Medium: water; 900 mL.

Apparatus 2: 75 rpm.

Time: 45 minutes.

Mobile phase— Mix 510 mL of methanol, previously filtered through a membrane filter of 0.5 µm or finer porosity, and 490 mL of glacial acetic acid solution (1 in 50), similarly filtered, and degas.

Standard preparation— Transfer about 90 mg of USP Aspirin RS and 90J mg of USP Carisoprodol RS, both accurately weighed, to a 250-mL volumetric flask, J being the ratio of the labeled amount, in mg, of carisoprodol to that of aspirin. Add 5 mL of acetonitrile, previously filtered through a membrane filter of 0.5 µm or finer porosity, swirl to dissolve, dilute with water to volume, and mix.

Resolution solution— Dissolve salicylic acid in Standard preparation to obtain a solution containing about 0.36 mg of salicylic acid per mL.

Chromatographic system (see Chromatography 621)—The liquid chromatograph is equipped with a refractive index detector and a 3.9-mm × 30-cm column that contains packing L1. Maintain the detector and the column at 30 ± 1. The flow rate is about 2 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 aspirin and salicylic acid peaks, and between the carisoprodol and salicylic acid peaks, is not less than 1.5; and the relative standard deviation for replicate injections of the Standard preparation is not more than 2.0%.

Procedure— Separately inject equal volumes (about 300 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. The relative retention times are about 0.4 for aspirin and 1.0 for carisoprodol. Calculate the quantity, in mg, of aspirin (C9H8O4) dissolved by the formula: in which C is the concentration, in µg per mL, of USP Aspirin RS in the Standard preparation; and rU and rS are the peak responses obtained for aspirin from the solution under test and the Standard preparation, respectively. Calculate the quantity, in mg, of carisoprodol (C12H24N2O4) dissolved by the same formula, except to read “USP Carisoprodol RS” where “USP Aspirin RS” is specified, and “carisoprodol” where “aspirin” is specified.

Tolerances— Not less than 75% (Q) of the labeled amounts of C9H8O4 and C12H24N2O4 are dissolved in 45 minutes.

(Official January 1, 2007)

Mobile phase— Mix 5 mL of glacial acetic acid and 500 mL of water, and pass through a membrane filter of 0.5 µm or finer porosity. Add 360 mL of the filtrate to 640 mL of methanol, similarly filtered, mix, and degas. Make adjustments if necessary (see System Suitability under Chromatography 621).

Solvent mixture— Prepare a mixture of water, acetonitrile, and glacial acetic acid (59:40:1).

Aspirin and carisoprodol standard preparation— Transfer about 80 mg of USP Aspirin RS and 80J mg of USP Carisoprodol RS, both accurately weighed, to a 25-mL volumetric flask, J being the ratio of the labeled amount, in mg, of carisoprodol to that of aspirin. Add about 15 mL of Solvent mixture, swirl for 5 minutes, and sonicate for 25 to 30 seconds. Dilute with Solvent mixture to volume, and mix.

Salicylic acid standard preparation— Dissolve an accurately weighed quantity of USP Salicylic Acid RS in Solvent mixture to obtain a solution having a known concentration of about 16 µg per mL.

Resolution solution— Dissolve salicylic acid in Aspirin and carisoprodol standard preparation to obtain a solution containing about 0.5 mg of salicylic acid per mL.

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. [NOTE—Use within 8 hours.]

Chromatographic system (see Chromatography 621)—The liquid chromatograph is equipped with a refractive index detector, a 313-nm detector, and a 4.6-mm × 25-cm column that contains packing L7. Maintain the refractive index detector and the column at 30 ± 1. The flow rate is about 1 mL per minute. Chromatograph the Aspirin and carisoprodol standard preparation and the Resolution solution, and record the peak responses as directed under Procedure, using the refractive index detector: the resolution, R, between the solvent and aspirin peaks in the chromatogram of the Resolution solution is not less than 1.2; the resolution, R, between the aspirin and salicylic acid peaks is not less than 1.5; and the relative standard deviation for replicate injections of the Aspirin and carisoprodol standard preparation is not more than 2.0%. Chromatograph the Salicylic acid standard preparation, and record the peak responses as directed for Procedure: the relative standard deviation for replicate injections is not more than 5.0%.

Procedure— Separately inject equal volumes (about 50 µL) of the Aspirin and carisoprodol standard preparation, the Salicylic acid standard preparation, and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks, using the refractive index detector for the Aspirin and carisoprodol standard preparation, the 313-nm detector for the Salicylic acid standard preparation, and both detectors for the Assay preparation. The relative retention times are about 0.6 for aspirin, 0.7 for salicylic acid, and 1.0 for carisoprodol. Calculate the quantity, in mg, of aspirin (C9H8O4) in the portion of Tablets taken by the formula: in which C is the concentration, in mg per mL, of USP Aspirin RS in the Aspirin and carisoprodol standard preparation; and rU and rS are the peak responses, with the use of the refractive index detector, obtained for aspirin from the Assay preparation and the Aspirin and carisoprodol standard preparation, respectively. Calculate the quantity, in mg, of carisoprodol (C12H24N2O4) in the portion of Tablets taken by the same formula, except to read “USP Carisoprodol RS” where “USP Aspirin RS” is specified, and “carisoprodol” where “aspirin” is specified. Calculate the percentage of free salicylic acid in the Tablets taken by the formula: in which C is the concentration, in µg per mL, of USP Salicylic Acid RS in the Salicylic acid standard preparation; a is the quantity, in mg, of aspirin in the portion of Tablets taken, based on the labeled amount; and rU and rS are the peak responses, with the use of the 313-nm detector, obtained for salicylic acid from the Assay preparation and the Salicylic acid standard preparation, respectively: not more than 3.0% is found.