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Flecainide Acetate
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C17H20F6N2O3·C2H4O2 474.39

Benzamide, N-(2-piperidinylmethyl)-2,5-bis(2,2,2-trifluoroethoxy)-, monoacetate.
N-(2-Piperidylmethyl)-2,5-bis(2,2,2-trifluoroethoxy)benzamide monoacetate [54143-56-5].
» Flecainide Acetate contains not less than 98.0 percent and not more than 101.0 percent of C17H20F6N2O3·C2H4O2, calculated on the dried basis.
Packaging and storage— Preserve in well-closed containers.
Clarity of solution— Prepare a test solution by placing 250 mg of it in a test tube about 18 mm in diameter, adding 10 mL of water and 1 drop of glacial acetic acid, and shaking to dissolve it. The solution is colorless and is not less clear than an equal volume of water in a similar test tube.
Identification—
Solution: 130 µg per mL.
Medium: alcohol.
Absorptivities at 298 nm, calculated on the dried basis, do not differ by more than 3.0%.
Melting range 741: between 146 and 152, but the range between beginning and end of melting does not exceed 3.
Loss on drying 731— Dry it in a vacuum at a pressure not exceeding 5 mm of mercury at 60 for 2 hours: it loses not more than 0.5% of its weight.
Residue on ignition 281: not more than 0.2%.
Heavy metals, Method II 231: not more than 0.002%.
Chromatographic purity—
Mobile phase— Prepare a mixture of water, acetonitrile, glacial acetic acid, and 1.0 N tetrabutylammonium hydroxide in methanol (710:290:10:5). Adjust with ammonium hydroxide to a pH of 5.8 ± 0.05. Make adjustments if necessary (see System Suitability under Chromatography 621).
Diluent— Prepare a mixture of water and acetonitrile (71:29).
Standard solution— Prepare a solution of USP Flecainide Acetate RS and USP Flecainide Related Compound A RS in Diluent having known concentrations of about 0.1 mg of each per mL.
Test solution— Transfer about 250 mg of Flecainide Acetate, accurately weighed, to a 25-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 254-nm detector and a 4.6-mm × 15-cm column containing 5-µm packing L7. The flow rate is about 2 mL per minute. Chromatograph the Standard preparation, and record the responses as directed for Procedure: the relative retention times are 1.0 for flecainide and about 1.7 for flecainide related compound A; the resolution, R, between flecainide and e flecainide related compound A is not less than 2; and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure— [NOTE—Use peak areas where peak responses are indicated.] Separately inject equal volumes (about 20 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the responses for all the peaks. Calculate the percentage of flecainide related compound A in the portion of Flecainide Acetate taken by the formula:
2500(CA / WU)(rUA / rSA),
in which CA is the concentration, in mg per mL, of USP Flecainide Related Compound A RS in the Standard solution; WU is the weight, in mg, of Flecainide Acetate taken to prepare the Test solution; and rUA and rSA are the flecainide related compound A peak responses obtained from the Test solution and the Standard solution, respectively. Not more than 0.5% is found. Calculate the percentage of any other impurity in the portion of Flecainide Acetate taken by the formula:
2500(CF / WU)(ri / rF),
in which CF is the concentration, in mg per mL, of USP Flecainide RS in the Standard solution;WU is the weight, in mg, of Flecainide Acetate taken to prepare the Test solution; ri is the peak response for any individual impurity observed in the chromatogram obtained from the Test solution; and rF is the flecainide peak response obtained from the Standard solution. Not more than 0.5% is found, and the sum of all impurities found is not greater than 2.0%.
Content of acetate— Dissolve about 600 mg of Flecainide Acetate, accurately weighed, in about 100 mL of dimethylformamide, and stir by mechanical means until dissolved. Titrate with 0.1 N tetrabutylammonium hydroxide VS, determining the endpoint potentiometrically (see Titrimetry 541). Perform a blank determination and make any necessary correction. Each mL of 0.1 N tetrabutylammonium hydroxide is equivalent to 6.005 mg of C2H4O2: between 12.4% and 12.8%, calculated on the dried basis, is found.
Residual solvents 467: meets the requirements.
(Official January 1, 2007)
Assay— Dissolve about 600 mg of Flecainide Acetate, accurately weighed, in about 20 mL of glacial acetic acid, and stir by mechanical means until dissolved. Titrate with 0.1 N perchloric acid VS, determining the endpoint potentiometrically (see Titrimetry 541). Perform a blank determination and make any necessary correction. Each mL of 0.1 N perchloric acid is equivalent to 47.44 mg of C17H20F6N2O3·C2H4O2.
Auxiliary Information— Staff Liaison : Andrzej Wilk, Ph.D., Senior Scientific Associate
Expert Committee : (MDCV05) Monograph Development-Cardiovascular
USP29–NF24 Page 909
Phone Number : 1-301-816-8305