Flecainide Acetate
;)
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 98.0percent and not more than 101.0percent 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 250mg of it in a test tube about 18mm in diameter,adding 10mLof water and 1drop 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—
A:
Infrared Absorption á197Kñ.
Solution:
130µg per mL.
Medium:
alcohol.
Absorptivities at 298nm,calculated on the dried basis,do not differ by more than 3.0%.
Melting range á741ñ:
between 146
and 152,but the range between beginning and end of melting does not exceed 3.
and 152,but the range between beginning and end of melting does not exceed 3.
Loss on drying á731ñ—
Dry it in a vacuum at a pressure not exceeding 5mm of mercury at 60for 2hours:it loses not more than 0.5%of its weight.
for 2hours:it loses not more than 0.5%of its weight.
Residue on ignition á281ñ:
not more than 0.2%.
Heavy metals,Method IIá231ñ:
not more than 0.002%.
Chromatographic purity—
Mobile phase—
Prepare a mixture of water,acetonitrile,glacial acetic acid,and 1.0Ntetrabutylammonium hydroxide in methanol (710:290:10:5).Adjust with ammonium hydroxide to a pHof 5.8±0.05.Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).
Diluent—
Prepare a mixture of water and acetonitrile (71:29).
Standard solution—
Prepare a solution of USP Flecainide Acetate RSand USP Flecainide Related Compound A RSin Diluenthaving known concentrations of about 0.1mg of each per mL.
Test solution—
Transfer about 250mg of Flecainide Acetate,accurately weighed,to a 25-mLvolumetric flask,dissolve in and dilute with Diluentto volume,and mix.
Chromatographic system
(see Chromatography á621ñ)—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 2mLper minute.Chromatograph the Standard preparation,and record the responses as directed for Procedure:the relative retention times are 1.0for flecainide and about 1.7for flecainide related compound A;the resolution,R,between flecainide and e flecainide related compound Ais 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 20µL)of the Standard solutionand the Test solutioninto the chromatograph,record the chromatograms,and measure the responses for all the peaks.Calculate the percentage of flecainide related compound Ain the portion of Flecainide Acetate taken by the formula:
2500(CA/WU)(rUA/rSA),
in which CAis the concentration,in mg per mL,of USP Flecainide Related Compound A RSin the Standard solution;WUis the weight,in mg,of Flecainide Acetate taken to prepare the Test solution;and rUAand rSAare the flecainide related compound Apeak responses obtained from the Test solutionand 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 CFis the concentration,in mg per mL,of USP Flecainide RSin the Standard solution;WUis the weight,in mg,of Flecainide Acetate taken to prepare the Test solution;riis the peak response for any individual impurity observed in the chromatogram obtained from the Test solution;and rFis 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 600mg of Flecainide Acetate,accurately weighed,in about 100mLof dimethylformamide,and stir by mechanical means until dissolved.Titrate with 0.1Ntetrabutylammonium hydroxide VS,determining the endpoint potentiometrically (see Titrimetry á541ñ).Perform a blank determination and make any necessary correction.Each mLof 0.1Ntetrabutylammonium hydroxide is equivalent to 6.005mg of C2H4O2:between 12.4%and 12.8%,calculated on the dried basis,is found.
Assay—
Dissolve about 600mg of Flecainide Acetate,accurately weighed,in about 20mLof glacial acetic acid,and stir by mechanical means until dissolved.Titrate with 0.1Nperchloric acid VS,determining the endpoint potentiometrically (see Titrimetry á541ñ).Perform a blank determination and make any necessary correction.Each mLof 0.1Nperchloric acid is equivalent to 47.44mg of C17H20F6N2O3·C2H4O2.
Auxiliary Information—
Staff Liaison:Andrzej Wilk,Ph.D.,Senior Scientific Associate
Expert Committee:(PA5)Pharmaceutical Analysis 5
USP28–NF23Page 826
Phone Number:1-301-816-8305