Medium: water;900mL.

Apparatus 2: 75rpm.

Time: 45minutes.

Determination of dissolved aspirinand carisoprodol— Proceed as directed in the test for Dissolutionunder Carisoprodol and Aspirin Tablets.

Determination of dissolved codeine phosphate—

MOBILEPHASE —Dissolve 2.2g of docusate sodium and 0.8g of ammonium nitrate in 550mLof water,and filter through a membrane filter of 0.5µm or finer porosity.Add 450mLof similarly filtered acetonitrile to the filtrate,mix,and degas.

STANDARDPREPARATION —Dissolve an accurately weighed quantity of USP Codeine Phosphate RSin water to obtain a solution having a known concentration of about 18µg per mL.

CHROMATOGRAPHICSYSTEM (see Chromatography á621ñ)—The liquid chromatograph is equipped with a 254-nm detector and a 3.9-mm ×30-cm column that contains packing L1.The flow rate is about 2mLper minute.Chromatograph the Standard preparation,and record the peak responses as directed for Procedure:the relative standard deviation for replicate injections is not more than 2.0%.

PROCEDURE —Separately inject equal volumes (about 50µL)of the Standard preparationand the solution under test,previously filtered,into the chromatograph,record the chromatograms,and measure the responses for the major peaks.Calculate the quantity,in mg,of codeine phosphate (C18H21NO3·H3PO4·½H2O)dissolved by the formula: in which 406.37and 397.37are the molecular weights of codeine phosphate hemihydrate and anhydrous codeine phosphate,respectively,Cis the concentration,in µg per mL,of USP Codeine Phosphate RSin the Standard preparation,and rUand rSare the peak responses for the codeine phosphate peaks from the solution under test and the Standard preparation,respectively.

Tolerances— Not less than 75%(Q)of the labeled amounts of C9H8O4,C12H24N2O4,and C18H21NO3·H3PO4·½H2Oare dissolved in 45minutes.

Mobile phase ,Solvent mixture,Aspirin and carisoprodol standard preparation,Salicylic acid standard preparation,and Resolution solution—Prepare as directed in the Assay for aspirin and carisoprodol and limit of free salicylic acidunder Carisoprodol and Aspirin Tablets.

Assay preparation— Weigh and finely powder not less than 20Tablets.Transfer an accurately weighed portion of the powder,equivalent to about 325mg of aspirin,to a 100-mLvolumetric flask.Add about 50mLof Solvent mixture,swirl for 5minutes,sonicate for 25to 30seconds,shake by mechanical means for 30minutes,dilute with Solvent mixtureto volume,and mix.Filter a portion of this solution through a membrane filter of 0.5µm or finer porosity,and use the filtrate as the Assay preparation.

Chromatographic system and Procedure—Proceed as directed in the Assay for aspirin and carisoprodol and limit of free salicylic acidunder Carisoprodol and Aspirin Tablets.

Mobile phase— Dissolve 2.2g of docusate sodium in 600mLof methanol.Dissolve 0.8g of ammonium nitrate in 400mLof water.Mix these two solutions,adjust with glacial acetic acid to a pHof 3.3±0.05,filter through a membrane filter of 0.5µm or finer porosity,and degas.Make adjustments if necessary (see System Suitabilityunder Chromatography á621ñ).

Solvent mixture— Mix equal volumes of methanol and 0.01Nsulfuric acid.

Standard preparation— Dissolve accurately weighed quantities of USP Codeine Phosphate RSand USP Aspirin RSin Solvent mixture,with the aid of swirling for 5minutes and sonication for 25to 30seconds,to obtain a solution having known concentrations of about 0.16mg of codeine phosphate and 0.16Jmg of aspirin per mL,Jbeing the ratio of the labeled amount,in mg,of aspirin to that of codeine phosphate.

Resolution solution— Transfer about 8mg of USP Codeine Phosphate RSto a 50-mLvolumetric flask containing about 6mg of USP Codeine N-Oxide RS,dilute with Solvent mixtureto volume,and mix.

Assay preparation— Weigh and finely powder not less than 20Tablets.Transfer an accurately weighed portion of the powder,equivalent to about 16mg of codeine phosphate,to a 100-mLvolumetric flask.Add about 50mLof Solvent mixture,sonicate for 30minutes,shake by mechanical means for about 30minutes,dilute with Solvent mixtureto volume,and mix.

Chromatographic system (see Chromatography á621ñ)—The liquid chromatograph is equipped with a 254-nm detector and a 3.9-mm ×30-cm column that contains packing L1.The flow rate is about 1.5mLper minute.Chromatograph the Resolution solutionand the Standard preparation,and record the peak responses as directed for Procedure:the resolution,R,between the codeine phosphate and codeine N-Oxide peaks is not less than 1.2,and the relative standard deviation for replicate injections of the Standard preparationis not more than 2.0%.

Procedure— Separately inject equal volumes (about 50µL)of the Standard preparationand the Assay preparationinto the chromatograph,record the chromatograms,and measure the responses for the major peaks.The relative retention times are about 0.9for codeine N-Oxide and 1.0for codeine phosphate.Calculate the quantity,in mg,of codeine phosphate (C18H21NO3·H3PO4·½H2O)in the portion of Tablets taken by the formula: in which 406.37and 397.37are the molecular weights of codeine phosphate hemihydrate and anhydrous codeine phosphate,respectively,Cis the concentration,in mg per mL,of USP Codeine Phosphate RSin the Standard preparation,and rUand rSare the peak responses for the codeine phosphate peak obtained from the Assay preparationand the Standard preparation,respectively.