Medium: water; 900 mL.

Apparatus 1: 100 rpm.

Time: 60 minutes.

Mobile phase and Chromatographic system—Prepare as directed in the Assay under Butalbital, Acetaminophen, and Caffeine Tablets.

Standard preparation— Prepare a solution in methanol having known concentrations of about 0.02A mg of USP Acetaminophen RS per mL, 0.02B mg of USP Butalbital RS per mL, and 0.02C mg of USP Caffeine RS per mL, in which A, B, and C are the labeled amounts, in mg of acetaminophen, butalbital, and caffeine, respectively, per Capsule. Transfer 5.0 mL of this solution to a 100-mL volumetric flask, dilute with water to volume, and mix.

Procedure— Pass a portion of the solution under test through a filter of 10-µm or finer porosity. Separately inject equal volumes (about 20 µL) of the filtrate and the Standard preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantities, in mg, of butalbital (C11H16N2O3), acetaminophen (C8H9NO2), and caffeine (C8H10N4O2) dissolved by the same formula: in which C is the concentration, in mg per mL, of the appropriate USP Reference Standard in the Standard preparation; and rU and rS are the peak responses of the corresponding analyte obtained from the solution under test and the Standard preparation, respectively.

Tolerances— Not less than 80% (Q) of the labeled amounts of C11H16N2O, C8H9NO2, and C8H10N4O2 is dissolved in 60 minutes.

Mobile phase, Internal standard solution, Butalbital standard stock solution, Caffeine standard stock solution, Standard preparation, and Chromatographic system— Proceed as directed in the Assay under Butalbital, Acetaminophen, and Caffeine Tablets.

Assay preparation— Remove, as completely as possible, the contents of not fewer than 20 Capsules. Transfer an accurately weighed portion of the powder, equivalent to about the weight of the contents of 1 Capsule, to a 200-mL volumetric flask, add Internal standard solution to volume, and mix. Sonicate for 15 minutes, mix, and allow to cool and settle. Transfer 20.0 mL of the clear supernatant to a 50-mL volumetric flask, dilute with water to volume, and mix. Pass a portion of this solution through a filter of 0.5 µm or finer porosity, discarding the first 5 mL of the filtrate. Use the clear filtrate as the Assay preparation.

Procedure— Separately inject equal volumes (about 10 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the peak responses for the major peaks. Calculate the quantities, in mg, of butalbital (C11H16N2O3), acetaminophen (C8H9NO2), and caffeine (C8H10N4O2) in the portion of Capsules taken by the formula: in which D is the concentration, in mg per mL, of the appropriate USP Reference Standard in the Standard preparation; and RU and RS are the peak response ratios of the corresponding analyte to phenacetin obtained from the Assay preparation and the Standard preparation, respectively.