Fumaric Acid
116.072-Butenedioic acid, E-.
Fumaric acid
[110-17-8].» Fumaric Acid contains not less than 99.5 percent and not more than 100.5 percent of C4H4O4, calculated on the anhydrous basis.
Packaging and storage—
Preserve in well-closed containers.
Identification—
Dissolve about 10 mg in 25 mL of water, and to this solution add 1 mL of a solution prepared by mixing 20 mL of copper sulfate solution (1 in 5) and 8 mL of pyridine: a precipitate is formed in the blue solution within 1 minute.
Water, Method I 
921
:
0.5%.
921:
0.5%.
Residue on ignition 281:
not more than 0.1%.
281:
not more than 0.1%.
Heavy metals, Method II 231:
0.001%.
231:
0.001%.
Limit of maleic acid—
Mobile phase—
Prepare 0.005 N sulfuric acid that has been suitably filtered and degassed.
Standard preparation—
Using Mobile phase as the solvent, prepare a solution containing an accurately known concentration of about 0.001 mg of USP Maleic Acid RS per mL.
Test preparation—
Transfer about 100 mg of Fumaric Acid, accurately weighed, to a 100-mL volumetric flask, dissolve in Mobile phase, dilute with Mobile phase to volume, and mix.
Resolution solution—
Using Mobile phase as the solvent, prepare a solution containing about 10 µg of USP Fumaric Acid RS per mL, and about 5 µg of USP Maleic Acid RS per mL.
Chromatographic system
(see Chromatography 621)—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 0.3 mL per 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%.
621)—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 0.3 mL per 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 5 µL) of the Standard preparation and the Test preparation into the chromatograph, record the chromatograms, and measure the peak responses. The relative retention times are about 0.5 for maleic acid and 1.0 for 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 C is the concentration, in mg per mL, of USP Maleic Acid RS in the Standard preparation, and rU and rS are the responses of the maleic acid peaks obtained from the Test preparation and the Standard preparation, respectively. Not more than 0.1% of maleic acid is found.
Assay—
Transfer about 1 g of Fumaric Acid, accurately weighed, to a conical flask, add 50 mL of methanol, and warm gently on a steam bath to effect solution. Cool, add phenolphthalein TS, and titrate with 0.5 N sodium hydroxide VS to the first appearance of a pink color that persists for not less than 30 seconds. Perform a blank titration, and make any necessary correction. Each mL of 0.5 N sodium hydroxide is equivalent to 29.02 mg of C4H4O4.
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
Chromatographic Column—
| Topic/Question | Contact | Expert Committee |
| Monograph | Robert H. Lafaver, B.A.
Scientist 1-301-816-8335 |
(EM105) Excipient Monographs 1 |
| Reference Standards | Lili Wang, Technical Services Scientist 1-301-816-8129 RSTech@usp.org |
USP32–NF27 Page 1238
Chromatographic columns text is not derived from, and not part of, USP 32 or NF 27.