Disopyramide Phosphate Capsules
»Disopyramide Phosphate Capsules contain an amount of Disopyramide Phosphate equivalent to not less than 90.0percent and not more than 110.0percent of the labeled amount of disopyramide (C21H29N3O).
Packaging and storage— Preserve in well-closed containers.
Identification— Transfer a portion of Capsule contents,equivalent to about 125mg of disopyramide phosphate,to a 25-mLvolumetric flask,add 20mLof methanol,and shake by mechanical means for 20minutes.Dilute with methanol to volume,mix,and filter through paper (Whatman No.2or equivalent),discarding the first 10mLof the filtrate.Apply 10µLeach of the subsequent filtrate and of a solution of USP Disopyramide Phosphate RSin methanol containing 6.2mg per mLto a suitable 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 a solvent system consisting of a mixture of toluene,alcohol,and ammonium hydroxide (170:28:2)until the solvent front has moved about three-fourths of the length of the plate.Remove the plate from the developing chamber,mark the solvent front,and allow the solvent to evaporate.Locate the spots on the plate by viewing under short-wavelength UVlight:the RFvalue of the principal spot obtained from the test solution corresponds to that obtained from the Standard solution.
Dissolution á711ñ—
Medium: water;1000mL.
Apparatus 2: 50rpm.
Time: 20minutes.
Procedure— Filter 15mLof the solution under test,and transfer 10.0mLof the filtrate to a 25-mLvolumetric flask.Dilute with 2Nsulfuric acid to volume,and mix.Determine the amount of disopyramide (C21H29N3O)dissolved from UVabsorbances at the wavelength of maximum absorbance at about 268nm of this solution,using water as the blank,in comparison with a Standard solution having a known concentration of USP Disopyramide Phosphate RSin the same medium.
Tolerances— Not less than 80%(Q)of the labeled amount of C21H29N3Ois dissolved in 20minutes.
Uniformity of dosage units á905ñ: meet the requirements.
Assay—
Methanolic sulfuric acid— Cautiously add 5.4mLof sulfuric acid to about 1800mLof methanol with stirring,dilute with methanol to 2000mL,and mix.
Procedure— Weigh the contents of not fewer than 20Phosphate Capsules,and calculate the average weight per Capsule.Mix the combined contents of the Capsules,and transfer an accurately weighed portion,equivalent to about 125mg of disopyramide phosphate,to a glass-stoppered,125-mLflask.Add 50mLof Methanolic sulfuric acid,and stir for 30minutes.Filter through a medium-porosity,sintered-glass filter,and rinse thoroughly with Methanolic sulfuric acid.Transfer the combined filtrate and rinsings to a 100-mLvolumetric flask,dilute with Methanolic sulfuric acidto volume,and mix.Dilute an accurately measured portion of this solution quantitatively and stepwise with the same solvent to obtain a solution having a concentration of about 40µg per mL.Dissolve an accurately weighed portion of USP Disopyramide Phosphate RSin Methanolic sulfuric acid,and dilute quantitatively and stepwise with the same solvent to obtain a solution having a known concentration of about 40µg per mL.Concomitantly determine the absorbances of both solutions in 1-cm cells at the wavelength of maximum absorbance at about 268nm,with a suitable spectrophotometer,using Methanolic sulfuric acidas the blank.Calculate the quantity,in mg,of C21H29N3Oin the portion of Capsules taken by the formula:
3.125(339.48/437.47)C(AU/AS),
in which 339.48and 437.47are the molecular weights of disopyramide and disopyramide phosphate,respectively;Cis the concentration,in µg per mL,of USP Disopyramide Phosphate RSin the Standard solution;and AUand ASare the absorbances of the solution from the Capsules and the Standard solution,respectively.
Auxiliary Information— Staff Liaison:Andrzej Wilk,Ph.D.,Senior Scientific Associate
Expert Committee:(PA5)Pharmaceutical Analysis 5
USP28–NF23Page 677
Phone Number:1-301-816-8305