U.S. PHARMACOPEIA

Search USP29  
Metoprolol Fumarate
(C15H25NO3)2·C4H4O4 650.80

2-Propanol, 1-[4-(2-methoxyethyl)phenoxy]-3-[(1-methylethyl)amino]-, (±)-, (E)-2-butanedioate (2:1) (salt).
(±)-1-(Isopropylamino)-3-[p-(2-methoxyethyl)-phenoxy]-2-propanol fumarate (2:1) (salt) [119637-66-0].
» Metoprolol Fumarate contains not less than 99.0 percent and not more than 100.5 percent of (C15H25NO3)2·C4H4O4, calculated on the dried basis.
Packaging and storage— Preserve in tight, light-resistant containers.
Identification—
B: Prepare a test solution in methanol containing 10 mg per mL. Separately apply 20 µL of the test solution and 20 µL of a Standard solution of USP Metoprolol Fumarate RS containing 10 mg per mL to a thin-layer chromatographic plate (see Chromatography 621) coated with a 0.25-mm layer of chromatographic silica gel mixture. Allow the spots to dry, and develop the chromatogram in an unsaturated chamber with a solvent system consisting of a mixture of alcohol, water, and ammonium hydroxide (8:1:1) until the solvent front has moved about three-fourths of the length of the plate. Remove the plate from the chamber, mark the solvent front, dry at 110 for 30 minutes, and spray the plate with bromocresol purple TS. Examine the chromatograms: the RF value of the yellow spot obtained from the test solution corresponds to that obtained from the Standard solution.
Melting range 741: between 145 and 148.
pH 791: between 5.5 and 6.5, in a solution (1 in 10).
Loss on drying 731— Dry it in vacuum at 60 for 4 hours: it loses not more than 0.5% of its weight.
Residue on ignition 281: not more than 0.1%.
Organic volatile impurities, Method I 467: meets the requirements.
Chromatographic purity—
Diluent— Prepare a mixture of methanol and water (10:1).
Standard dilutions— Dissolve a suitable quantity of USP Metoprolol Fumarate RS, accurately weighed, in Diluent, and dilute quantitatively with Diluent to obtain solutions having known concentrations of 1.0, 0.5, 0.2, and 0.1 mg per mL, respectively.
Test solution— Dissolve a quantity of Metoprolol Fumarate in Diluent to obtain a solution containing 100 mg per mL.
Chromatographic chamber and Detecting reagent—Prepare as directed in the test for Chromatographic purity under Metoprolol Tartrate.
Procedure— Proceed as directed for Procedure in the test for Chromatographic purity under Metoprolol Tartrate: the specified results are obtained.
Residual solvents 467: meets the requirements.
(Official January 1, 2007)
Assay— Dissolve about 325 mg of Metoprolol Fumarate, accurately weighed, in 20 mL of glacial acetic acid, and titrate with 0.1 N perchloric acid VS, determining the endpoint potentiometrically, using a glass electrode and a calomel electrode containing glacial acetic acid saturated with lithium chloride (see Titrimetry 541). Perform a blank determination, and make any necessary correction. Each mL of 0.1 N perchloric acid is equivalent to 32.54 mg of (C15H25NO3)2·C4H4O4.
Auxiliary Information— Staff Liaison : Andrzej Wilk, Ph.D., Senior Scientific Associate
Expert Committee : (MDCV05) Monograph Development-Cardiovascular
USP29–NF24 Page 1417
Phone Number : 1-301-816-8305