Medium: water; 900 mL.

Apparatus 1: 100 rpm.

Time: 60 minutes.

Determination of dissolved butalbital—

Mobile phase —Prepare a suitable filtered and degassed mixture of water, acetonitrile, and phosphoric acid (3100:725:4). Adjust the ratio as necessary.

Standard preparation —Dissolve accurately weighed quantities of USP Butalbital RS and of salicylic acid in Mobile phase to obtain a solution containing known concentrations of about 1 µg of butalbital per mL for each mg of the labeled amount per Tablet and about 30 µg of salicylic acid per mL.

Chromatographic system (see Chromatography 621)—The liquid chromatograph is equipped with a 214-nm detector and a 3.9-mm × 30-cm column that contains 10-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 the butalbital and salicylic acid peaks is not less than 3.0; and the relative standard deviation of butalbital responses for replicate injections is not more than 3.0%.

Procedure —Filter a portion of the solution under test through a 0.5-µm filter. Separately inject equal volumes (about 10 to 25 µL) of the filtrate and the Standard preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. The relative retention times are about 0.6 for aspirin, 0.85 for salicylic acid, and 1.0 for butalbital. [note—After use, the column may be regenerated by passing through it at least 50 mL of a mixture of acetonitrile, methanol, and water (1:1:1), followed by 50 mL of a mixture of acetonitrile and water (1:1).] Calculate the amount, in mg, of butalbital (C11H16N2O3) dissolved by the formula: in which C is the concentration, in µg per mL, of USP Butalbital RS in the Standard preparation; and rU and rS are the butalbital peak responses obtained from the solution under test and the Standard preparation, respectively.

Determination of dissolved aspirin—

Tolerances— Not less than 75% (Q) of the labeled amounts of butalbital (C11H16N2O3) and aspirin (C9H8O4) are dissolved in 60 minutes.

Mobile phase— Prepare a suitable filtered and degassed mixture of water, acetonitrile, and phosphoric acid (3100:725:4). Adjust the ratio as necessary.

Solvent mixture— Mix 40 mL of formic acid and 4000 mL of acetonitrile.

Butalbital standard stock solution— Dissolve an accurately weighed quantity of USP Butalbital RS in Solvent mixture to obtain a solution having a known concentration of about 3250J µg per mL, J being the ratio of the labeled amount, in mg, of butalbital to the labeled amount, in mg, of aspirin per tablet.

Salicylic acid standard stock solution— Dissolve an accurately weighed quantity of USP Salicylic Acid RS in Solvent mixture to obtain a solution having a known concentration of about 200 µg per mL.

Butalbital and salicylic acid standard preparation— Transfer 25.0 mL of Butalbital standard stock solution and 3.0 mL of Salicylic acid standard stock solution to a 250-mL volumetric flask, dilute with Solvent mixture to volume, and mix. This solution contains about 325J µg of butalbital and 2.4 µg of salicylic acid per mL.

Aspirin standard preparation— Dissolve an accurately weighed quantity of USP Aspirin RS in Solvent mixture to obtain a solution having a known concentration of about 325 µg per mL.

Resolution solution— Transfer 4.0 mL of Butalbital standard stock solution and 3.0 mL of Salicylic acid standard stock solution to a 50-mL volumetric flask, 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 80 mg of aspirin, to a 250-mL volumetric flask, dilute with Solvent mixture to volume, sonicate for 15 minutes, and mix. Pass a portion of this solution through a 0.5-µm porosity filter before use.

Chromatographic system (see Chromatography 621)—The liquid chromatograph is equipped with a 214-nm detector and a 3.9-mm × 30-cm column that contains 10-µm packing L1. The flow rate is about 1.5 mL per minute. Chromatograph the Butalbital and salicylic acid standard preparation, the Aspirin standard preparation, and the Resolution solution as directed for Procedure: the resolution, R, between the butalbital and salicylic acid peaks is not less than 3.0; and the relative standard deviation for replicate injections of the Standard preparations is not more than 3.0% for butalbital and aspirin, and not more than 6.0% for salicylic acid.

Procedure— Separately inject equal volumes (about 10 µL) of the Standard preparations and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks, and for the minor peak corresponding to salicylic acid. The relative retention times are about 0.6 for aspirin, 0.85 for salicylic acid, and 1.0 for butalbital. [note—After use, the column may be regenerated by passing through it at least 50 mL of a mixture of acetonitrile, methanol, and water (1:1:1), followed by a mixture of acetonitrile and water (1:1).] Calculate the quantity, in mg, of butalbital (C11H16N2O3) in the portion of Tablets taken by the formula: in which C is the concentration, in µg per mL, of USP Butalbital RS in the Butalbital and salicylic acid standard preparation; and rU and rS are the butalbital peak responses obtained from the Assay preparation and the Butalbital and salicylic acid standard preparation, respectively. Calculate the quantity, in mg, of aspirin (C9H8O4) in the portion of Tablets taken by the formula: in which C is the concentration, in µg per mL, of USP Aspirin RS in the Aspirin standard preparation; and rU and rS are the aspirin peak responses obtained from the Assay preparation and the Aspirin standard preparation, respectively. 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 the USP Salicylic Acid RS in the Butalbital and 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 salicylic acid peak responses obtained from the Assay preparation and the Butalbital and salicylic acid standard preparation, respectively: not more than 3.0% is found.