Dissolution á711ñ—
Medium:
0.01Nhydrochloric acid;900mL.
Apparatus 2:
50rpm.
Time:
30minutes.
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 0.01Nhydrochloric acid to prepare the Codeine phosphate standard stock solutionand to make any other necessary volumetric adjustments.
Tolerances—
Not less than 75%(Q)of the labeled amounts of C8H9NO2and C18H21NO3·H3PO4·½H2Ois dissolved in 30minutes.
Assay—
Buffer solution—
Dissolve 2.04g of monobasic potassium phosphate in about 950mLof water.Add 2mLof triethylamine,adjust with phosphoric acid to a pHof 2.35,dilute with water to 1000mL,and mix.
Mobile phase—
Prepare a filtered and degassed mixture of
Buffer solutionand methanol (92:8).Make adjustments if necessary (see
System Suitabilityunder
Chromatography á621ñ).
Codeine phosphate standard stock solution—
Dissolve an accurately weighed quantity of
USP Codeine Phosphate RSin
Mobile phaseto obtain a solution having a known concentration of about 0.3mg per mL.
Standard preparation—
Transfer about 30mg of
USP Acetaminophen RSand 100
JmLof
Codeine phosphate standard stock solution,Jbeing the ratio of the labeled amount,in mg,of codeine phosphate hemihydrate to that of acetaminophen,to a 100-mLvolumetric flask,dilute with
Mobile phaseto volume,and mix.This solution contains about 0.3mg of acetaminophen and 0.3
Jmg of codeine phosphate hemihydrate per mL.
Assay preparation—
Weigh and finely powder not fewer than 20Tablets.Transfer an accurately weighed portion of the powder,equivalent to about 300mg of acetaminophen,to a 100-mLvolumetric flask,add about 75mLof Mobile phase,and sonicate for 10minutes.Dilute with Mobile phaseto volume,and mix.Transfer 5.0mLof the resulting solution to a 50-mLvolumetric flask,dilute with Mobile phaseto volume,and mix.Pass a portion of this solution through a suitable 1-µm filter.
Chromatographic system (see Chromatography á621ñ)—
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 1.5mLper 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 30µL)of the
Standard preparationand the
Assay preparationinto 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
Lis the labeled quantity,in mg,of acetaminophen in each Tablet;
CAis the concentration,in mg per mL,of
USP Acetaminophen RSin the
Standard preparation;CUis 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
rUand
rSare the peak responses obtained from the
Assay preparationand 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 406.37and 397.37are the molecular weights of codeine phosphate hemihydrate and anhydrous codeine phosphate,respectively;
Lis the labeled quantity,in mg,of codeine phosphate hemihydrate in each Tablet;
CCis the concentration,in mg per mL,of
USP Codeine Phosphate RSin the
Standard preparation;CUis 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.