Indicator: Orthophenanthroline TS 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 flask. . Add 250 mg of zinc dust, close the flask with a stopper Ferrous Sulfate containing a Bunsen valve, and allow to stand at room tem- perature for 20 min or until the solution becomes colorless. FeSO4 · 7H2O 278.02 Pass the solution through a filtering crucible containing a thin layer of zinc dust, and wash the crucible and contents FeSO4 151.91 with 10 mL of 2 N sulfuric acid, followed by 10 mL of water. Sulfuric acid, iron(2+) salt (1:1), heptahydrate; [NOTE—Prepare and use the filtering crucible in a well-ven- Iron(2+) sulfate (1:1) heptahydrate [7782-63-0]. tilated hood.] Anhydrous [7720-78-7]. Add orthophenanthroline TS, and immediately titrate the fil- trate in the suction flask with Titrant until color change. DEFINITION Perform a Blank determination. Ferrous Sulfate contains an amount of anhydrous ferrous sulfate Calculate the percentage of the labeled amount of ferrous (FeSO4) equivalent to NL T 99.5% and NMT 104.5% of ferrous sulfate heptahydrate (FeSO 4 · 7H2O). gluconate dihydrate (C 12H22FeO14 · 2H2O) in the portion of Tablets taken: IDENTIFICATION • A. IDENTIFICATION TESTS—GENERAL, Iron, Ferrous Salts 〈191〉 Result = {[(VS VB) N F]/W} 100 − × × × and Sulfate 〈191〉: Meets the requirements VS = Titrant volume consumed by the Sample (mL) ASSAY VB = Titrant volume consumed by the Blank (mL) • PROCEDURE N = actual normality of the Titrant (mEq/mL) Sample: 1 g of Ferrous Sulfate F = equivalency factor, 482.2 mg/mEq Blank: Proceed as in the Analysis without the Sample. W = nominal amount of ferrous gluconate dihydrate Titrimetric system in the Sample taken (mg) (See Titrimetry 〈541〉.) Acceptance criteria: 93.0%–107.0% Mode: Direct titration PERFORMANCE TESTS Titrant: 0.1 N ceric sulfate VS Endpoint detection: Visual • DISSOLUTION 〈711〉 Medium: Simulated gastric fluid TS; 900 mL Analysis: Dissolve the Sample in a mixture of 25 mL of 2 N Apparatus 2: 150 rpm sulfuric acid and 25 mL of freshly boiled and cooled water. Time: 80 min Add orthophenanthroline TS, and immediately titrate with Standard solution: Solution having a known concentration Titrant. Perform a blank determination. of iron in the Medium Calculate the per centage of ferrous sulfate heptahydrate Sample solution: Filtered portion of the solution under test, (FeSO4 · 7H2O) in the Sample taken: suitably diluted with the Medium if necessar y Result = {[(VS − VB) × N × F]/W} × 100 Instrumental conditions (See Spectrophotometry and Light-Scattering 〈851〉.) VS = Titrant volume consumed by the Sample (mL) Mode: Atomic absorption spectrophotometr y VB = Titrant volume consumed by the Blank (mL) Analytical wavelength: 248.3 nm N = Titrant normality (mEq/mL) Lamp: Iron hollow-cathode F = equivalency factor, 278.0 mg/mEq Flame: Air–acetylene W = Sample weight (mg) Analysis Acceptance criteria: 99.5%–104.5% of ferrous sulfate Samples: Standard solution and Sample solution heptahydrate Determine the concentration of iron (Fe) in the Sample solution in comparison with a Standard solution. IMPURITIES Calculate the percentage of the labeled amount of ferrous • ARSENIC, Method I 〈211〉 gluconate dihydrate (C 12H22FeO14 · 2H2O) dissolved: Test preparation: Transfer 1 g of Ferrous Sulfate to a round- bottomed, 100-mL flask fitted with a glass joint, and add 40 Result = (Mr/Ar) × (C × D × V/L) × 100 mL of sulfuric acid (1 in 4) and 2 mL of 300 mg/mL potassium bromide solution. Immediately connect the flask Mr = molecular weight of ferrous gluconate dihydrate, to a condenser having a matching glass joint and a reser voir 482.17 with a water jacket that is cooled by ice water. Heat the Ar = atomic weight of iron, 55.85 flask gently over a low flame until the solid dissolves, then C = measured concentration of iron in the Sample distill until 25 mL of distillate collects in the reser voir. solution (mg/mL) Transfer this distillate to the arsine generator flask, and wash D = dilution factor for the Sample solution the condenser and the reser voir with several small portions V = volume of Medium, 900 mL of water, adding the washings to the generator flask. Swirl L = label amount of ferrous gluconate dihydrate to mix, add bromine TS until the color of the solution is (mg/Tablet) slightly yellow, and dilute with water to 35 mL. Tolerances: NLT 80% (Q) of the labeled amount of ferrous Acceptance criteria: NMT 3 ppm gluconate dihydrate (C 12H22FeO14 · 2H2O) is dissolved. • LEAD • UNIFORMITY OF DOSAGE UNITS 〈905〉: Meet the requirements [NOTE—For the preparation of all aqueous solutions and for ADDITIONAL REQUIREMENTS the rinsing of glassware before use, use water that has been passed through a strong-acid, strong-base, mixed-bed • PACKAGING AND STORAGE: Preserve in tight containers. ion-exchange resin. Select all reagents to have as low a • LABELING: Label the Tablets in terms of the content of ferrous content of lead as practicable, and store all reagent gluconate dihydrate (C 12H22FeO14 · 2H2O) and in terms of the content of elemental iron. solutions in containers of borosilicate glass. Cleanse glassware before use by soaking in warm nitric acid (1 in 2) for 30 min and by rinsing with deionized water.]