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 99.0percent and not more than 100.5percent of (C15H25NO3)2·C4H4O4,calculated on the dried basis.
Packaging and storage—
Preserve in tight,light-resistant containers.
Identification—
A:
Infrared Absorption á197Kñ.
B:
Prepare a test solution in methanol containing 10mg per mL.Separately apply 20µLof the test solution and 20µLof a Standard solution of USP Metoprolol Fumarate RScontaining 10mg per mLto a thin-layer chromatographic plate (see Chromatography á621ñ)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 30minutes,and spray the plate with bromocresol purple TS.Examine the chromatograms:the RFvalue of the yellow spot obtained from the test solution corresponds to that obtained from the Standard solution.
for 30minutes,and spray the plate with bromocresol purple TS.Examine the chromatograms:the RFvalue of the yellow spot obtained from the test solution corresponds to that obtained from the Standard solution.
pHá791ñ:
between 5.5and 6.5,in a solution (1in 10).
Loss on drying á731ñ—
Dry it in vacuum at 60for 4hours:it loses not more than 0.5%of its weight.
for 4hours:it loses not more than 0.5%of its weight.
Residue on ignition á281ñ:
not more than 0.1%.
Heavy metals,Method Iá231ñ:
0.001%.
Organic volatile impurities,Method Iá467ñ:
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 Diluentto obtain solutions having known concentrations of 1.0,0.5,0.2,and 0.1mg per mL,respectively.
Test solution—
Dissolve a quantity of Metoprolol Fumarate in Diluentto obtain a solution containing 100mg per mL.
Chromatographic chamber
and Detecting reagent—Prepare as directed in the test for Chromatographic purityunder Metoprolol Tartrate.
Procedure—
Proceed as directed for Procedurein the test for Chromatographic purityunder Metoprolol Tartrate:the specified results are obtained.
Assay—
Dissolve about 325mg of Metoprolol Fumarate,accurately weighed,in 20mLof glacial acetic acid,and titrate with 0.1Nperchloric acid VS,determining the endpoint potentiometrically,using a glass electrode and a calomel electrode containing glacial acetic acid saturated with lithium chloride (see Titrimetry á541ñ).Perform a blank determination,and make any necessary correction.Each mLof 0.1Nperchloric acid is equivalent to 32.54mg of (C15H25NO3)2·C4H4O4.
Auxiliary Information—
Staff Liaison:Andrzej Wilk,Ph.D.,Senior Scientific Associate
Expert Committee:(PA5)Pharmaceutical Analysis 5
USP28–NF23Page 1278
Phone Number:1-301-816-8305