Medium: water; 900 mL.

Apparatus 2: 75 rpm.

Time: 45 minutes.

Determination of dissolved aspirin and carisoprodol— Proceed as directed in the test for Dissolution under Carisoprodol and Aspirin Tablets.

Determination of dissolved codeine phosphate—

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

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

CHROMATOGRAPHIC SYSTEM (see Chromatography 621)—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 2 mL per 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 50 µL) of the Standard preparation and 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 406.37 and 397.37 are the molecular weights of codeine phosphate hemihydrate and anhydrous codeine phosphate, respectively; C is the concentration, in µg per mL, of USP Codeine Phosphate RS in the Standard preparation; and rU and rS are 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·H3PO4·½H2O are dissolved in 45 minutes.

(Official January 1, 2007)

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 acid under Carisoprodol and Aspirin Tablets.

Assay preparation— Weigh and finely powder not fewer than 20 Tablets. Transfer an accurately weighed portion of the powder, equivalent to about 325 mg of aspirin, to a 100-mL volumetric flask. Add about 50 mL of Solvent mixture, swirl for 5 minutes, sonicate for 25 to 30 seconds, shake by mechanical means for 30 minutes, dilute with Solvent mixture to volume, and mix. Pass a portion of this solution through a membrane filter of 0.5 µm 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 acid under Carisoprodol and Aspirin Tablets.

Mobile phase— Dissolve 2.2 g of docusate sodium in 600 mL of methanol. Dissolve 0.8 g of ammonium nitrate in 400 mL of water. Mix these two solutions, adjust with glacial acetic acid to a pH of 3.3 ± 0.05, filter through a membrane filter of 0.5 µm or finer porosity, and degas. Make adjustments if necessary (see System Suitability under Chromatography 621).

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

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

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

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

Chromatographic system (see Chromatography 621)—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 1.5 mL per minute. Chromatograph the Resolution solution and 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 preparation is not more than 2.0%.

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