Dissolution 
711
—
Medium:
0.01 N hydrochloric acid; 900 mL.
Apparatus 2:
50 rpm.
Time:
30 minutes.
Procedure—
Determine the amounts of acetaminophen (C8H9NO2) 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.
Assay—
Buffer solution—
Dissolve 2.04 g of monobasic potassium phosphate in about 950 mL of water. Add 2 mL of triethylamine, adjust with phosphoric acid to a pH of 2.35, dilute with water to 1000 mL, and mix.
Mobile phase—
Prepare a filtered and degassed mixture of
Buffer solution and methanol (92:8). Make adjustments if necessary (see
System Suitability under
Chromatography 621).
Codeine phosphate standard stock solution—
Dissolve an accurately weighed quantity of
USP Codeine Phosphate RS in
Mobile phase to obtain a solution having a known concentration of about 0.3 mg per mL.
Standard preparation—
Transfer about 30 mg of
USP Acetaminophen RS and 100
J mL of
Codeine phosphate standard stock solution, J being the ratio of the labeled amount, in mg, of codeine phosphate hemihydrate to that of acetaminophen, to a 100-mL volumetric flask, dilute with
Mobile phase to volume, and mix. This solution contains about 0.3 mg of acetaminophen and 0.3
J mg of codeine phosphate hemihydrate per mL.
Assay preparation—
Weigh and finely powder not fewer than 20 Tablets. Transfer an accurately weighed portion of the powder, 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.
Chromatographic system (see Chromatography 621)—
The liquid chromatograph is equipped with a 214-nm detector and a 4.6-mm × 25-cm column that contains 5-µm packing L1. The flow rate is about 1.5 mL per minute. Chromatograph the
Standard preparation, and record the peak responses as directed for
Procedure: the resolution,
R, between acetaminophen and codeine phosphate is not less than 2.0; and the relative standard deviation for replicate injections is not more than 2.0% and 3.0%, respectively.
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 (C
8H
9NO
2) in the portion of Tablets taken by the formula:
(LCA / CU)(rU / rS),
in which
L is the labeled quantity, in mg, of acetaminophen in each Tablet;
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 Tablet 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 (C
18H
21NO
3·H
3PO
4·½H
2O) in the portion of Tablets taken by the formula:
(406.37/397.37)(LCC / CU)(rU / rS),
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 Tablet;
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 Tablet and the extent of dilution; and the other terms are as defined herein.
