»Fumaric Acid contains not less than 99.5percent and not more than 100.5percent of C4H4O4,calculated on the anhydrous basis.
Packaging and storage Preserve in well-closed containers.
Identification Dissolve about 10mg in 25mLof water,and to this solution add 1mLof a solution prepared by mixing 20mLof copper sulfate solution (1in 5)and 8mLof pyridine:a precipitate is formed in the blue solution within 1minute.
Water,Method Iá921ñ: 0.5%.
Residue on ignition á281ñ: not more than 0.1%.
Heavy metals,Method IIá231ñ: 0.001%.
Limit of maleic acid
Mobile phase Prepare 0.005Nsulfuric acid that has been suitably filtered and degassed.
Standard preparation Using Mobile phaseas the solvent,prepare a solution containing an accurately known concentration of about 0.001mg of USP Maleic Acid RSper mL.
Test preparation Transfer about 100mg of Fumaric Acid,accurately weighed,to a 100-mLvolumetric flask,dissolve in Mobile phase,dilute with Mobile phaseto volume,and mix.
Resolution solution Using Mobile phaseas the solvent,prepare a solution containing about 10µg of USP Fumaric Acid RSper mL,and about 5µg of USP Maleic Acid RSper mL.
Chromatographic system (see Chromatography á621ñ)The liquid chromatograph is equipped with a 210-nm detector and a 4.6-mm ×22-cm column that contains packing L17.The flow rate is about 0.3mLper minute.Chromatograph the Resolution solution,and record the peak responses:the resolution,R,of the maleic acid and fumaric acid peaks is not less than 2.5,and the relative standard deviation of the maleic acid peak for replicate injections is not more than 2.0%.
Procedure Separately inject equal volumes (about 5µL)of the Standard preparationand the Test preparationinto the chromatograph,record the chromatograms,and measure the peak responses.The relative retention times are about 0.5for maleic acid and 1.0for fumaric acid.Calculate the quantity,in mg,of maleic acid in the total weight of Fumaric Acid taken by the formula:
100C(rU/rS),in which Cis the concentration,in mg per mL,of USP Maleic Acid RSin the Standard preparation,and rUand rSare the responses of the maleic acid peaks obtained from the Test preparationand the Standard preparation,respectively.Not more than 0.1%of maleic acid is found.
Organic volatile impurities,Method IVá467ñ: meets the requirements.
Solvent :dimethyl sulfoxide.
Assay Transfer about 1g of Fumaric Acid,accurately weighed,to a conical flask,add 50mLof methanol,and warm gently on a steam bath to effect solution.Cool,add phenolphthalein TS,and titrate with 0.5Nsodium hydroxide VSto the first appearance of a pink color that persists for not less than 30seconds.Perform a blank titration,and make any necessary correction.Each mLof 0.5Nsodium hydroxide is equivalent to 29.02mg of C4H4O4.
Auxiliary Information Staff Liaison:Catherine Sheehan,B.Sc.,Scientist
Expert Committee:(EMC)Excipients:Monograph Content