A: The retention times of the major peaks in the chromatogram of the Assay preparation correspond to those in the chromatogram of the Standard preparation, as obtained in the Assay.

B: Transfer a portion of Capsule contents, equivalent to about 12 mg of codeine phosphate, to a separator, add 5 mL of water, 1 mL of ammonium hydroxide, and 5 mL of methylene chloride, shake for 1 minute, and allow the layers to separate. Use the clear, lower layer as the test solution. Prepare a Standard solution of USP Acetaminophen RS and USP Codeine Phosphate RS in methanol containing 12 mg of each per mL. Apply 10 µL of each solution to a suitable thin-layer chromatographic plate (see Chromatography 621) 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 methanol and ammonium hydroxide (49:1) 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 examination under short-wavelength UV light: the RF values of the two principal spots obtained from the test solution correspond to those obtained from the Standard solution.

Medium: 0.01 N hydrochloric acid; 900 mL.

Apparatus 2: 50 rpm.

Time: 30 minutes.

Procedure— Determine the amounts of acetaminophen (C8H9 NO2) and codeine phosphate hemihydrate (C18H21NO3·H3PO4 · ½H2O) dissolved by employing the procedure set forth in the Assay, except to use 0.01 N hydrochloric acid to prepare the Codeine phosphate standard stock solution and to make any other necessary volumetric adjustments.

Tolerances— Not less than 75% (Q) of the labeled amounts of C8H9NO2 and C18H21NO3·H3PO4 · ½H2O is dissolved in 30 minutes.

PROCEDURE FOR CONTENT UNIFORMITY—

(Official January 1, 2007)

Buffer solution, Mobile phase, Codeine phosphate standard stock solution, Standard preparation, and Chromatographic system— Prepare as directed in the Assay under Acetaminophen and Codeine Phosphate Tablets.

Assay preparation— Remove as completely as possible the contents of not fewer than 20 Capsules, weigh, and mix. Transfer an accurately weighed portion of the combined contents, equivalent to about 300 mg of acetaminophen, to a 100-mL volumetric flask, add about 75 mL of Mobile phase, and sonicate for 10 minutes. Dilute with Mobile phase to volume, and mix. Transfer 5.0-mL of the resulting solution to a 50-mL volumetric flask, dilute with Mobile phase to volume, and mix. Pass a portion of this solution through a suitable 1-µm filter.

Procedure— Separately inject equal volumes (about 30 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the peak responses. Calculate the quantity, in mg, of acetaminophen (C8H9NO2) in the portion of Capsules taken by the formula: in which L is the labeled quantity, in mg, of acetaminophen in each Capsule; CA is the concentration, in mg per mL, of USP Acetaminophen RS in the Standard preparation; CU is the concentration, in mg per mL, of acetaminophen in the Assay preparation, based upon the labeled quantity per Capsule and the extent of dilution; and rU and rS are the peak responses obtained from the Assay preparation and the Standard preparation, respectively. Calculate the quantity, in mg, of codeine phosphate hemihydrate (C18H21NO3·H3PO4 · ½H2O) in the portion of Capsules taken by the formula: in which 406.37 and 397.37 are the molecular weights of codeine phosphate hemihydrate and anhydrous codeine phosphate, respectively; L is the labeled quantity, in mg, of codeine phosphate hemihydrate in each Capsule; CC is the concentration, in mg per mL, of USP Codeine Phosphate RS in the Standard preparation; CU is the concentration, in mg per mL, of codeine phosphate hemihydrate in the Assay preparation, based upon the labeled quantity per Capsule and the extent of dilution; and the other terms are as defined herein.