Ferrous Fumarate
;)
2-Butenedioic acid,(E)-,iron(2+)salt.
Iron(2+)fumarate [141-01-5].
»Ferrous Fumarate contains not less than 97.0percent and not more than 101.0percent of C4H2FeO4,calculated on the dried basis.
Packaging and storage—
Preserve in well-closed containers.
Identification—
A:
To 1.5g add 25mLof dilute hydrochloric acid (1in 2).Dilute with water to 50mL,heat to dissolve,then cool,filter on a fine-porosity,sintered-glass crucible,wash the precipitate with dilute hydrochloric acid (3in 100),saving the filtrate for Identificationtest B,and dry the precipitate at 105
:the IRabsorption of a potassium bromide dispersion of the dried precipitate so obtained exhibits maxima only at the same wavelengths as that of a similar preparation of USP Fumaric Acid RS.
:the IRabsorption of a potassium bromide dispersion of the dried precipitate so obtained exhibits maxima only at the same wavelengths as that of a similar preparation of USP Fumaric Acid RS.
B:
Aportion of the filtrate obtained in the preceding test responds to the tests for Iron á191ñ.
Loss on drying á731ñ—
Dry it at 105for 16hours:it loses not more than 1.5%of its weight.
for 16hours:it loses not more than 1.5%of its weight.
Sulfate—
Transfer 1.0g to a 250-mLbeaker,add 100mLof water,and heat on a steam bath,adding hydrochloric acid dropwise,until complete solution is effected (about 2mLof the acid will be required).Filter the solution if necessary,and dilute the filtrate with water to 100mL.Heat the filtrate to boiling,add 10mLof barium chloride TS,warm on a steam bath for 2hours,cover,and allow to stand for 16hours.(If crystals of ferrous fumarate form,warm the solution on the steam bath to dissolve them.)Pass the solution through ashless filter paper,wash the residue with hot water until,with the addition of ammonium sulfide TS,a black precipitate is no longer formed in the filtrate,and transfer the paper containing the residue to a tared crucible.Char the paper,without burning,and ignite the crucible and its contents at 600to constant weight:each mg of residue is equivalent to 0.412mg of SO4.Not more than 0.2%is found.
to constant weight:each mg of residue is equivalent to 0.412mg of SO4.Not more than 0.2%is found.
Arsenic,Method Iá211ñ—
Transfer 2.0g to a beaker,and add 10mLof water and 10mLof sulfuric acid.Warm to precipitate the fumaric acid completely,cool,add 30mLof water,and filter into a 100-mLvolumetric flask.Wash the precipitate with water,adding the washings to the flask,add water to volume,and mix.Transfer 50.0mLof this solution into the arsine generator flask,and dilute with water to 55mL:the resulting solution meets the requirements of the test,the addition of 20mLof 7Nsulfuric acid specified for Procedurebeing omitted.The limit is 3ppm.
Limit of ferric iron—
Transfer 2.0g,accurately weighed,to a glass-stoppered,250-mLconical flask,add 25mLof water and 4mLof hydrochloric acid,and heat on a hot plate until solution is complete.Insert the stopper in the flask,and cool to room temperature.Add 3g of potassium iodide,insert the stopper in the flask,swirl to mix,and allow to stand in the dark for 5minutes.Remove the stopper,add 75mLof water,and titrate with 0.1Nsodium thiosulfate VS,adding 3mLof starch TSas the end-point is approached.Not more than 7.16mLof 0.1Nsodium thiosulfate is consumed (2.0%).
Limit of lead—
[NOTE—For the preparation of all aqueous solutions and for the rinsing of glassware before use,employ 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.Clean glassware before use by soaking in warm 8Nnitric acid for 30minutes and by rinsing with deionized water.]
Ascorbic acid–sodium iodide solution—
Dissolve 20g of ascorbic acid and 38.5g of sodium iodide in water in a 200-mLvolumetric flask,dilute with water to volume,and mix.
Trioctylphosphine oxide solution—
[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.
]Dissolve 5.0g of trioctylphosphine oxide in 4-methyl-2-pentanone in a 100-mLvolumetric flask,dilute with the same solvent to volume,and mix.
Standard solution and Blank—
Transfer 5.0mLof Lead Nitrate Stock Solution,prepared as directed in the test for Heavy Metals á231ñ,to a 100-mLvolumetric flask,dilute with water to volume,and mix.Transfer 2.0mLof the resulting solution to a 50-mLbeaker.To this beaker and to a second,empty beaker(Blank)add 6mLof nitric acid and 10mLof perchloric acid,and evaporate in a hood to dryness.[Caution—Use perchloric acid in a well-ventilated fume hood with proper precautions.
