(bis'' oh proe' lol fue' ma rate).
» Bisoprolol Fumarate contains not less than 97.5 percent and not more than 102.0 percent of (C18H31NO4)2·C4H4O4, calculated on the anhydrous basis.
Packaging and storage Preserve in tight, light-resistant containers. Store at controlled room temperature.
USP Reference standards 11
B: The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.
Specific rotation 781: between 2 and +2.
Test solution: 10 mg per mL, in methanol.
Water, Method I 921: not more than 0.5%.
Residue on ignition 281: not more than 0.1%.
Heavy metals, Method I 231: 0.002%.
Diluent, Mobile phase, System suitability solution, and Chromatographic system Proceed as directed in the Assay.
Standard solution Prepare as directed for Standard preparation in the Assay.
Test solution Prepare as directed for Assay preparation in the Assay.
Procedure Inject a volume (about 10 µL) of the Test solution into the chromatograph, record the chromatogram, and measure the peak areas. Calculate the percentage of total impurities in the portion of Bisoprolol Fumarate taken by the formula:
100(ri / rs)in which ri is the sum of areas for all the peaks, excluding the fumaric acid and bisoprolol peaks; and rs is the sum of the areas of all the peaks in the chromatogram: not more than 0.5% of total impurities is found.
Content of fumaric acid Transfer about 500 mg of Bisoprolol Fumarate, accurately weighed, to a beaker, and dissolve in 70 mL of dehydrated alcohol. Add 8.0 mL of 0.1 N tetrabutylammonium hydroxide VS, and stir for 2 minutes. Titrate with 0.1 N tetrabutylammonium hydroxide VS, determining the endpoint potentiometrically, using a glass-calomel electrode system. Perform a blank determination, and make any necessary correction (see Titrimetry 541). Each mL of 0.1 N tetrabutylammonium hydroxide is equivalent to 5.804 mg of fumaric acid: not less than 14.8% and not more than 15.4% of fumaric acid is found, calculated on the anhydrous basis.
Diluent Prepare a mixture of water and acetonitrile (65:35).
Mobile phase To a 1-L portion of Diluent add 5 mL of heptafluorobutyric acid, 5 mL of diethylamine, and 2.5 mL of formic acid. Mix, filter, and degas. Make adjustments if necessary (see System Suitability under Chromatography 621).
System suitability solution Prepare a solution in Diluent containing about 0.5 mg of propranolol hydrochloride and 1 mg of Bisoprolol Fumarate per mL.
Standard preparation Quantitatively dissolve an accurately weighed quantity of USP Bisoprolol Fumarate RS in Diluent to obtain a solution having a known concentration of about 1 mg per mL.
Assay preparation Transfer about 50 mg of Bisoprolol Fumarate, accurately weighed, to a 50-mL volumetric flask. Dissolve in and dilute with Diluent to volume, and mix.
Chromatographic system (see Chromatography 621) The liquid chromatograph is equipped with a 273-nm detector and a 4.6-mm × 12.5-cm column that contains packing L7. The flow rate is about 1 mL per minute. Chromatograph the System suitability solution, and record the peak areas as directed for Procedure: the resolution, R, between bisoprolol and propranolol is not less than 7.0. Chromatograph the Standard preparation, and record the peak areas as directed for Procedure: the tailing factor is not more than 2.0; and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure Separately inject equal volumes (about 10 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the areas for the major peaks. Calculate the quantity, in mg, of (C18H31NO4)2·C4H4O4 in the portion of Bisoprolol Fumarate taken by the formula:
50C(rU / rS)in which C is the concentration, in mg per mL, of USP Bisoprolol Fumarate RS in the Standard preparation; and rU and rS are the peak areas obtained from the Assay preparation and the Standard preparation, respectively.
Auxiliary Information Please check for your question in the FAQs before contacting USP.
USP35NF30 Page 2373Pharmacopeial Forum: Volume No. 29(3) Page 609