]Cool,dissolve the residues in 10mLof 9Nhydrochloric acid,and transfer with the aid of about 10mLof water to separate 50-mLvolumetric flasks.To each flask add 20mLof Ascorbic acid–sodium iodide solutionand 5.0mLof Trioctylphosphine oxide solution,shake for 30seconds,and allow to separate.Add water to bring the organic solvent layer into the neck of each flask,shake again,and allow to separate.The organic solvent layers are the Blankand the Standard solution,and they contain 0.0and 2.0µg of lead per mL,respectively.
Test solution—
Add 1.0g of Ferrous Fumarate to a 50-mLbeaker,and add 6mLof nitric acid and 10mLof perchloric acid.[Caution—Use perchloric acid in a well-ventilated fume hood with proper precautions.
]Cover with a ribbed watch glass,and heat in a hood until completely dry.Cool,dissolve the residue in 10mLof 9Nhydrochloric acid,and transfer with the aid of about 10mLof water to a 50-mLvolumetric flask.Add 20mLof Ascorbic acid–sodium iodide solutionand 5.0mLof Trioctylphosphine oxide solution,shake for 30seconds,and allow to separate.Add water to bring the organic solvent layer into the neck of the flask,shake again,and allow to separate.The organic solvent layer is the Test solution.
Procedure—
Concomitantly determine the absorbances of the Blank,Standard solution,and Test solutionat the lead emission line at 283.3nm with a suitable atomic absorption spectrophotometer (see Spectrophotometry and Light-scattering á851ñ)equipped with a lead hollow-cathode lamp and an air–acetylene flame,using the blank to set the instrument to zero.In a suitable analysis,the absorbance of the Standard solutionand the absorbance of the Blank are significantly different:the absorbance of the Test solutiondoes not exceed that of the Standard solution(0.001%).
Mercury—
[NOTES—(1)Carry out this procedure in subdued light,since mercuric dithizonate is light-sensitive.(2)For preparation of solutions,see Mercury á261ñ.]Dissolve about 1g,accurately weighed,in 30mLof dilute nitric acid (1in 10),with the aid of heat,on a steam bath.Cool quickly by immersion in an ice bath,and pass through a fine-porosity filter that previously has been washed with dilute nitric acid (1in 10)and water.To the filtrate add 20mLof sodium citrate solution (1in 4)and 1mLof Hydroxylamine Hydrochloride Solution.
Prepare a control solution consisting of 3.0mLof Standard Mercury Solution,30mLof dilute nitric acid (1in 10),5mLof sodium citrate solution (1in 4),and 1mLof Hydroxylamine Hydrochloride Solution.
Using ammonium hydroxide,adjust the control solution to a pHof 1.8,determined potentiometrically,and transfer to a separator.Using sulfuric acid,adjust the test solution to a pHof 1.8,determined potentiometrically,and transfer to a separator.Treat the solution under test and the control solution in parallel as follows.Extract with two 5-mLportions of Dithizone Extraction Solutionand 5mLof chloroform,pooling the chloroform extracts in a second separator.Add 10mLof dilute hydrochloric acid (1in 2),shake,allow the layers to separate,and discard the chloroform layer.Wash the acid extract with 3mLof chloroform,and discard the washing.Add 0.1mLof edetate disodium solution (1in 50)and 2mLof 6Nacetic acid,mix,and add slowly 5mLof ammonium hydroxide.Close the separator,cool it under cold running water,and dry its outer surface.Remove the stopper,and pour the contents into a beaker.Adjust the solution under test and the control solution to a pHof 1.8in the same manner as before,and return the solutions to their respective separators.Add 5.0mLof Diluted Dithizone Extraction Solution,shake vigorously,and allow the layers to separate.Using Diluted Dithiazone Extraction Solutionas a color blank,compare the colors developed in the chloroform layers of the solution under test and the control solution:the color developed by the solution under test is not more intense than that developed by the control solution (3µg per g).
Organic volatile impurities,Method IVá467ñ:
meets the requirements.
Assay—
Transfer 500mg of Ferrous Fumarate,accurately weighed,to a 500-mLconical flask,and add 25mLof dilute hydrochloric acid (2in 5).Heat to boiling,and add a solution of 5.6g of stannous chloride in 50mLof dilute hydrochloric acid (3in 10)dropwise until the yellow color disappears,then add 2drops in excess.Cool the solution in an ice bath to room temperature,add 10mLof mercuric chloride solution (1in 20),and allow to stand for 5minutes.Add 200mLof water,25mLof dilute sulfuric acid (1in 2),and 4mLof phosphoric acid,then add 2drops of orthophenanthroline TS,and titrate with 0.1Nceric sulfate VS.Perform a blank determination,and make any necessary correction.Each mLof 0.1Nceric sulfate is equivalent to 16.99mg of C4H2FeO4.
Auxiliary Information—
Staff Liaison:Lawrence Evans,III,Ph.D.,Scientist
Expert Committee:(DSN)Dietary Supplements:Non-Botanicals
USP28–NF23Page 816
Pharmacopeial Forum:Volume No.29(3)Page 629
Phone Number:1-301-816-8389